EULAR (European League Against Rheumatism): 2015 Congress

ROME – There was no advantage to individually prescribed exercises for knee osteoarthritis over usual physiotherapy in a multicenter, longitudinal, randomized study reported at the European Congress of Rheumatology.

Indeed, the results of the United Kingdom–based Benefits of Effective Exercise for knee Pain (BEEP) study showed that all of three of the interventions tested improved patients’ pain and physical function to a similar degree over the 18-month follow-up period.

“Clearer identification of those who respond to exercise, rather than changing the characteristics of exercise programs, is needed in future research,” suggested the presenting author Emma Healey, Ph.D., of Keele University, Staffordshire, England.

The aim of the BEEP was to see if changing the characteristics of exercise programs could improve patients’ outcomes when compared with usual physiotherapy. A total of 65 general practices, five National Health Service physiotherapy services, and 47 physiotherapists took part in the study and recruited 526 adults aged 45 years or older with knee osteoarthritis (OA) from a total of 1,530 who had been screened.

Three different interventions were compared: usual physiotherapy care consisting of up to four treatment sessions over 12 weeks (176 patients), an individually tailored and supervised exercise (ITE) program consisting of six to eight sessions over 12 weeks (178 patients), and a targeted exercise adherence (TEA) program consisting of 8-10 sessions over 6 months (172 patients). Data were collected at 3, 6, 9 and 18 months via postal questionnaires.

Participants in all groups received an advice booklet outlining the benefits of exercise and exercises to perform. Exercises were focused on the lower limb and selected from a template in the usual care group but individually prescribed and supervised in the other two groups. Patients in the TEA group also had exercises aimed at improving their overall fitness. An exercise diary was completed by those in the ITE group and an ‘adherence-enhancing toolkit’ was used by the TEA group.

The primary outcome measure used was change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scales at 6 months. On a scale of 0-20, no clinically or statistically significant differences were seen between the groups, with pain scores of 6.4, 6.4, and 6.2 for the usual care, ITE, and TEA groups, respectively. A similar pattern was seen for function scores (21.4, 22.3, 21.5, respectively) assessed on a scale of 0-68. These findings didn’t change over time, with all patients doing well with longer follow-up, Dr. Healey observed.

Clinical effectiveness was also evaluated according to Outcome Measures in Rheumatology–Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria, but again no differences between the groups were found, with around half of the study population fitting responder criteria at 6 months.

Although patients’ self-reported adherence to their exercise was high at the 3-month assessment (75%-77%), it gradually declined over the course of the follow-up period. “Exercise behavior was back to baseline levels by 18 months,” Dr. Healey noted. Self-reported adherence appeared to remain higher for longer in the TEA group, but differences between treatment groups were again not statistically significant upon closer evaluation.

Usual physiotherapy had an edge over the other interventions in terms of both effectiveness measured in quality-adjusted life-years and knee OA–related resource use at 18 months’ follow-up, according to an economic evaluation.

“Economic analysis suggests usual care is ‘treatment of choice,’ ” Dr. Healey said.

The research was funded by the National Institute for Health Research and Arthritis UK. Dr. Healey reported having no financial disclosures.

ROME – There was no advantage to individually prescribed exercises for knee osteoarthritis over usual physiotherapy in a multicenter, longitudinal, randomized study reported at the European Congress of Rheumatology.

Indeed, the results of the United Kingdom–based Benefits of Effective Exercise for knee Pain (BEEP) study showed that all of three of the interventions tested improved patients’ pain and physical function to a similar degree over the 18-month follow-up period.

“Clearer identification of those who respond to exercise, rather than changing the characteristics of exercise programs, is needed in future research,” suggested the presenting author Emma Healey, Ph.D., of Keele University, Staffordshire, England.

The aim of the BEEP was to see if changing the characteristics of exercise programs could improve patients’ outcomes when compared with usual physiotherapy. A total of 65 general practices, five National Health Service physiotherapy services, and 47 physiotherapists took part in the study and recruited 526 adults aged 45 years or older with knee osteoarthritis (OA) from a total of 1,530 who had been screened.

Three different interventions were compared: usual physiotherapy care consisting of up to four treatment sessions over 12 weeks (176 patients), an individually tailored and supervised exercise (ITE) program consisting of six to eight sessions over 12 weeks (178 patients), and a targeted exercise adherence (TEA) program consisting of 8-10 sessions over 6 months (172 patients). Data were collected at 3, 6, 9 and 18 months via postal questionnaires.

Participants in all groups received an advice booklet outlining the benefits of exercise and exercises to perform. Exercises were focused on the lower limb and selected from a template in the usual care group but individually prescribed and supervised in the other two groups. Patients in the TEA group also had exercises aimed at improving their overall fitness. An exercise diary was completed by those in the ITE group and an ‘adherence-enhancing toolkit’ was used by the TEA group.

The primary outcome measure used was change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scales at 6 months. On a scale of 0-20, no clinically or statistically significant differences were seen between the groups, with pain scores of 6.4, 6.4, and 6.2 for the usual care, ITE, and TEA groups, respectively. A similar pattern was seen for function scores (21.4, 22.3, 21.5, respectively) assessed on a scale of 0-68. These findings didn’t change over time, with all patients doing well with longer follow-up, Dr. Healey observed.

Clinical effectiveness was also evaluated according to Outcome Measures in Rheumatology–Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria, but again no differences between the groups were found, with around half of the study population fitting responder criteria at 6 months.

Although patients’ self-reported adherence to their exercise was high at the 3-month assessment (75%-77%), it gradually declined over the course of the follow-up period. “Exercise behavior was back to baseline levels by 18 months,” Dr. Healey noted. Self-reported adherence appeared to remain higher for longer in the TEA group, but differences between treatment groups were again not statistically significant upon closer evaluation.

Usual physiotherapy had an edge over the other interventions in terms of both effectiveness measured in quality-adjusted life-years and knee OA–related resource use at 18 months’ follow-up, according to an economic evaluation.

“Economic analysis suggests usual care is ‘treatment of choice,’ ” Dr. Healey said.

The research was funded by the National Institute for Health Research and Arthritis UK. Dr. Healey reported having no financial disclosures.

ROME – There was no advantage to individually prescribed exercises for knee osteoarthritis over usual physiotherapy in a multicenter, longitudinal, randomized study reported at the European Congress of Rheumatology.

Indeed, the results of the United Kingdom–based Benefits of Effective Exercise for knee Pain (BEEP) study showed that all of three of the interventions tested improved patients’ pain and physical function to a similar degree over the 18-month follow-up period.

“Clearer identification of those who respond to exercise, rather than changing the characteristics of exercise programs, is needed in future research,” suggested the presenting author Emma Healey, Ph.D., of Keele University, Staffordshire, England.

The aim of the BEEP was to see if changing the characteristics of exercise programs could improve patients’ outcomes when compared with usual physiotherapy. A total of 65 general practices, five National Health Service physiotherapy services, and 47 physiotherapists took part in the study and recruited 526 adults aged 45 years or older with knee osteoarthritis (OA) from a total of 1,530 who had been screened.

Three different interventions were compared: usual physiotherapy care consisting of up to four treatment sessions over 12 weeks (176 patients), an individually tailored and supervised exercise (ITE) program consisting of six to eight sessions over 12 weeks (178 patients), and a targeted exercise adherence (TEA) program consisting of 8-10 sessions over 6 months (172 patients). Data were collected at 3, 6, 9 and 18 months via postal questionnaires.

