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For MD-IQ on Family Practice News, but a regular topic for Rheumatology News
Positive trial of methotrexate in hand OA has modest results
Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.
Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.
Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.
The study was published online October 12 in The Lancet.
METHODS makes improvements on past studies
While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.
In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS.
Study details and results
METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.
The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.
The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.
The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.
The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).
MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study.
Qualifications and considerations for MTX use
Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.
Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.
She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.
“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.
Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”
Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”
In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.”
While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.
The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.
Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.
Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial).
The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.
Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.
Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.
The study was published online October 12 in The Lancet.
METHODS makes improvements on past studies
While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.
In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS.
Study details and results
METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.
The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.
The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.
The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.
The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).
MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study.
Qualifications and considerations for MTX use
Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.
Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.
She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.
“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.
Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”
Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”
In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.”
While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.
The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.
Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.
Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial).
The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.
Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.
Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.
The study was published online October 12 in The Lancet.
METHODS makes improvements on past studies
While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.
In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS.
Study details and results
METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.
The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.
The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.
The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.
The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).
MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study.
Qualifications and considerations for MTX use
Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.
Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.
She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.
“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.
Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”
Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”
In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.”
While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.
The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.
Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.
Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial).
The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET
New initiative aims to test investigational OA treatments in high-risk patients after knee injury
David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
FDA warns of hidden ingredients in arthritis, pain products
Some of these products contain active ingredients found in anti-inflammatory prescription medication.
“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”
Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.
From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.
Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.
“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”
Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.
These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.
The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
Advising patients
Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.
He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.
Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.
If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Tips for safe shopping
To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:
- Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
- Avoid buying products with labels in another language that you cannot read or products with no drug label.
- Be cautious of buying products online or from other countries.
- Look up suspicious products on the FDA’s health fraud database.
- Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.
In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.
Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.
Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.
Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.
“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”
Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Some of these products contain active ingredients found in anti-inflammatory prescription medication.
“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”
Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.
From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.
Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.
“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”
Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.
These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.
The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
Advising patients
Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.
He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.
Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.
If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Tips for safe shopping
To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:
- Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
- Avoid buying products with labels in another language that you cannot read or products with no drug label.
- Be cautious of buying products online or from other countries.
- Look up suspicious products on the FDA’s health fraud database.
- Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.
In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.
Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.
Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.
Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.
“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”
Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Some of these products contain active ingredients found in anti-inflammatory prescription medication.
“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”
Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.
From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.
Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.
“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”
Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.
These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.
The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
Advising patients
Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.
He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.
Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.
If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Tips for safe shopping
To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:
- Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
- Avoid buying products with labels in another language that you cannot read or products with no drug label.
- Be cautious of buying products online or from other countries.
- Look up suspicious products on the FDA’s health fraud database.
- Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.
In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.
Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.
Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.
Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.
“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”
Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Approximately 20% of U.S. adults are diagnosed with arthritis
TOPLINE:
The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.
METHODOLOGY:
- Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
- The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
- The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.
TAKEAWAY:
- Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
- Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
- When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
- The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.
IN PRACTICE:
“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.
SOURCE:
The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.
LIMITATIONS:
The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
TOPLINE:
The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.
METHODOLOGY:
- Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
- The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
- The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.
TAKEAWAY:
- Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
- Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
- When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
- The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.
IN PRACTICE:
“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.
SOURCE:
The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.
LIMITATIONS:
The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
TOPLINE:
The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.
METHODOLOGY:
- Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
- The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
- The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.
TAKEAWAY:
- Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
- Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
- When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
- The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.
IN PRACTICE:
“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.
SOURCE:
The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.
LIMITATIONS:
The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Osteoarthritis cases projected to balloon over next 30 years
TOPLINE:
METHODOLOGY:
- Researchers estimated the prevalence of osteoarthritis in 204 countries and territories from 1990 to 2020 and projected prevalence levels for the year 2050.
- Population-based surveys offered data from 26 countries for knee osteoarthritis, 23 countries for hip osteoarthritis, and 42 countries for hand osteoarthritis. Researchers used U.S. insurance claims to estimate prevalence for other osteoarthritis types.
- Similar analyses were conducted in 2010 and 2017.
TAKEAWAY:
- Osteoarthritis cases worldwide have grown by an estimated 132.2% since 1990. Population growth and aging were identified as major contributing factors.
- In 2020, an estimated 595 million people had osteoarthritis. From 2020 to 2050, cases of osteoarthritis in the knee are expected to grow by 74.9%, in the hand by 48.6%, in the hip by 78.6%, and in other locations by 95.1%.
- Years lived with disability (age-standardized rate) grew from an estimated 233 per 100,000 in 1990 to 255 per 100,000 in 2020, an increase of 9.5%.
- High body mass index contributed to 20.4% of cases.
IN PRACTICE:
In “a major challenge to health systems,” osteoarthritis may affect nearly 1 billion people in 2050.
SOURCE:
The Global Burden of Disease 2021 Osteoarthritis Collaborators, led by Jaimie D. Steinmetz, PhD, MSc, of the Institute for Health Metrics and Evaluation, Seattle, conducted the study, which was published in The Lancet Rheumatology.
LIMITATIONS:
Limited data, heavy reliance on U.S. insurance data, and other factors may have skewed the results.
DISCLOSURES:
The study was supported by the Bill & Melinda Gates Foundation, the Institute of Bone and Joint Research, and the Global Alliance for Musculoskeletal Health. Multiple authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers estimated the prevalence of osteoarthritis in 204 countries and territories from 1990 to 2020 and projected prevalence levels for the year 2050.
- Population-based surveys offered data from 26 countries for knee osteoarthritis, 23 countries for hip osteoarthritis, and 42 countries for hand osteoarthritis. Researchers used U.S. insurance claims to estimate prevalence for other osteoarthritis types.
- Similar analyses were conducted in 2010 and 2017.
TAKEAWAY:
- Osteoarthritis cases worldwide have grown by an estimated 132.2% since 1990. Population growth and aging were identified as major contributing factors.