Participants in all groups received an advice booklet outlining the benefits of exercise and exercises to perform. Exercises were focused on the lower limb and selected from a template in the usual care group but individually prescribed and supervised in the other two groups. Patients in the TEA group also had exercises aimed at improving their overall fitness. An exercise diary was completed by those in the ITE group and an ‘adherence-enhancing toolkit’ was used by the TEA group.

The primary outcome measure used was change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scales at 6 months. On a scale of 0-20, no clinically or statistically significant differences were seen between the groups, with pain scores of 6.4, 6.4, and 6.2 for the usual care, ITE, and TEA groups, respectively. A similar pattern was seen for function scores (21.4, 22.3, 21.5, respectively) assessed on a scale of 0-68. These findings didn’t change over time, with all patients doing well with longer follow-up, Dr. Healey observed.

Clinical effectiveness was also evaluated according to Outcome Measures in Rheumatology–Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria, but again no differences between the groups were found, with around half of the study population fitting responder criteria at 6 months.

Although patients’ self-reported adherence to their exercise was high at the 3-month assessment (75%-77%), it gradually declined over the course of the follow-up period. “Exercise behavior was back to baseline levels by 18 months,” Dr. Healey noted. Self-reported adherence appeared to remain higher for longer in the TEA group, but differences between treatment groups were again not statistically significant upon closer evaluation.

Usual physiotherapy had an edge over the other interventions in terms of both effectiveness measured in quality-adjusted life-years and knee OA–related resource use at 18 months’ follow-up, according to an economic evaluation.

“Economic analysis suggests usual care is ‘treatment of choice,’ ” Dr. Healey said.

The research was funded by the National Institute for Health Research and Arthritis UK. Dr. Healey reported having no financial disclosures.

ROME – Erosive hand osteoarthritis (OA) is probably a more severe form of the disease, rather than a separate clinical entity, a team of Norwegian researchers has suggested.

Dr. Alexander Mathiessen and associates from Diakonhjemmet Hospital in Oslo found that synovial inflammation was more common in patients with erosive disease. However, when they stratified the 293 patients studied according to the degree of structural joint damage, they found that the differences disappeared.

“Modern imaging techniques such as MRI and ultrasound have shown high prevalence of synovitis in hand osteoarthritis,” they explained in a poster presentation at the European Congress of Rheumatology.

Although erosive hand OA is often considered a more inflammatory phenotype, with more pain and disability and a more aggressive disease course, “it has been debated whether erosive hand OA is an inflammatory subset with more synovitis than conventional OA, or just a severe form of the disease” they observed.

Although a recent study (Ann. Rheum. Dis. 2013;72:930-4) had found a higher frequency of inflammation in patients with erosive hand OA versus nonerosive hand OA, the study had not adjusted for the severity of structural damage. Dr. Mathiessen and coworkers therefore set out to examine whether the higher prevalence of synovitis that had been seen in patients with erosive hand OA was linked to the extent of joint disease according to the Kellgren-Lawrence (KL) scale.

The team used data from the Musculoskeletal Pain in Ullensaker Study (MUST) cohort (BMC Musculoskelet. Disord. 2013;14:201), an observational study comprising 630 participants with self-reported OA. Their analysis used data on 293 patients who reported having hand OA and who fulfilled American College of Rheumatology criteria, with no other inflammatory joint disease.

The majority (76%) of patients with hand OA studied were women, with a mean age of 64.9 years. There were over 4,000 joints examined using both ultrasonography and radiography of which 359 (7.9%) were erosive.

“We focused mainly on the proximal and distal interphalangeal joints, since radiographic erosions occur in these joints mainly,” the researchers said.

Just fewer than 30% (n = 86) participants had at least one erosive interphalangeal joint. The median number of these finger joints involved was five, ranging from 0 to 15.

Grey scale (GS) and power Doppler (PD) synovitis was seen in 18.9% and 1.8% of patients with erosive hand OA and 11.1% and 0.4% of those with nonerosive hand OA, respectively (P < .001 for both comparisons).

Patients with erosive disease were more likely to have greater joint damage on the KL scale than patients with nonerosive disease, with 41.7% versus 4.5%, respectively, having a KL grade of 3-4 and 26.7% versus 64% having a KL grade of 0­-1.

The team reported that the prevalence of both GS and PD synovitis increases with more structural joint damage irrespective of erosive status and that there was a similar level of joint inflammation when data were stratified according to KL grade.

Somewhat paradoxically, they said, “erosive joints actually have less inflammation than nonerosive joints.”

The investigators did not report having any disclosures.

ROME – Erosive hand osteoarthritis (OA) is probably a more severe form of the disease, rather than a separate clinical entity, a team of Norwegian researchers has suggested.

Dr. Alexander Mathiessen and associates from Diakonhjemmet Hospital in Oslo found that synovial inflammation was more common in patients with erosive disease. However, when they stratified the 293 patients studied according to the degree of structural joint damage, they found that the differences disappeared.

“Modern imaging techniques such as MRI and ultrasound have shown high prevalence of synovitis in hand osteoarthritis,” they explained in a poster presentation at the European Congress of Rheumatology.

Although erosive hand OA is often considered a more inflammatory phenotype, with more pain and disability and a more aggressive disease course, “it has been debated whether erosive hand OA is an inflammatory subset with more synovitis than conventional OA, or just a severe form of the disease” they observed.

Although a recent study (Ann. Rheum. Dis. 2013;72:930-4) had found a higher frequency of inflammation in patients with erosive hand OA versus nonerosive hand OA, the study had not adjusted for the severity of structural damage. Dr. Mathiessen and coworkers therefore set out to examine whether the higher prevalence of synovitis that had been seen in patients with erosive hand OA was linked to the extent of joint disease according to the Kellgren-Lawrence (KL) scale.

The team used data from the Musculoskeletal Pain in Ullensaker Study (MUST) cohort (BMC Musculoskelet. Disord. 2013;14:201), an observational study comprising 630 participants with self-reported OA. Their analysis used data on 293 patients who reported having hand OA and who fulfilled American College of Rheumatology criteria, with no other inflammatory joint disease.

The majority (76%) of patients with hand OA studied were women, with a mean age of 64.9 years. There were over 4,000 joints examined using both ultrasonography and radiography of which 359 (7.9%) were erosive.

“We focused mainly on the proximal and distal interphalangeal joints, since radiographic erosions occur in these joints mainly,” the researchers said.

Just fewer than 30% (n = 86) participants had at least one erosive interphalangeal joint. The median number of these finger joints involved was five, ranging from 0 to 15.

Grey scale (GS) and power Doppler (PD) synovitis was seen in 18.9% and 1.8% of patients with erosive hand OA and 11.1% and 0.4% of those with nonerosive hand OA, respectively (P < .001 for both comparisons).

Patients with erosive disease were more likely to have greater joint damage on the KL scale than patients with nonerosive disease, with 41.7% versus 4.5%, respectively, having a KL grade of 3-4 and 26.7% versus 64% having a KL grade of 0­-1.

The team reported that the prevalence of both GS and PD synovitis increases with more structural joint damage irrespective of erosive status and that there was a similar level of joint inflammation when data were stratified according to KL grade.