- In 2020, an estimated 595 million people had osteoarthritis. From 2020 to 2050, cases of osteoarthritis in the knee are expected to grow by 74.9%, in the hand by 48.6%, in the hip by 78.6%, and in other locations by 95.1%.
- Years lived with disability (age-standardized rate) grew from an estimated 233 per 100,000 in 1990 to 255 per 100,000 in 2020, an increase of 9.5%.
- High body mass index contributed to 20.4% of cases.
IN PRACTICE:
In “a major challenge to health systems,” osteoarthritis may affect nearly 1 billion people in 2050.
SOURCE:
The Global Burden of Disease 2021 Osteoarthritis Collaborators, led by Jaimie D. Steinmetz, PhD, MSc, of the Institute for Health Metrics and Evaluation, Seattle, conducted the study, which was published in The Lancet Rheumatology.
LIMITATIONS:
Limited data, heavy reliance on U.S. insurance data, and other factors may have skewed the results.
DISCLOSURES:
The study was supported by the Bill & Melinda Gates Foundation, the Institute of Bone and Joint Research, and the Global Alliance for Musculoskeletal Health. Multiple authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers estimated the prevalence of osteoarthritis in 204 countries and territories from 1990 to 2020 and projected prevalence levels for the year 2050.
- Population-based surveys offered data from 26 countries for knee osteoarthritis, 23 countries for hip osteoarthritis, and 42 countries for hand osteoarthritis. Researchers used U.S. insurance claims to estimate prevalence for other osteoarthritis types.
- Similar analyses were conducted in 2010 and 2017.
TAKEAWAY:
- Osteoarthritis cases worldwide have grown by an estimated 132.2% since 1990. Population growth and aging were identified as major contributing factors.
- In 2020, an estimated 595 million people had osteoarthritis. From 2020 to 2050, cases of osteoarthritis in the knee are expected to grow by 74.9%, in the hand by 48.6%, in the hip by 78.6%, and in other locations by 95.1%.
- Years lived with disability (age-standardized rate) grew from an estimated 233 per 100,000 in 1990 to 255 per 100,000 in 2020, an increase of 9.5%.
- High body mass index contributed to 20.4% of cases.
IN PRACTICE:
In “a major challenge to health systems,” osteoarthritis may affect nearly 1 billion people in 2050.
SOURCE:
The Global Burden of Disease 2021 Osteoarthritis Collaborators, led by Jaimie D. Steinmetz, PhD, MSc, of the Institute for Health Metrics and Evaluation, Seattle, conducted the study, which was published in The Lancet Rheumatology.
LIMITATIONS:
Limited data, heavy reliance on U.S. insurance data, and other factors may have skewed the results.
DISCLOSURES:
The study was supported by the Bill & Melinda Gates Foundation, the Institute of Bone and Joint Research, and the Global Alliance for Musculoskeletal Health. Multiple authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
FROM THE LANCET RHEUMATOLOGY
Could GLP-1 receptor agonists ease knee osteoarthritis pain, slow progression?
Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?
Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.
Three recently published studies investigated this:
- The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
- A large observational study out of China in patients with KOA and type 2 diabetes.
- A preclinical trial of liraglutide in mouse models of KOA.
The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.
This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
The big picture, as seen by two experts
The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.
Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.
Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.
“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.
Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”
Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.
Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.
Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.
“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.
They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.
He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
Three published studies
LOSEIT: RCT of liraglutide for pain and weight control in KOA
Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.
All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.
Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.
From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.
“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.
“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”
The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.
“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.
Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.
The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.
Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”
Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.
In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
Observational study of patients with diabetes and KOA
Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.
They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.
The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m2, and a mean A1c of 7.3%.
“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.
The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).
Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.
“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.
They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”
They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.
Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m2 and has osteoarthritis, he or she could still benefit from weight loss, he said.
Liraglutide and pain-related behavior in mouse models of OA
Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.
In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.
The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).
They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.
“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”
Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
Two trials near completion, one is upcoming
Phase 1 and 2 trials of 4P-004
“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.
The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.
The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
Phase 3 trial of semaglutide for KOA
Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.
Eligible patients were aged 18 and older, with BMI > 30 kg/m2 and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.
The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.
Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?
Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.
Three recently published studies investigated this:
- The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
- A large observational study out of China in patients with KOA and type 2 diabetes.
- A preclinical trial of liraglutide in mouse models of KOA.
The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.
This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
The big picture, as seen by two experts
The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.
Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.
Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.
“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.
Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”
Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.
Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.
Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.
“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.
They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.
He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
Three published studies
LOSEIT: RCT of liraglutide for pain and weight control in KOA
Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.
All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.
Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.
From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.
“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.
“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”
The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.
“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.
Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.
The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.
Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”
Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.
In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
Observational study of patients with diabetes and KOA
Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.
They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.
The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m2, and a mean A1c of 7.3%.
“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.
The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).
Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.
“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.
They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”
They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.
Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m2 and has osteoarthritis, he or she could still benefit from weight loss, he said.
Liraglutide and pain-related behavior in mouse models of OA
Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.
In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.
The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).
They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.
“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”
Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
Two trials near completion, one is upcoming
Phase 1 and 2 trials of 4P-004
“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.
The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.
The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
Phase 3 trial of semaglutide for KOA
Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.
Eligible patients were aged 18 and older, with BMI > 30 kg/m2 and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.
The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.
Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?
Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.
Three recently published studies investigated this:
- The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
- A large observational study out of China in patients with KOA and type 2 diabetes.
- A preclinical trial of liraglutide in mouse models of KOA.
The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.
This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
The big picture, as seen by two experts
The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.
Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.
Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.
“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.
Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”
Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.
Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.
Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.
“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.
They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.
He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
Three published studies
LOSEIT: RCT of liraglutide for pain and weight control in KOA
Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.
All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.
Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.
From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.
“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.