Somewhat paradoxically, they said, “erosive joints actually have less inflammation than nonerosive joints.”

The investigators did not report having any disclosures.

ROME – Erosive hand osteoarthritis (OA) is probably a more severe form of the disease, rather than a separate clinical entity, a team of Norwegian researchers has suggested.

Dr. Alexander Mathiessen and associates from Diakonhjemmet Hospital in Oslo found that synovial inflammation was more common in patients with erosive disease. However, when they stratified the 293 patients studied according to the degree of structural joint damage, they found that the differences disappeared.

“Modern imaging techniques such as MRI and ultrasound have shown high prevalence of synovitis in hand osteoarthritis,” they explained in a poster presentation at the European Congress of Rheumatology.

Although erosive hand OA is often considered a more inflammatory phenotype, with more pain and disability and a more aggressive disease course, “it has been debated whether erosive hand OA is an inflammatory subset with more synovitis than conventional OA, or just a severe form of the disease” they observed.

Although a recent study (Ann. Rheum. Dis. 2013;72:930-4) had found a higher frequency of inflammation in patients with erosive hand OA versus nonerosive hand OA, the study had not adjusted for the severity of structural damage. Dr. Mathiessen and coworkers therefore set out to examine whether the higher prevalence of synovitis that had been seen in patients with erosive hand OA was linked to the extent of joint disease according to the Kellgren-Lawrence (KL) scale.

The team used data from the Musculoskeletal Pain in Ullensaker Study (MUST) cohort (BMC Musculoskelet. Disord. 2013;14:201), an observational study comprising 630 participants with self-reported OA. Their analysis used data on 293 patients who reported having hand OA and who fulfilled American College of Rheumatology criteria, with no other inflammatory joint disease.

The majority (76%) of patients with hand OA studied were women, with a mean age of 64.9 years. There were over 4,000 joints examined using both ultrasonography and radiography of which 359 (7.9%) were erosive.

“We focused mainly on the proximal and distal interphalangeal joints, since radiographic erosions occur in these joints mainly,” the researchers said.

Just fewer than 30% (n = 86) participants had at least one erosive interphalangeal joint. The median number of these finger joints involved was five, ranging from 0 to 15.

Grey scale (GS) and power Doppler (PD) synovitis was seen in 18.9% and 1.8% of patients with erosive hand OA and 11.1% and 0.4% of those with nonerosive hand OA, respectively (P < .001 for both comparisons).

Patients with erosive disease were more likely to have greater joint damage on the KL scale than patients with nonerosive disease, with 41.7% versus 4.5%, respectively, having a KL grade of 3-4 and 26.7% versus 64% having a KL grade of 0­-1.

The team reported that the prevalence of both GS and PD synovitis increases with more structural joint damage irrespective of erosive status and that there was a similar level of joint inflammation when data were stratified according to KL grade.

Somewhat paradoxically, they said, “erosive joints actually have less inflammation than nonerosive joints.”

The investigators did not report having any disclosures.

ROME – Combined intra-articular injections of Tr14 (Traumeel) and Ze14 (Zeel) provided statistically significant, clinically relevant, and long-lasting relief of knee osteoarthritis pain in a phase III, randomized, double-blind, placebo-controlled trial.

The size of the effect was consistent with that seen for other pain-relieving drugs used to manage knee osteoarthritis (OA), including intra-articular (IA) injections of hyaluronic acid and corticosteroids, and even oral administration of diclofenac, the study investigators reported.

“From a qualitative perspective, the risk-benefit relationship for Tr14&Ze14 appears favorable, particularly compared to oral NSAIDs,” noted Dr. Carlos Lozada and his associates in a poster presentation at the European Congress of Rheumatology.

Dr. Lozada of the University of Miami noted in an interview that, unlike oral NSAIDs, the safety profile of Tr14&Ze14 was “benign, with no signals of cardiovascular, gastrointestinal, or other concerning risks,” which might offer an advantage for patients who are unable to take NSAIDs but still need something to provide OA pain relief.

According to their individual prescribing information, Tr14 and Ze14 are two homeopathic medicines available for the management of various musculoskeletal disorders and, in combination, for inflammatory and degenerative conditions such as OA. They each contain 14 different components, such as arnica, belladonna, echinacea, and comfrey root, and can be given by subcutaneous, intradermal, intramuscular, IA, or intravenous administration.

The MOZART (Study of Intra-articular Injections vs. Placebo in Patients With Pain From Osteoarthritis of the Knee) trial was conducted at 30 clinical study sites in the United States and involved 232 patients with moderate to severe pain associated with knee OA. Patients were randomized to weekly IA injections of Tr14&Ze14 for 3 weeks or to intra-articular placebo injections.

The main results were presented at the annual meeting of the American College of Rheumatology in Boston last year (Arthritis Rheumatol. 2014;66:S1266[Abstr. 2896]) and showed that significantly improved knee OA pain – assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale – was achieved after 8 days with Tr14&Ze14 vs. IA placebo injections.

The current analysis looked at the size of the effect achieved using the Hedges’ g* statistical method, which is a calculation based on the difference between treatment means, divided by the estimated common standard deviation, and then multiplied by a correlation factor that adjusts for sample sizes. Comparing the size of the effect seen with Tr14&Ze14 vs. IA placebo injections for the WOMAC pain subscale over time showed a consistent pain-relieving benefit of 0.26 at 15 days’ assessment, 0.22 at 29 days, 0.30 at 43 days, 0.31 at 57 days, 0.30 at 71 days, 0.25 at 85 days, and 0.25 at 99 days, the final assessment point in the study.

These effect sizes were then compared with those seen with other treatments used for OA pain relief obtained from a recent meta-analysis of 129 trials (Ann. Intern. Med. 2015;162:46–54). In that meta-analysis, IA administration of anti-inflammatory medicines was found to be superior to oral NSAIDs for the relief of pain. While this may partly do due to an integrated placebo effect of having injections, small but robust differences were seen between the active treatments, the meta-analysis’ authors concluded.

Using IA placebo injections as the comparator, the meta-analysis found that the Hedges’ g* effect sizes at 3 months were 0.34 for IA injections of hyaluronic acid and 0.32 for IA injections of corticosteroids. Effect sizes for commonly used oral NSAIDs were 0.23 for diclofenac, 0.15 for ibuprofen, 0.09 for naproxen, and 0.04 for celecoxib.

Dr. Lozada noted that while the current trial data showed that a consistent and long-lasting pain-relieving effect could be achieved following just three weekly IA injections of Tr14&Ze14, they cannot provide information on when to re-treat patients.

“One reason the follow up was for 99 days was to try to get some notion of how long the effect would last,” he said. “It doesn’t answer the question at this point on when you have to re-treat, I think that will still have to be individualized according to the patient.”

The study was sponsored by Biologische Heilmittel Heel GmbH. Dr. Lozada is a consultant for Rio Pharmaceutical Services and Heel Inc.

ROME – Combined intra-articular injections of Tr14 (Traumeel) and Ze14 (Zeel) provided statistically significant, clinically relevant, and long-lasting relief of knee osteoarthritis pain in a phase III, randomized, double-blind, placebo-controlled trial.