“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”
The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.
“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.
Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.
The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.
Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”
Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.
In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
Observational study of patients with diabetes and KOA
Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.
They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.
The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m2, and a mean A1c of 7.3%.
“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.
The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).
Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.
“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.
They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”
They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.
Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m2 and has osteoarthritis, he or she could still benefit from weight loss, he said.
Liraglutide and pain-related behavior in mouse models of OA
Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.
In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.
The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).
They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.
“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”
Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
Two trials near completion, one is upcoming
Phase 1 and 2 trials of 4P-004
“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.
The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.
The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
Phase 3 trial of semaglutide for KOA
Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.
Eligible patients were aged 18 and older, with BMI > 30 kg/m2 and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.
The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.
Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
A version of this article appeared on Medscape.com.
New clues arise to consequences of calcium crystal deposition in knee OA
Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.
Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.
The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”
In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”
The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
Study details
Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m2. In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.
Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
Perspective
“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.
Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.
“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.
The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
Could colchicine help?
In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.
The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
Independent perspective
The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.
The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.
As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
Takeaways
Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?
Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.
Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”
On one point all agreed: More research is needed.
Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.
Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.
Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.
The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”
In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”
The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
Study details
Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m2. In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.
Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
Perspective
“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.
Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.
“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.
The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
Could colchicine help?
In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.
The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
Independent perspective
The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.
The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.
As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
Takeaways
Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?
Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.
Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”
On one point all agreed: More research is needed.
Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.
Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.
Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.
The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”
In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”
The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
Study details
Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m2. In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.
Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
Perspective
“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.
Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.
“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.
The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
Could colchicine help?
In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.
The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
Independent perspective
The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.
The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.
As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
Takeaways
Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?
Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.
Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”
On one point all agreed: More research is needed.
Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.
FROM ARTHRITIS & RHEUMATOLOGY
Exercise and empathy can help back pain patients in primary care
Treatment of chronic back pain remains a challenge for primary care physicians, and a new Cochrane Review confirms previous studies suggesting that analgesics and antidepressants fall short in terms of relief.
Data from another Cochrane Review support the value of exercise for chronic low back pain, although it is often underused, and the Food and Drug Administration’s recent approval of a spinal cord stimulation device for chronic back pain opens the door for another alternative.
Regardless of treatment type, however, patients report that empathy and clear communication from their doctors go a long way in their satisfaction with pain management, according to another recent study.
Exercise helps when patients adhere
The objective of the Cochrane Review on “Exercise therapy for chronic low back pain” was to determine whether exercise improves pain and functioning for people with chronic low back pain, compared with no treatment, usual care, or other common treatments, corresponding author Jill Hayden, PhD, of Dalhousie University, Halifax, N.S., said in an interview.
When back pain is chronic, it is expensive in terms of health care costs and lost work hours, said Dr. Hayden. “Exercise is promoted in many guidelines and is often recommended for, and used by, people with chronic low back pain.” However, “systematic reviews have found only small treatment effects, with considerable variation across individual trials.”
The 2021 review is one of the largest in the Cochrane Library, and included 249 trials and 24,486 study participants. However, Dr. Hayden said she had been disappointed by the methodological limitations of many of the trials. “The field is saturated with small exercise trials, many of which suffer from poor planning, conduct, and reporting due to limited resources.”
In the current review, “we found that exercise is likely to be effective for chronic low back pain. Overall, 3 months after the start of treatment, people receiving exercise treatment rated their pain an average of 15 points better on a scale of 0-100, and functional limitations were 7 points better, compared to people who had no treatment or usual care,” said Dr. Hayden.
Barriers to the use of exercise to treat pain may include fear of movement on the part of patients, she noted.
“Although our related network meta-analysis found some differences between specific types of exercise, we found all exercise types are more effective than minimal treatment,” she said. “People with chronic low back pain should be encouraged to do exercises that they enjoy and will do consistently to promote adherence.”
Limitations of medications
Both the safety and effectiveness of analgesics and antidepressants for pain in general and back pain in particular have come under scrutiny in recent research. A study published online in the British Medical Journal of patients with acute low back pain found that, although some medications were associated with large reductions in pain intensity, compared with placebo, the quality of the studies was “low or very low confidence,” according to a Medscape report on the findings.
This conclusion was supported in a large-scale analysis of the safety and effectiveness of antidepressants in chronic pain conditions, including back pain.
A new Cochrane Review led by a team of researchers in the United Kingdom found inadequate evidence to support the effectiveness of most antidepressants used for chronic pain, including amitriptyline, fluoxetine, citalopram, paroxetine, sertraline, and duloxetine.
“While chronic pain remains one of the top causes of daily disability worldwide, clinicians’ choices at offering interventions are getting fewer, especially if they tend toward a medical model and want a pharmacological solution,” corresponding author Tamar Pincus, PhD, of the University of Southampton (England), said in an interview. “We now know that opioids harm patients, and the evidence for common analgesics such as paracetamol and ibuprofen, for some conditions such as back pain, suggest they are not effective and might cause harm. This leaves clinicians with few options, and the most common prescription, supported by guidelines, is antidepressants.”
The study found moderate evidence that duloxetine can reduce pain in the short term and improve physical activity and some evidence that milnacipran might also be effective, Dr. Pincus said. “For all other antidepressants, including the commonly prescribed amitriptyline, the evidence was poor. Of importance, the average length of trials was 10 weeks, so long-term effects for all antidepressants remain unknown, and side effects and adverse events were reported poorly, so we also don’t know if any antidepressants are harmful.”
The takeaway message for the management of back pain in particular? “If a clinician and a patient decide together that it would be a good idea to try an antidepressant to reduce pain, they should consider starting with duloxetine, the drug with supporting evidence,” she said.
Physician attitude matters
Antidepressants may not have much impact on chronic pain, but a physician’s empathy and support do, according to data from a registry study of more than 1,300 individuals.
Despite efforts and guidelines from multiple medical organizations to promote optimal pain management, “much remains unknown regarding how the patient-physician interaction affects the process of delivering medical care for chronic low back pain and, ultimately, patient satisfaction,” John C. Licciardone, DO, of the University of North Texas Health Science Center, Fort Worth, and colleagues wrote in Annals of Family Medicine.
Previous studies have examined the relationship between clinical outcomes and patient satisfaction, but data on patient satisfaction with medical care for chronic low back pain specifically are limited, they said.
The researchers reviewed data from a national pain registry of adults aged 21-79 years that included self-reported measures of physician communication and empathy, prescribing data for opioids, and outcomes data for pain intensity, physical function, and health-related quality of life.
In a multivariate analysis, physician empathy and physician communication showed the strongest associations with patient satisfaction (P < .001).
The researchers found a negligible correlation between opioid prescription and perceived physician empathy and communication, “although current physician prescribing of opioids was also associated with patient satisfaction,” they wrote.
“Our findings pertaining to physician empathy are intriguing because they do not necessarily involve a therapeutic alliance with the patient based on collaborative communication or the expectation of a therapeutic effect via pharmacotherapy,” the researchers wrote .
The findings were limited by several factors including the cross-sectional design that prevented conclusions about cause and effect, the researchers noted. “It is possible that prior improvements in pain intensity, physical function, or [health-related quality of life] might have prompted participants to report more favorable ratings for physician empathy, physician communication, or patient satisfaction at registry enrollment.” However, the study supports the view that patients with low back pain in particular value physicians who validate their concerns and symptoms, and who make an effort to communicate treatment plans clearly.
Back pain patients continue to challenge primary care
“Back pain is a major issue in U.S. health care, in part because too many people have tough physical jobs or longstanding injuries that become chronic,” William Golden, MD, professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock, said in an interview.
“There are no magic bullets for a lot of back pain patients, so empathy and support are key drivers,” he noted. “Helping patients maximize functionality as opposed to seeking mythical cures is the stronger line of visit discussions, but that takes a bit of time and skill in interviewing.
“It is fairly well established that duloxetine is useful in pain management, especially when present with mood disorders, either primary or secondary to the back-related disability,” said Dr. Golden. “Greater dissemination of its utility is probably useful, as is the side effect profile of the drug as well,” given the “nasty discontinuation syndrome when the treatment is reduced or stopped.”
Looking ahead, “more research is needed about microsurgery, namely for whom and for what anatomic presentations,” said Dr. Golden. Other topics for further research include a better understanding about medical marijuana and pain management and its interactions and side effects with other opioids and muscle relaxants. “Polypharmacy is still an issue in this class of patient,” and many of these patients are frustrated and angry “so the psychosocial skills of the PCP can be greatly tested as well,” he said.
Empathy promotes patient adherence to treatment
The new opioid prescription guidelines have increased interest among clinicians in how to improve patient satisfaction with the care for back pain provided, Noel Deep, MD, said in an interview. “These studies address this concern and bring forth an important aspect of the physician-patient relationship, namely the human touch and empathy.”
“I have been a strong proponent of the trust and relationship between a physician and patient; displaying empathy and increased and transparent communication between the physician and the patient has always resulted in better relationships and better outcomes for patients, especially those dealing with chronic health concerns,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.
Potential barriers to effective pain management include beliefs and attitudes on the part of patients, Dr. Deep noted. “Physicians lacking adequate time to communicate effectively with the patient and describe nonopioid and nonsurgical interventions would be another potential barrier.” Other issues include the time and effort, as well as cost, associated with interventions such as physical therapy and other nondrug and nonsurgical interventions. Issues with family and social support and health literacy are also potential barriers to pain management.
Clinical takeaways
Low back pain is one of the most common reasons for a visit in primary care and can be “chronic and debilitating,” Grace Lin, MD, an internal medicine physician and primary care provider at the University of California, San Francisco, said in an interview.
“One issue with the Cochrane Review on exercise is that the studies on exercise were heterogeneous, so it’s difficult to know whether there is a particular kind of exercise that would be most effective and should be recommended to patients,” she said.
Furthermore, she said, “there is a physical therapist shortage in the U.S. I practice in a major city with a large health care system, and it can still take months to get an appointment with a physical therapist.” Also, insurance coverage may limit which therapists a patient can see and how many visits they can have.
“On the clinician side, I think physicians need to be better informed about the evidence base for back pain treatment, namely that exercise is effective and that, long term, analgesics are not,” Dr. Lin said. “This might decrease overprescription of ineffective analgesics and encourage more education about and referrals to physical therapy.”
“Physicians should continue to educate patients that physical therapy is the first-line treatment for back pain and that pain medications are secondary,” she said. “I think that analgesics can be effective for the short term to get people to a point where they feel well enough to do physical therapy. Duloxetine also appears to be moderately effective for chronic low back pain, in part because it may also help address coexisting depression and anxiety,” but these options should be reserved for adjuncts to physical therapy for back pain.
The findings from the study on empathy and communication suggest that the main challenges to these behaviors are systemic, said Dr. Lin.
“Our health care system is not conducive to treating chronic back pain,” she said. Primary care visits that last for 15 or 20 minutes are not long enough to diagnose and counsel patients on such a complex problem as chronic low back pain. Since back pain is usually not the only issue the primary care physician is dealing with during that visit, this can lead to patients feeling like their doctor isn’t listening to them and doesn’t care about their pain.
“We need to better understand the mechanisms by which people develop chronic, debilitating back pain,” Dr. Lin said. “I think if we understood this better, more effective and targeted treatments, both pharmacological and nonpharmacological, could be developed.”