The size of the effect was consistent with that seen for other pain-relieving drugs used to manage knee osteoarthritis (OA), including intra-articular (IA) injections of hyaluronic acid and corticosteroids, and even oral administration of diclofenac, the study investigators reported.

“From a qualitative perspective, the risk-benefit relationship for Tr14&Ze14 appears favorable, particularly compared to oral NSAIDs,” noted Dr. Carlos Lozada and his associates in a poster presentation at the European Congress of Rheumatology.

Dr. Lozada of the University of Miami noted in an interview that, unlike oral NSAIDs, the safety profile of Tr14&Ze14 was “benign, with no signals of cardiovascular, gastrointestinal, or other concerning risks,” which might offer an advantage for patients who are unable to take NSAIDs but still need something to provide OA pain relief.

According to their individual prescribing information, Tr14 and Ze14 are two homeopathic medicines available for the management of various musculoskeletal disorders and, in combination, for inflammatory and degenerative conditions such as OA. They each contain 14 different components, such as arnica, belladonna, echinacea, and comfrey root, and can be given by subcutaneous, intradermal, intramuscular, IA, or intravenous administration.

The MOZART (Study of Intra-articular Injections vs. Placebo in Patients With Pain From Osteoarthritis of the Knee) trial was conducted at 30 clinical study sites in the United States and involved 232 patients with moderate to severe pain associated with knee OA. Patients were randomized to weekly IA injections of Tr14&Ze14 for 3 weeks or to intra-articular placebo injections.

The main results were presented at the annual meeting of the American College of Rheumatology in Boston last year (Arthritis Rheumatol. 2014;66:S1266[Abstr. 2896]) and showed that significantly improved knee OA pain – assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale – was achieved after 8 days with Tr14&Ze14 vs. IA placebo injections.

The current analysis looked at the size of the effect achieved using the Hedges’ g* statistical method, which is a calculation based on the difference between treatment means, divided by the estimated common standard deviation, and then multiplied by a correlation factor that adjusts for sample sizes. Comparing the size of the effect seen with Tr14&Ze14 vs. IA placebo injections for the WOMAC pain subscale over time showed a consistent pain-relieving benefit of 0.26 at 15 days’ assessment, 0.22 at 29 days, 0.30 at 43 days, 0.31 at 57 days, 0.30 at 71 days, 0.25 at 85 days, and 0.25 at 99 days, the final assessment point in the study.

These effect sizes were then compared with those seen with other treatments used for OA pain relief obtained from a recent meta-analysis of 129 trials (Ann. Intern. Med. 2015;162:46–54). In that meta-analysis, IA administration of anti-inflammatory medicines was found to be superior to oral NSAIDs for the relief of pain. While this may partly do due to an integrated placebo effect of having injections, small but robust differences were seen between the active treatments, the meta-analysis’ authors concluded.

Using IA placebo injections as the comparator, the meta-analysis found that the Hedges’ g* effect sizes at 3 months were 0.34 for IA injections of hyaluronic acid and 0.32 for IA injections of corticosteroids. Effect sizes for commonly used oral NSAIDs were 0.23 for diclofenac, 0.15 for ibuprofen, 0.09 for naproxen, and 0.04 for celecoxib.

Dr. Lozada noted that while the current trial data showed that a consistent and long-lasting pain-relieving effect could be achieved following just three weekly IA injections of Tr14&Ze14, they cannot provide information on when to re-treat patients.

“One reason the follow up was for 99 days was to try to get some notion of how long the effect would last,” he said. “It doesn’t answer the question at this point on when you have to re-treat, I think that will still have to be individualized according to the patient.”

The study was sponsored by Biologische Heilmittel Heel GmbH. Dr. Lozada is a consultant for Rio Pharmaceutical Services and Heel Inc.

ROME – Combined intra-articular injections of Tr14 (Traumeel) and Ze14 (Zeel) provided statistically significant, clinically relevant, and long-lasting relief of knee osteoarthritis pain in a phase III, randomized, double-blind, placebo-controlled trial.

The size of the effect was consistent with that seen for other pain-relieving drugs used to manage knee osteoarthritis (OA), including intra-articular (IA) injections of hyaluronic acid and corticosteroids, and even oral administration of diclofenac, the study investigators reported.

“From a qualitative perspective, the risk-benefit relationship for Tr14&Ze14 appears favorable, particularly compared to oral NSAIDs,” noted Dr. Carlos Lozada and his associates in a poster presentation at the European Congress of Rheumatology.

Dr. Lozada of the University of Miami noted in an interview that, unlike oral NSAIDs, the safety profile of Tr14&Ze14 was “benign, with no signals of cardiovascular, gastrointestinal, or other concerning risks,” which might offer an advantage for patients who are unable to take NSAIDs but still need something to provide OA pain relief.

According to their individual prescribing information, Tr14 and Ze14 are two homeopathic medicines available for the management of various musculoskeletal disorders and, in combination, for inflammatory and degenerative conditions such as OA. They each contain 14 different components, such as arnica, belladonna, echinacea, and comfrey root, and can be given by subcutaneous, intradermal, intramuscular, IA, or intravenous administration.

The MOZART (Study of Intra-articular Injections vs. Placebo in Patients With Pain From Osteoarthritis of the Knee) trial was conducted at 30 clinical study sites in the United States and involved 232 patients with moderate to severe pain associated with knee OA. Patients were randomized to weekly IA injections of Tr14&Ze14 for 3 weeks or to intra-articular placebo injections.

The main results were presented at the annual meeting of the American College of Rheumatology in Boston last year (Arthritis Rheumatol. 2014;66:S1266[Abstr. 2896]) and showed that significantly improved knee OA pain – assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale – was achieved after 8 days with Tr14&Ze14 vs. IA placebo injections.

The current analysis looked at the size of the effect achieved using the Hedges’ g* statistical method, which is a calculation based on the difference between treatment means, divided by the estimated common standard deviation, and then multiplied by a correlation factor that adjusts for sample sizes. Comparing the size of the effect seen with Tr14&Ze14 vs. IA placebo injections for the WOMAC pain subscale over time showed a consistent pain-relieving benefit of 0.26 at 15 days’ assessment, 0.22 at 29 days, 0.30 at 43 days, 0.31 at 57 days, 0.30 at 71 days, 0.25 at 85 days, and 0.25 at 99 days, the final assessment point in the study.

These effect sizes were then compared with those seen with other treatments used for OA pain relief obtained from a recent meta-analysis of 129 trials (Ann. Intern. Med. 2015;162:46–54). In that meta-analysis, IA administration of anti-inflammatory medicines was found to be superior to oral NSAIDs for the relief of pain. While this may partly do due to an integrated placebo effect of having injections, small but robust differences were seen between the active treatments, the meta-analysis’ authors concluded.

Using IA placebo injections as the comparator, the meta-analysis found that the Hedges’ g* effect sizes at 3 months were 0.34 for IA injections of hyaluronic acid and 0.32 for IA injections of corticosteroids. Effect sizes for commonly used oral NSAIDs were 0.23 for diclofenac, 0.15 for ibuprofen, 0.09 for naproxen, and 0.04 for celecoxib.

Dr. Lozada noted that while the current trial data showed that a consistent and long-lasting pain-relieving effect could be achieved following just three weekly IA injections of Tr14&Ze14, they cannot provide information on when to re-treat patients.