The Annals of Family Medicine study received no outside funding, and the researchers had no financial conflicts to disclose. The Cochrane Reviews was supported by the National Institute for Health and Care Research’s Health Technology Assessment program, and the authors had no financial conflicts to disclose. Dr. Golden and Dr. Deep had no financial conflicts to disclose and serve on the editorial advisory board of Internal Medicine News. Dr. Lin disclosed receiving research funding from the Institute for Clinical and Economic Review and the National Institutes of Health.
Treatment of chronic back pain remains a challenge for primary care physicians, and a new Cochrane Review confirms previous studies suggesting that analgesics and antidepressants fall short in terms of relief.
Data from another Cochrane Review support the value of exercise for chronic low back pain, although it is often underused, and the Food and Drug Administration’s recent approval of a spinal cord stimulation device for chronic back pain opens the door for another alternative.
Regardless of treatment type, however, patients report that empathy and clear communication from their doctors go a long way in their satisfaction with pain management, according to another recent study.
Exercise helps when patients adhere
The objective of the Cochrane Review on “Exercise therapy for chronic low back pain” was to determine whether exercise improves pain and functioning for people with chronic low back pain, compared with no treatment, usual care, or other common treatments, corresponding author Jill Hayden, PhD, of Dalhousie University, Halifax, N.S., said in an interview.
When back pain is chronic, it is expensive in terms of health care costs and lost work hours, said Dr. Hayden. “Exercise is promoted in many guidelines and is often recommended for, and used by, people with chronic low back pain.” However, “systematic reviews have found only small treatment effects, with considerable variation across individual trials.”
The 2021 review is one of the largest in the Cochrane Library, and included 249 trials and 24,486 study participants. However, Dr. Hayden said she had been disappointed by the methodological limitations of many of the trials. “The field is saturated with small exercise trials, many of which suffer from poor planning, conduct, and reporting due to limited resources.”
In the current review, “we found that exercise is likely to be effective for chronic low back pain. Overall, 3 months after the start of treatment, people receiving exercise treatment rated their pain an average of 15 points better on a scale of 0-100, and functional limitations were 7 points better, compared to people who had no treatment or usual care,” said Dr. Hayden.
Barriers to the use of exercise to treat pain may include fear of movement on the part of patients, she noted.
“Although our related network meta-analysis found some differences between specific types of exercise, we found all exercise types are more effective than minimal treatment,” she said. “People with chronic low back pain should be encouraged to do exercises that they enjoy and will do consistently to promote adherence.”
Limitations of medications
Both the safety and effectiveness of analgesics and antidepressants for pain in general and back pain in particular have come under scrutiny in recent research. A study published online in the British Medical Journal of patients with acute low back pain found that, although some medications were associated with large reductions in pain intensity, compared with placebo, the quality of the studies was “low or very low confidence,” according to a Medscape report on the findings.
This conclusion was supported in a large-scale analysis of the safety and effectiveness of antidepressants in chronic pain conditions, including back pain.
A new Cochrane Review led by a team of researchers in the United Kingdom found inadequate evidence to support the effectiveness of most antidepressants used for chronic pain, including amitriptyline, fluoxetine, citalopram, paroxetine, sertraline, and duloxetine.
“While chronic pain remains one of the top causes of daily disability worldwide, clinicians’ choices at offering interventions are getting fewer, especially if they tend toward a medical model and want a pharmacological solution,” corresponding author Tamar Pincus, PhD, of the University of Southampton (England), said in an interview. “We now know that opioids harm patients, and the evidence for common analgesics such as paracetamol and ibuprofen, for some conditions such as back pain, suggest they are not effective and might cause harm. This leaves clinicians with few options, and the most common prescription, supported by guidelines, is antidepressants.”
The study found moderate evidence that duloxetine can reduce pain in the short term and improve physical activity and some evidence that milnacipran might also be effective, Dr. Pincus said. “For all other antidepressants, including the commonly prescribed amitriptyline, the evidence was poor. Of importance, the average length of trials was 10 weeks, so long-term effects for all antidepressants remain unknown, and side effects and adverse events were reported poorly, so we also don’t know if any antidepressants are harmful.”
The takeaway message for the management of back pain in particular? “If a clinician and a patient decide together that it would be a good idea to try an antidepressant to reduce pain, they should consider starting with duloxetine, the drug with supporting evidence,” she said.
Physician attitude matters
Antidepressants may not have much impact on chronic pain, but a physician’s empathy and support do, according to data from a registry study of more than 1,300 individuals.
Despite efforts and guidelines from multiple medical organizations to promote optimal pain management, “much remains unknown regarding how the patient-physician interaction affects the process of delivering medical care for chronic low back pain and, ultimately, patient satisfaction,” John C. Licciardone, DO, of the University of North Texas Health Science Center, Fort Worth, and colleagues wrote in Annals of Family Medicine.
Previous studies have examined the relationship between clinical outcomes and patient satisfaction, but data on patient satisfaction with medical care for chronic low back pain specifically are limited, they said.
The researchers reviewed data from a national pain registry of adults aged 21-79 years that included self-reported measures of physician communication and empathy, prescribing data for opioids, and outcomes data for pain intensity, physical function, and health-related quality of life.
In a multivariate analysis, physician empathy and physician communication showed the strongest associations with patient satisfaction (P < .001).
The researchers found a negligible correlation between opioid prescription and perceived physician empathy and communication, “although current physician prescribing of opioids was also associated with patient satisfaction,” they wrote.
“Our findings pertaining to physician empathy are intriguing because they do not necessarily involve a therapeutic alliance with the patient based on collaborative communication or the expectation of a therapeutic effect via pharmacotherapy,” the researchers wrote .
The findings were limited by several factors including the cross-sectional design that prevented conclusions about cause and effect, the researchers noted. “It is possible that prior improvements in pain intensity, physical function, or [health-related quality of life] might have prompted participants to report more favorable ratings for physician empathy, physician communication, or patient satisfaction at registry enrollment.” However, the study supports the view that patients with low back pain in particular value physicians who validate their concerns and symptoms, and who make an effort to communicate treatment plans clearly.
Back pain patients continue to challenge primary care
“Back pain is a major issue in U.S. health care, in part because too many people have tough physical jobs or longstanding injuries that become chronic,” William Golden, MD, professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock, said in an interview.
“There are no magic bullets for a lot of back pain patients, so empathy and support are key drivers,” he noted. “Helping patients maximize functionality as opposed to seeking mythical cures is the stronger line of visit discussions, but that takes a bit of time and skill in interviewing.
“It is fairly well established that duloxetine is useful in pain management, especially when present with mood disorders, either primary or secondary to the back-related disability,” said Dr. Golden. “Greater dissemination of its utility is probably useful, as is the side effect profile of the drug as well,” given the “nasty discontinuation syndrome when the treatment is reduced or stopped.”
Looking ahead, “more research is needed about microsurgery, namely for whom and for what anatomic presentations,” said Dr. Golden. Other topics for further research include a better understanding about medical marijuana and pain management and its interactions and side effects with other opioids and muscle relaxants. “Polypharmacy is still an issue in this class of patient,” and many of these patients are frustrated and angry “so the psychosocial skills of the PCP can be greatly tested as well,” he said.
Empathy promotes patient adherence to treatment
The new opioid prescription guidelines have increased interest among clinicians in how to improve patient satisfaction with the care for back pain provided, Noel Deep, MD, said in an interview. “These studies address this concern and bring forth an important aspect of the physician-patient relationship, namely the human touch and empathy.”
“I have been a strong proponent of the trust and relationship between a physician and patient; displaying empathy and increased and transparent communication between the physician and the patient has always resulted in better relationships and better outcomes for patients, especially those dealing with chronic health concerns,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.
Potential barriers to effective pain management include beliefs and attitudes on the part of patients, Dr. Deep noted. “Physicians lacking adequate time to communicate effectively with the patient and describe nonopioid and nonsurgical interventions would be another potential barrier.” Other issues include the time and effort, as well as cost, associated with interventions such as physical therapy and other nondrug and nonsurgical interventions. Issues with family and social support and health literacy are also potential barriers to pain management.
Clinical takeaways
Low back pain is one of the most common reasons for a visit in primary care and can be “chronic and debilitating,” Grace Lin, MD, an internal medicine physician and primary care provider at the University of California, San Francisco, said in an interview.
“One issue with the Cochrane Review on exercise is that the studies on exercise were heterogeneous, so it’s difficult to know whether there is a particular kind of exercise that would be most effective and should be recommended to patients,” she said.
Furthermore, she said, “there is a physical therapist shortage in the U.S. I practice in a major city with a large health care system, and it can still take months to get an appointment with a physical therapist.” Also, insurance coverage may limit which therapists a patient can see and how many visits they can have.
“On the clinician side, I think physicians need to be better informed about the evidence base for back pain treatment, namely that exercise is effective and that, long term, analgesics are not,” Dr. Lin said. “This might decrease overprescription of ineffective analgesics and encourage more education about and referrals to physical therapy.”
“Physicians should continue to educate patients that physical therapy is the first-line treatment for back pain and that pain medications are secondary,” she said. “I think that analgesics can be effective for the short term to get people to a point where they feel well enough to do physical therapy. Duloxetine also appears to be moderately effective for chronic low back pain, in part because it may also help address coexisting depression and anxiety,” but these options should be reserved for adjuncts to physical therapy for back pain.
The findings from the study on empathy and communication suggest that the main challenges to these behaviors are systemic, said Dr. Lin.
“Our health care system is not conducive to treating chronic back pain,” she said. Primary care visits that last for 15 or 20 minutes are not long enough to diagnose and counsel patients on such a complex problem as chronic low back pain. Since back pain is usually not the only issue the primary care physician is dealing with during that visit, this can lead to patients feeling like their doctor isn’t listening to them and doesn’t care about their pain.
“We need to better understand the mechanisms by which people develop chronic, debilitating back pain,” Dr. Lin said. “I think if we understood this better, more effective and targeted treatments, both pharmacological and nonpharmacological, could be developed.”
The Annals of Family Medicine study received no outside funding, and the researchers had no financial conflicts to disclose. The Cochrane Reviews was supported by the National Institute for Health and Care Research’s Health Technology Assessment program, and the authors had no financial conflicts to disclose. Dr. Golden and Dr. Deep had no financial conflicts to disclose and serve on the editorial advisory board of Internal Medicine News. Dr. Lin disclosed receiving research funding from the Institute for Clinical and Economic Review and the National Institutes of Health.
Treatment of chronic back pain remains a challenge for primary care physicians, and a new Cochrane Review confirms previous studies suggesting that analgesics and antidepressants fall short in terms of relief.
Data from another Cochrane Review support the value of exercise for chronic low back pain, although it is often underused, and the Food and Drug Administration’s recent approval of a spinal cord stimulation device for chronic back pain opens the door for another alternative.
Regardless of treatment type, however, patients report that empathy and clear communication from their doctors go a long way in their satisfaction with pain management, according to another recent study.
Exercise helps when patients adhere
The objective of the Cochrane Review on “Exercise therapy for chronic low back pain” was to determine whether exercise improves pain and functioning for people with chronic low back pain, compared with no treatment, usual care, or other common treatments, corresponding author Jill Hayden, PhD, of Dalhousie University, Halifax, N.S., said in an interview.
When back pain is chronic, it is expensive in terms of health care costs and lost work hours, said Dr. Hayden. “Exercise is promoted in many guidelines and is often recommended for, and used by, people with chronic low back pain.” However, “systematic reviews have found only small treatment effects, with considerable variation across individual trials.”