“One reason the follow up was for 99 days was to try to get some notion of how long the effect would last,” he said. “It doesn’t answer the question at this point on when you have to re-treat, I think that will still have to be individualized according to the patient.”

The study was sponsored by Biologische Heilmittel Heel GmbH. Dr. Lozada is a consultant for Rio Pharmaceutical Services and Heel Inc.

ROME – Ensuring that intra-articular injections are correctly placed does not appear to result in better pain management for knee osteoarthritis, according to research presented at the European Congress of Rheumatology.

“Accurate injection neither resulted in higher rate of response to treatment than inaccurate injection nor greater mean pain reduction,” said George Hirsch, Ph.D., of the Institute of Inflammation and Repair at the University of Manchester (England) and the Dudley Group NHS Foundation Trust.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Dr. Hirsch and his associates defined response to treatment as at least a 40% reduction in pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the percentages who met that definition were similar among patients who had their injections correctly placed and those who did not at 3 weeks (57.7% vs. 63.4%, respectively; P = .0355) and 9 weeks (39.3% vs. 51.4%; P = .0148).

There also were no differences between mean pain reduction at 3 weeks (–110.7 mm vs. –116.9 mm on a visual analogue scale; P = .781) and 9 weeks (–65.2 mm vs. –92.8 mm; P = .247) between the patients with accurate and inaccurate intra-articular injection placement.

The researchers aimed to determine if injecting accurately into the knee could have an effect on patients’ pain outcomes because, despite the effectiveness of intra-articular corticosteroid injections (IACIs) for pain in knee OA, “responses to treatment vary.” In the poster presentation, Dr. Hirsch noted that uncertainty remained as to whether structural factors including accurate intra-articular placement mattered in regards to pain reduction.

The practical, prospective, observational study included 141 men and women with a mean age of 63.8 years who had been referred for IACI for their knee OA in a routine practice setting.

Before aspiration and injection into the affected knee(s) based on clinical examination, patients underwent careful x-ray and ultrasound assessment. Following injection, an air arthrosonogram was used to see if injections had entered the joint cavity.

Overall, just over half (53%) of patients were classed as responders at 3 weeks and 44% at 9 weeks, and a positive arthrosonogram was seen in 98 (70%).

In addition to no advantage for accurate injection placement on pain outcomes, there was no indication that individual physical factors mattered either. Mean measurements of sonographic effusion and synovial hypertrophy did not differ between responders and nonresponders at either time point assessed.

Similar findings also were seen for mean scores for power Doppler signal and individual radiographic features of osteoarthritis that included joint-space narrowing and presence of bone spurs.

“These results raise potential questions about the routine use of [ultrasound] to enhance or predict response to IACI in knee OA,” Dr. Hirsch said.

The authors reported having no financial disclosures.

ROME – Ensuring that intra-articular injections are correctly placed does not appear to result in better pain management for knee osteoarthritis, according to research presented at the European Congress of Rheumatology.

“Accurate injection neither resulted in higher rate of response to treatment than inaccurate injection nor greater mean pain reduction,” said George Hirsch, Ph.D., of the Institute of Inflammation and Repair at the University of Manchester (England) and the Dudley Group NHS Foundation Trust.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Dr. Hirsch and his associates defined response to treatment as at least a 40% reduction in pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the percentages who met that definition were similar among patients who had their injections correctly placed and those who did not at 3 weeks (57.7% vs. 63.4%, respectively; P = .0355) and 9 weeks (39.3% vs. 51.4%; P = .0148).

There also were no differences between mean pain reduction at 3 weeks (–110.7 mm vs. –116.9 mm on a visual analogue scale; P = .781) and 9 weeks (–65.2 mm vs. –92.8 mm; P = .247) between the patients with accurate and inaccurate intra-articular injection placement.

The researchers aimed to determine if injecting accurately into the knee could have an effect on patients’ pain outcomes because, despite the effectiveness of intra-articular corticosteroid injections (IACIs) for pain in knee OA, “responses to treatment vary.” In the poster presentation, Dr. Hirsch noted that uncertainty remained as to whether structural factors including accurate intra-articular placement mattered in regards to pain reduction.

The practical, prospective, observational study included 141 men and women with a mean age of 63.8 years who had been referred for IACI for their knee OA in a routine practice setting.

Before aspiration and injection into the affected knee(s) based on clinical examination, patients underwent careful x-ray and ultrasound assessment. Following injection, an air arthrosonogram was used to see if injections had entered the joint cavity.

Overall, just over half (53%) of patients were classed as responders at 3 weeks and 44% at 9 weeks, and a positive arthrosonogram was seen in 98 (70%).

In addition to no advantage for accurate injection placement on pain outcomes, there was no indication that individual physical factors mattered either. Mean measurements of sonographic effusion and synovial hypertrophy did not differ between responders and nonresponders at either time point assessed.

Similar findings also were seen for mean scores for power Doppler signal and individual radiographic features of osteoarthritis that included joint-space narrowing and presence of bone spurs.

“These results raise potential questions about the routine use of [ultrasound] to enhance or predict response to IACI in knee OA,” Dr. Hirsch said.

The authors reported having no financial disclosures.

ROME – Ensuring that intra-articular injections are correctly placed does not appear to result in better pain management for knee osteoarthritis, according to research presented at the European Congress of Rheumatology.

“Accurate injection neither resulted in higher rate of response to treatment than inaccurate injection nor greater mean pain reduction,” said George Hirsch, Ph.D., of the Institute of Inflammation and Repair at the University of Manchester (England) and the Dudley Group NHS Foundation Trust.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Dr. Hirsch and his associates defined response to treatment as at least a 40% reduction in pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the percentages who met that definition were similar among patients who had their injections correctly placed and those who did not at 3 weeks (57.7% vs. 63.4%, respectively; P = .0355) and 9 weeks (39.3% vs. 51.4%; P = .0148).

There also were no differences between mean pain reduction at 3 weeks (–110.7 mm vs. –116.9 mm on a visual analogue scale; P = .781) and 9 weeks (–65.2 mm vs. –92.8 mm; P = .247) between the patients with accurate and inaccurate intra-articular injection placement.

The researchers aimed to determine if injecting accurately into the knee could have an effect on patients’ pain outcomes because, despite the effectiveness of intra-articular corticosteroid injections (IACIs) for pain in knee OA, “responses to treatment vary.” In the poster presentation, Dr. Hirsch noted that uncertainty remained as to whether structural factors including accurate intra-articular placement mattered in regards to pain reduction.

The practical, prospective, observational study included 141 men and women with a mean age of 63.8 years who had been referred for IACI for their knee OA in a routine practice setting.

Before aspiration and injection into the affected knee(s) based on clinical examination, patients underwent careful x-ray and ultrasound assessment. Following injection, an air arthrosonogram was used to see if injections had entered the joint cavity.

Overall, just over half (53%) of patients were classed as responders at 3 weeks and 44% at 9 weeks, and a positive arthrosonogram was seen in 98 (70%).

In addition to no advantage for accurate injection placement on pain outcomes, there was no indication that individual physical factors mattered either. Mean measurements of sonographic effusion and synovial hypertrophy did not differ between responders and nonresponders at either time point assessed.

Similar findings also were seen for mean scores for power Doppler signal and individual radiographic features of osteoarthritis that included joint-space narrowing and presence of bone spurs.