The 2021 review is one of the largest in the Cochrane Library, and included 249 trials and 24,486 study participants. However, Dr. Hayden said she had been disappointed by the methodological limitations of many of the trials. “The field is saturated with small exercise trials, many of which suffer from poor planning, conduct, and reporting due to limited resources.”
In the current review, “we found that exercise is likely to be effective for chronic low back pain. Overall, 3 months after the start of treatment, people receiving exercise treatment rated their pain an average of 15 points better on a scale of 0-100, and functional limitations were 7 points better, compared to people who had no treatment or usual care,” said Dr. Hayden.
Barriers to the use of exercise to treat pain may include fear of movement on the part of patients, she noted.
“Although our related network meta-analysis found some differences between specific types of exercise, we found all exercise types are more effective than minimal treatment,” she said. “People with chronic low back pain should be encouraged to do exercises that they enjoy and will do consistently to promote adherence.”
Limitations of medications
Both the safety and effectiveness of analgesics and antidepressants for pain in general and back pain in particular have come under scrutiny in recent research. A study published online in the British Medical Journal of patients with acute low back pain found that, although some medications were associated with large reductions in pain intensity, compared with placebo, the quality of the studies was “low or very low confidence,” according to a Medscape report on the findings.
This conclusion was supported in a large-scale analysis of the safety and effectiveness of antidepressants in chronic pain conditions, including back pain.
A new Cochrane Review led by a team of researchers in the United Kingdom found inadequate evidence to support the effectiveness of most antidepressants used for chronic pain, including amitriptyline, fluoxetine, citalopram, paroxetine, sertraline, and duloxetine.
“While chronic pain remains one of the top causes of daily disability worldwide, clinicians’ choices at offering interventions are getting fewer, especially if they tend toward a medical model and want a pharmacological solution,” corresponding author Tamar Pincus, PhD, of the University of Southampton (England), said in an interview. “We now know that opioids harm patients, and the evidence for common analgesics such as paracetamol and ibuprofen, for some conditions such as back pain, suggest they are not effective and might cause harm. This leaves clinicians with few options, and the most common prescription, supported by guidelines, is antidepressants.”
The study found moderate evidence that duloxetine can reduce pain in the short term and improve physical activity and some evidence that milnacipran might also be effective, Dr. Pincus said. “For all other antidepressants, including the commonly prescribed amitriptyline, the evidence was poor. Of importance, the average length of trials was 10 weeks, so long-term effects for all antidepressants remain unknown, and side effects and adverse events were reported poorly, so we also don’t know if any antidepressants are harmful.”
The takeaway message for the management of back pain in particular? “If a clinician and a patient decide together that it would be a good idea to try an antidepressant to reduce pain, they should consider starting with duloxetine, the drug with supporting evidence,” she said.
Physician attitude matters
Antidepressants may not have much impact on chronic pain, but a physician’s empathy and support do, according to data from a registry study of more than 1,300 individuals.
Despite efforts and guidelines from multiple medical organizations to promote optimal pain management, “much remains unknown regarding how the patient-physician interaction affects the process of delivering medical care for chronic low back pain and, ultimately, patient satisfaction,” John C. Licciardone, DO, of the University of North Texas Health Science Center, Fort Worth, and colleagues wrote in Annals of Family Medicine.
Previous studies have examined the relationship between clinical outcomes and patient satisfaction, but data on patient satisfaction with medical care for chronic low back pain specifically are limited, they said.
The researchers reviewed data from a national pain registry of adults aged 21-79 years that included self-reported measures of physician communication and empathy, prescribing data for opioids, and outcomes data for pain intensity, physical function, and health-related quality of life.
In a multivariate analysis, physician empathy and physician communication showed the strongest associations with patient satisfaction (P < .001).
The researchers found a negligible correlation between opioid prescription and perceived physician empathy and communication, “although current physician prescribing of opioids was also associated with patient satisfaction,” they wrote.
“Our findings pertaining to physician empathy are intriguing because they do not necessarily involve a therapeutic alliance with the patient based on collaborative communication or the expectation of a therapeutic effect via pharmacotherapy,” the researchers wrote .
The findings were limited by several factors including the cross-sectional design that prevented conclusions about cause and effect, the researchers noted. “It is possible that prior improvements in pain intensity, physical function, or [health-related quality of life] might have prompted participants to report more favorable ratings for physician empathy, physician communication, or patient satisfaction at registry enrollment.” However, the study supports the view that patients with low back pain in particular value physicians who validate their concerns and symptoms, and who make an effort to communicate treatment plans clearly.
Back pain patients continue to challenge primary care
“Back pain is a major issue in U.S. health care, in part because too many people have tough physical jobs or longstanding injuries that become chronic,” William Golden, MD, professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock, said in an interview.
“There are no magic bullets for a lot of back pain patients, so empathy and support are key drivers,” he noted. “Helping patients maximize functionality as opposed to seeking mythical cures is the stronger line of visit discussions, but that takes a bit of time and skill in interviewing.
“It is fairly well established that duloxetine is useful in pain management, especially when present with mood disorders, either primary or secondary to the back-related disability,” said Dr. Golden. “Greater dissemination of its utility is probably useful, as is the side effect profile of the drug as well,” given the “nasty discontinuation syndrome when the treatment is reduced or stopped.”
Looking ahead, “more research is needed about microsurgery, namely for whom and for what anatomic presentations,” said Dr. Golden. Other topics for further research include a better understanding about medical marijuana and pain management and its interactions and side effects with other opioids and muscle relaxants. “Polypharmacy is still an issue in this class of patient,” and many of these patients are frustrated and angry “so the psychosocial skills of the PCP can be greatly tested as well,” he said.
Empathy promotes patient adherence to treatment
The new opioid prescription guidelines have increased interest among clinicians in how to improve patient satisfaction with the care for back pain provided, Noel Deep, MD, said in an interview. “These studies address this concern and bring forth an important aspect of the physician-patient relationship, namely the human touch and empathy.”