“These results raise potential questions about the routine use of [ultrasound] to enhance or predict response to IACI in knee OA,” Dr. Hirsch said.

The authors reported having no financial disclosures.

ROME – Baricitinib, a novel biologic drug that selectively inhibits certain janus kinases, showed safety and efficacy for treatment of rheumatoid arthritis in a two separate, multicenter, phase III trials that together involved more than 1,200 adult patients.

One study showed baricitinib’s efficacy for rheumatoid arthritis (RA), compared with placebo, in patients previously treated unsuccessfully with at least one tumor necrosis factor (TNF) inhibitor, while the second trial showed similar outcomes in RA patients never before treated with a TNF inhibitor or with any other biologic drug.

Mitchel L. Zoler/Frontline Medical News

“The safety looks acceptable, and the ACR [American College of Rheumatology] 20, 50, and 70 responses look like it will be effective. It looks like a very promising drug that will be another addition to our armamentarium,” Dr. João Fonseca, professor of rheumatology at the University of Lisbon, said at the European Congress of Rheumatology.

But the data so far did not seem to distinguish baricitinib from a similar Janus kinase inhibitor already on the market in Europe and the United States, tofacitinib (Xeljanz), said Dr. Roy Fleischmann, a Dallas-based rheumatologist. “I’m not sure baricitinib is different from tofacitinib in terms of its clinical effect,” he said in an interview, though he hedged that so far results have been reported from just two of the four phase III trials run to date using baricitinib.

Results in patients with prior TNF inhibitor experience

One of the trials, RA-BEACON, enrolled 527 patients with moderate or severe RA at 103 sites in 21 countries including the United States. Patients had to have been treated with at least one TNF inhibitor and could also have been previously treated with other biologic disease-modifying antirheumatic drugs (DMARDs) with either an inadequate response or intolerance to the treatment. More than half the patients had received treatment with at least two biologic DMARDS, and about a quarter had previously been on at least three. Average age of the enrolled patients was 56 years, about 80% were women, and the average duration of RA was 14 years.

The researchers randomized a third of enrolled patients to receive 2 mg of oral baricitinib once daily, a third received 4 mg baricitinib once daily, and a third received placebo. The study’s primary end point was the percentage of patients who achieved an ACR20 response after 12 weeks of treatment, but patients remained on treatment for 24 weeks.

Mitchel L. Zoler/Frontline Medical News

The primary endpoint occurred in 27% of patients on placebo, 49% of those on the 2-mg dose, and 55% of those on the 4-mg dose, statistically significant differences between placebo and each of the active-treatment arms, said Dr. Mark C. Genovese, professor of immunology and rheumatology at Stanford (Calif.) University. Increased ACR20 responses associated with baricitinib treatment first became discernible, compared with placebo, after 1 week on treatment, and after 4 weeks of treatment the impact of baricitinib treatment began to plateau, Dr. Genovese reported.

A notable secondary endpoint was the incidence of remission as measured by the percentage of patients achieving a disease activity score in 28 joints (DAS28) of less than 2.6. When calculated via C-reactive protein levels, remission occurred in 22% of patients after 24 weeks on the 4-mg daily dosage, compared with 6% of placebo patients. DAS28 calculations that used erythrocyte sedimentation rate showed that the rate of remission after 24 weeks among patients on the higher baricitinib dosage reached 9%, compared with a 3% rate among placebo patients.

The safety and tolerability of baricitinib appeared “satisfactory,” Dr. Genovese said. After 24 weeks, patients on the higher dosage had a 10% rate of serious adverse events, compared with a 7% rate in the placebo patients. The overall rate of serious infections was identical in the 4-mg/day group and the placebo patients; herpes zoster occurred in 4% of patients on the higher dosage after 24 weeks, compared with a 1% rate in the placebo group. The rate of grades 1 and 2 neutropenia were also somewhat elevated in patients on the higher dosage after 24 weeks, with a 7% rate of grade 1 neutropenia and a 4% rate of grade 2.

Results in patients without biologic DMARD experience

The RA-BUILD trial had a design very similar to that of RA-BEACON except it exclusively enrolled patients with no prior treatment with any biologic DMARD. The study enrolled 684 patients at 147 centers in 22 countries including the United States. The primary endpoint of the study, the rate of ACR20 responders after 12 weeks on treatment, occurred in 66% of patients randomized to receive 2 mg oral baricitinib daily, 62% of patients receiving 4 mg daily, and 40% of patients on placebo, reported Dr. Maxime Dougados, professor and chief of rheumatology at Cochin Hospital in Paris. The differences between each of the active-treatment groups and the control group were statistically significant.

Mitchel L. Zoler/Frontline Medical News

The rate of patients achieving remission, measured by a clinical disease activity index of 2.8 or less, occurred in 15% of patients who received 2 mg baricitinib daily after 24 weeks as well as in 15% of patients who received the 4-mg dosage after 24 weeks, compared with a 4% rate among the placebo patients, and the comparisons between each of the active-treatment arms and the control group revealed statistically significant differences.

Dr. Dougados also reported data on rates of radiographic progression after 24 weeks, as measured by the van der Heijde modified Sharp score, which showed that treatment with the 4-mg/day dosage of baricitinib resulted in significant reductions in both erosions and joint space narrowing, compared with placebo patients.

Baricitinib treatment in the RA-BUILD study produced a safety profile similar to that seen in the RA-BEACON trial. Dr. Dougados called the safety and tolerability profiles seen in this study “satisfactory.”

RA-BEACON and RA-BUILD were sponsored by Eli Lilly, the company developing baricitinib. Dr. Genovese disclosed ties with Eli Lilly, AbbVie, Astellas, Galapagos, Pfizer, and Vertex. Dr. Dougados has ties with Eli Lilly, AbbVie, Bristol-Myers Squibb, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Fonseca disclosed ties with 12 drug companies. Dr. Fleischmann has ties with many drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Baricitinib, a novel biologic drug that selectively inhibits certain janus kinases, showed safety and efficacy for treatment of rheumatoid arthritis in a two separate, multicenter, phase III trials that together involved more than 1,200 adult patients.

One study showed baricitinib’s efficacy for rheumatoid arthritis (RA), compared with placebo, in patients previously treated unsuccessfully with at least one tumor necrosis factor (TNF) inhibitor, while the second trial showed similar outcomes in RA patients never before treated with a TNF inhibitor or with any other biologic drug.

Mitchel L. Zoler/Frontline Medical News

“The safety looks acceptable, and the ACR [American College of Rheumatology] 20, 50, and 70 responses look like it will be effective. It looks like a very promising drug that will be another addition to our armamentarium,” Dr. João Fonseca, professor of rheumatology at the University of Lisbon, said at the European Congress of Rheumatology.

But the data so far did not seem to distinguish baricitinib from a similar Janus kinase inhibitor already on the market in Europe and the United States, tofacitinib (Xeljanz), said Dr. Roy Fleischmann, a Dallas-based rheumatologist. “I’m not sure baricitinib is different from tofacitinib in terms of its clinical effect,” he said in an interview, though he hedged that so far results have been reported from just two of the four phase III trials run to date using baricitinib.

Results in patients with prior TNF inhibitor experience

One of the trials, RA-BEACON, enrolled 527 patients with moderate or severe RA at 103 sites in 21 countries including the United States. Patients had to have been treated with at least one TNF inhibitor and could also have been previously treated with other biologic disease-modifying antirheumatic drugs (DMARDs) with either an inadequate response or intolerance to the treatment. More than half the patients had received treatment with at least two biologic DMARDS, and about a quarter had previously been on at least three. Average age of the enrolled patients was 56 years, about 80% were women, and the average duration of RA was 14 years.

The researchers randomized a third of enrolled patients to receive 2 mg of oral baricitinib once daily, a third received 4 mg baricitinib once daily, and a third received placebo. The study’s primary end point was the percentage of patients who achieved an ACR20 response after 12 weeks of treatment, but patients remained on treatment for 24 weeks.

Mitchel L. Zoler/Frontline Medical News

The primary endpoint occurred in 27% of patients on placebo, 49% of those on the 2-mg dose, and 55% of those on the 4-mg dose, statistically significant differences between placebo and each of the active-treatment arms, said Dr. Mark C. Genovese, professor of immunology and rheumatology at Stanford (Calif.) University. Increased ACR20 responses associated with baricitinib treatment first became discernible, compared with placebo, after 1 week on treatment, and after 4 weeks of treatment the impact of baricitinib treatment began to plateau, Dr. Genovese reported.

A notable secondary endpoint was the incidence of remission as measured by the percentage of patients achieving a disease activity score in 28 joints (DAS28) of less than 2.6. When calculated via C-reactive protein levels, remission occurred in 22% of patients after 24 weeks on the 4-mg daily dosage, compared with 6% of placebo patients. DAS28 calculations that used erythrocyte sedimentation rate showed that the rate of remission after 24 weeks among patients on the higher baricitinib dosage reached 9%, compared with a 3% rate among placebo patients.

The safety and tolerability of baricitinib appeared “satisfactory,” Dr. Genovese said. After 24 weeks, patients on the higher dosage had a 10% rate of serious adverse events, compared with a 7% rate in the placebo patients. The overall rate of serious infections was identical in the 4-mg/day group and the placebo patients; herpes zoster occurred in 4% of patients on the higher dosage after 24 weeks, compared with a 1% rate in the placebo group. The rate of grades 1 and 2 neutropenia were also somewhat elevated in patients on the higher dosage after 24 weeks, with a 7% rate of grade 1 neutropenia and a 4% rate of grade 2.

Results in patients without biologic DMARD experience

The RA-BUILD trial had a design very similar to that of RA-BEACON except it exclusively enrolled patients with no prior treatment with any biologic DMARD. The study enrolled 684 patients at 147 centers in 22 countries including the United States. The primary endpoint of the study, the rate of ACR20 responders after 12 weeks on treatment, occurred in 66% of patients randomized to receive 2 mg oral baricitinib daily, 62% of patients receiving 4 mg daily, and 40% of patients on placebo, reported Dr. Maxime Dougados, professor and chief of rheumatology at Cochin Hospital in Paris. The differences between each of the active-treatment groups and the control group were statistically significant.

Mitchel L. Zoler/Frontline Medical News

The rate of patients achieving remission, measured by a clinical disease activity index of 2.8 or less, occurred in 15% of patients who received 2 mg baricitinib daily after 24 weeks as well as in 15% of patients who received the 4-mg dosage after 24 weeks, compared with a 4% rate among the placebo patients, and the comparisons between each of the active-treatment arms and the control group revealed statistically significant differences.

Dr. Dougados also reported data on rates of radiographic progression after 24 weeks, as measured by the van der Heijde modified Sharp score, which showed that treatment with the 4-mg/day dosage of baricitinib resulted in significant reductions in both erosions and joint space narrowing, compared with placebo patients.

Baricitinib treatment in the RA-BUILD study produced a safety profile similar to that seen in the RA-BEACON trial. Dr. Dougados called the safety and tolerability profiles seen in this study “satisfactory.”

RA-BEACON and RA-BUILD were sponsored by Eli Lilly, the company developing baricitinib. Dr. Genovese disclosed ties with Eli Lilly, AbbVie, Astellas, Galapagos, Pfizer, and Vertex. Dr. Dougados has ties with Eli Lilly, AbbVie, Bristol-Myers Squibb, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Fonseca disclosed ties with 12 drug companies. Dr. Fleischmann has ties with many drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Baricitinib, a novel biologic drug that selectively inhibits certain janus kinases, showed safety and efficacy for treatment of rheumatoid arthritis in a two separate, multicenter, phase III trials that together involved more than 1,200 adult patients.

One study showed baricitinib’s efficacy for rheumatoid arthritis (RA), compared with placebo, in patients previously treated unsuccessfully with at least one tumor necrosis factor (TNF) inhibitor, while the second trial showed similar outcomes in RA patients never before treated with a TNF inhibitor or with any other biologic drug.

Mitchel L. Zoler/Frontline Medical News

“The safety looks acceptable, and the ACR [American College of Rheumatology] 20, 50, and 70 responses look like it will be effective. It looks like a very promising drug that will be another addition to our armamentarium,” Dr. João Fonseca, professor of rheumatology at the University of Lisbon, said at the European Congress of Rheumatology.

But the data so far did not seem to distinguish baricitinib from a similar Janus kinase inhibitor already on the market in Europe and the United States, tofacitinib (Xeljanz), said Dr. Roy Fleischmann, a Dallas-based rheumatologist. “I’m not sure baricitinib is different from tofacitinib in terms of its clinical effect,” he said in an interview, though he hedged that so far results have been reported from just two of the four phase III trials run to date using baricitinib.

Results in patients with prior TNF inhibitor experience

One of the trials, RA-BEACON, enrolled 527 patients with moderate or severe RA at 103 sites in 21 countries including the United States. Patients had to have been treated with at least one TNF inhibitor and could also have been previously treated with other biologic disease-modifying antirheumatic drugs (DMARDs) with either an inadequate response or intolerance to the treatment. More than half the patients had received treatment with at least two biologic DMARDS, and about a quarter had previously been on at least three. Average age of the enrolled patients was 56 years, about 80% were women, and the average duration of RA was 14 years.

The researchers randomized a third of enrolled patients to receive 2 mg of oral baricitinib once daily, a third received 4 mg baricitinib once daily, and a third received placebo. The study’s primary end point was the percentage of patients who achieved an ACR20 response after 12 weeks of treatment, but patients remained on treatment for 24 weeks.

Mitchel L. Zoler/Frontline Medical News

The primary endpoint occurred in 27% of patients on placebo, 49% of those on the 2-mg dose, and 55% of those on the 4-mg dose, statistically significant differences between placebo and each of the active-treatment arms, said Dr. Mark C. Genovese, professor of immunology and rheumatology at Stanford (Calif.) University. Increased ACR20 responses associated with baricitinib treatment first became discernible, compared with placebo, after 1 week on treatment, and after 4 weeks of treatment the impact of baricitinib treatment began to plateau, Dr. Genovese reported.

A notable secondary endpoint was the incidence of remission as measured by the percentage of patients achieving a disease activity score in 28 joints (DAS28) of less than 2.6. When calculated via C-reactive protein levels, remission occurred in 22% of patients after 24 weeks on the 4-mg daily dosage, compared with 6% of placebo patients. DAS28 calculations that used erythrocyte sedimentation rate showed that the rate of remission after 24 weeks among patients on the higher baricitinib dosage reached 9%, compared with a 3% rate among placebo patients.