“I have been a strong proponent of the trust and relationship between a physician and patient; displaying empathy and increased and transparent communication between the physician and the patient has always resulted in better relationships and better outcomes for patients, especially those dealing with chronic health concerns,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.
Potential barriers to effective pain management include beliefs and attitudes on the part of patients, Dr. Deep noted. “Physicians lacking adequate time to communicate effectively with the patient and describe nonopioid and nonsurgical interventions would be another potential barrier.” Other issues include the time and effort, as well as cost, associated with interventions such as physical therapy and other nondrug and nonsurgical interventions. Issues with family and social support and health literacy are also potential barriers to pain management.
Clinical takeaways
Low back pain is one of the most common reasons for a visit in primary care and can be “chronic and debilitating,” Grace Lin, MD, an internal medicine physician and primary care provider at the University of California, San Francisco, said in an interview.
“One issue with the Cochrane Review on exercise is that the studies on exercise were heterogeneous, so it’s difficult to know whether there is a particular kind of exercise that would be most effective and should be recommended to patients,” she said.
Furthermore, she said, “there is a physical therapist shortage in the U.S. I practice in a major city with a large health care system, and it can still take months to get an appointment with a physical therapist.” Also, insurance coverage may limit which therapists a patient can see and how many visits they can have.
“On the clinician side, I think physicians need to be better informed about the evidence base for back pain treatment, namely that exercise is effective and that, long term, analgesics are not,” Dr. Lin said. “This might decrease overprescription of ineffective analgesics and encourage more education about and referrals to physical therapy.”
“Physicians should continue to educate patients that physical therapy is the first-line treatment for back pain and that pain medications are secondary,” she said. “I think that analgesics can be effective for the short term to get people to a point where they feel well enough to do physical therapy. Duloxetine also appears to be moderately effective for chronic low back pain, in part because it may also help address coexisting depression and anxiety,” but these options should be reserved for adjuncts to physical therapy for back pain.
The findings from the study on empathy and communication suggest that the main challenges to these behaviors are systemic, said Dr. Lin.
“Our health care system is not conducive to treating chronic back pain,” she said. Primary care visits that last for 15 or 20 minutes are not long enough to diagnose and counsel patients on such a complex problem as chronic low back pain. Since back pain is usually not the only issue the primary care physician is dealing with during that visit, this can lead to patients feeling like their doctor isn’t listening to them and doesn’t care about their pain.
“We need to better understand the mechanisms by which people develop chronic, debilitating back pain,” Dr. Lin said. “I think if we understood this better, more effective and targeted treatments, both pharmacological and nonpharmacological, could be developed.”
The Annals of Family Medicine study received no outside funding, and the researchers had no financial conflicts to disclose. The Cochrane Reviews was supported by the National Institute for Health and Care Research’s Health Technology Assessment program, and the authors had no financial conflicts to disclose. Dr. Golden and Dr. Deep had no financial conflicts to disclose and serve on the editorial advisory board of Internal Medicine News. Dr. Lin disclosed receiving research funding from the Institute for Clinical and Economic Review and the National Institutes of Health.
Metformin linked to reduced osteoarthritis risk
Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.
“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.
The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.
In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.
The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.
Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.
The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).
“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.
This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.
”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.
Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.
Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.
Nonsignificant lower risk for posttraumatic knee osteoarthritis
Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.
Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.
Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.
Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).
In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.
“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.
The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.
Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.
“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.
The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.
In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.
The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.
Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.
The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).
“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.
This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.
”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.
Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.
Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.
Nonsignificant lower risk for posttraumatic knee osteoarthritis
Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.
Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.
Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.
Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).
In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.
“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.
The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.
Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.
“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.
The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.
In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.
The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.
Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.
The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).
“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.
This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.
”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.
Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.
Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.
Nonsignificant lower risk for posttraumatic knee osteoarthritis
Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.
Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.
Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.
Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).
In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.
“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.
The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.
FROM JAMA NETWORK OPEN AND OARSI 2023
Metabolic syndrome linked to knee pain in middle adulthood
DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.
To supplement existing evidence on the association between metabolic syndrome and joint pain in older adults, the researchers investigated the association in middle-aged adults over a 10- to 13-year period.
The researchers analyzed data from the Childhood Determinants of Adult Health study, which enrolled 2,447 adults with an average age of 31 between 2004 and 2006 and conducted follow-up in 1,549 participants with an average age of 44, during 2014-2019. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used at follow-up only to assess knee symptoms of pain, stiffness, and dysfunction, as well as the overall score.
Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:
- Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
- Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
- Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
- Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.
The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.
At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.
Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).
Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.
The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).
Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.
“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”
Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”
Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.
DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.
To supplement existing evidence on the association between metabolic syndrome and joint pain in older adults, the researchers investigated the association in middle-aged adults over a 10- to 13-year period.
The researchers analyzed data from the Childhood Determinants of Adult Health study, which enrolled 2,447 adults with an average age of 31 between 2004 and 2006 and conducted follow-up in 1,549 participants with an average age of 44, during 2014-2019. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used at follow-up only to assess knee symptoms of pain, stiffness, and dysfunction, as well as the overall score.
Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:
- Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
- Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
- Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
- Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.
The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.
At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.
Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).
Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.
The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).
Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.
“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”
Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”
Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.
DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.
To supplement existing evidence on the association between metabolic syndrome and joint pain in older adults, the researchers investigated the association in middle-aged adults over a 10- to 13-year period.
The researchers analyzed data from the Childhood Determinants of Adult Health study, which enrolled 2,447 adults with an average age of 31 between 2004 and 2006 and conducted follow-up in 1,549 participants with an average age of 44, during 2014-2019. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used at follow-up only to assess knee symptoms of pain, stiffness, and dysfunction, as well as the overall score.
Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:
- Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
- Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
- Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
- Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.
The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.
At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.
Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).
Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.
The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).
Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.
“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”
Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”
Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.
AT OARSI 2023