The safety and tolerability of baricitinib appeared “satisfactory,” Dr. Genovese said. After 24 weeks, patients on the higher dosage had a 10% rate of serious adverse events, compared with a 7% rate in the placebo patients. The overall rate of serious infections was identical in the 4-mg/day group and the placebo patients; herpes zoster occurred in 4% of patients on the higher dosage after 24 weeks, compared with a 1% rate in the placebo group. The rate of grades 1 and 2 neutropenia were also somewhat elevated in patients on the higher dosage after 24 weeks, with a 7% rate of grade 1 neutropenia and a 4% rate of grade 2.

Results in patients without biologic DMARD experience

The RA-BUILD trial had a design very similar to that of RA-BEACON except it exclusively enrolled patients with no prior treatment with any biologic DMARD. The study enrolled 684 patients at 147 centers in 22 countries including the United States. The primary endpoint of the study, the rate of ACR20 responders after 12 weeks on treatment, occurred in 66% of patients randomized to receive 2 mg oral baricitinib daily, 62% of patients receiving 4 mg daily, and 40% of patients on placebo, reported Dr. Maxime Dougados, professor and chief of rheumatology at Cochin Hospital in Paris. The differences between each of the active-treatment groups and the control group were statistically significant.

Mitchel L. Zoler/Frontline Medical News

The rate of patients achieving remission, measured by a clinical disease activity index of 2.8 or less, occurred in 15% of patients who received 2 mg baricitinib daily after 24 weeks as well as in 15% of patients who received the 4-mg dosage after 24 weeks, compared with a 4% rate among the placebo patients, and the comparisons between each of the active-treatment arms and the control group revealed statistically significant differences.

Dr. Dougados also reported data on rates of radiographic progression after 24 weeks, as measured by the van der Heijde modified Sharp score, which showed that treatment with the 4-mg/day dosage of baricitinib resulted in significant reductions in both erosions and joint space narrowing, compared with placebo patients.

Baricitinib treatment in the RA-BUILD study produced a safety profile similar to that seen in the RA-BEACON trial. Dr. Dougados called the safety and tolerability profiles seen in this study “satisfactory.”

RA-BEACON and RA-BUILD were sponsored by Eli Lilly, the company developing baricitinib. Dr. Genovese disclosed ties with Eli Lilly, AbbVie, Astellas, Galapagos, Pfizer, and Vertex. Dr. Dougados has ties with Eli Lilly, AbbVie, Bristol-Myers Squibb, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Fonseca disclosed ties with 12 drug companies. Dr. Fleischmann has ties with many drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Tai chi is as effective as standard physical therapy in reducing pain and improving physical function and quality of life in patients with knee osteoarthritis, according to the results of a randomized, single-blind study reported at the European Congress of Rheumatology.

The primary outcome of change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score from baseline to 12 weeks was –167.2 mm in the patients randomized to the tai chi group vs. –143.0 mm in those who completed a standard physiotherapy program (P = .16).

©bloodstone/iStockphoto.com

“Future studies of ‘Eastern’ complementary medicine will further inform ‘Western’ medical treatment guidelines,” said Dr. Chenchen Wang, director of the Center for Complementary and Integrative Medicine at Tufts Medical Center in Boston. She noted that the study findings showed that tai chi could be a viable alternative to physical therapy for knee osteoarthritis (OA), which she called “a chronic disabling disease.”

Dr. Wang andher associates have previously shown that the classic Yang-style tai chi results in clinically important improvements in patients with fibromyalgia (N. Engl. J. Med. 2010;363:743-54). They have also previously reported beneficial effects in small numbers of patients with knee OA (Arthritis Rheum. 2009;61:1545–53). The present study findings replicate these results in a larger group of patients followed up for a longer period of time.

“This is the longest follow-up of tai chi for knee osteoarthritis to date,” Dr. Wang observed. It is also representative of a racially diverse population, she said. The study is ongoing but not recruiting participants and will continue to compare the effectiveness and cost-effectiveness of the Chinese martial art vs. standard-of-care physiotherapy for 1 year (BMC Complement. Altern. Med. 2014;14:333).Of 204 randomized patients with a mean age of 60 years and disease duration of 8 years, 167 (82%) completed the tai chi sessions and 12-week evaluation for the primary end point. In addition, three-quarters of patients completed 24 weeks and 69% completed 1 year of the intervention, showing the sustainability of the exercise program. Overall attendance was similar between the groups, at 74% for tai chi and 81% for physical therapy.

The 106 patients randomized to the tai chi group performed the martial art twice a week for 12 weeks while the 98 patients in the physical therapy group underwent twice-weekly sessions for the first 6 weeks, then continued with ”rigorously monitored” exercises at home for 12 additional weeks. Patients knew to which group they had been randomly assigned, but the study physician and outcomes assessments were blinded to the treatment allocation.

Similar benefits were seen for with both strategies for the secondary end points of physical function subscale of the WOMAC (P = .08), Patients’ Global Assessment (P = .06), and chronic pain self-efficacy (P = .22). There were also similar improvements in 6-minute (P = .76) and 20-meter (P = .40) walking tests.

Health-related quality of life measured using the Short Form 36 suggested a possible statistical advantage of tai chi over physical therapy for the physical but not mental component summary, with mean differences between the groups of 3.2 (P < .01) and 1.6 (P = .08), respectively. There was also a statistical difference in depression scores between the groups, but this may not be clinically significant, Dr. Wang observed.

“This study provides evidence to support both tai chi and physical therapy improve pain and physical function for patients with knee osteoarthritis,” she said. “Interestingly, we didn’t see any differences in effectiveness attributable to the four individual tai chi instructors.”

The National Center for Complementary and Integrative Health of the National Institutes of Health supported the study. Dr. Wang reported no relevant conflicts.

ROME – Tai chi is as effective as standard physical therapy in reducing pain and improving physical function and quality of life in patients with knee osteoarthritis, according to the results of a randomized, single-blind study reported at the European Congress of Rheumatology.

The primary outcome of change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score from baseline to 12 weeks was –167.2 mm in the patients randomized to the tai chi group vs. –143.0 mm in those who completed a standard physiotherapy program (P = .16).

©bloodstone/iStockphoto.com

“Future studies of ‘Eastern’ complementary medicine will further inform ‘Western’ medical treatment guidelines,” said Dr. Chenchen Wang, director of the Center for Complementary and Integrative Medicine at Tufts Medical Center in Boston. She noted that the study findings showed that tai chi could be a viable alternative to physical therapy for knee osteoarthritis (OA), which she called “a chronic disabling disease.”

Dr. Wang andher associates have previously shown that the classic Yang-style tai chi results in clinically important improvements in patients with fibromyalgia (N. Engl. J. Med. 2010;363:743-54). They have also previously reported beneficial effects in small numbers of patients with knee OA (Arthritis Rheum. 2009;61:1545–53). The present study findings replicate these results in a larger group of patients followed up for a longer period of time.

“This is the longest follow-up of tai chi for knee osteoarthritis to date,” Dr. Wang observed. It is also representative of a racially diverse population, she said. The study is ongoing but not recruiting participants and will continue to compare the effectiveness and cost-effectiveness of the Chinese martial art vs. standard-of-care physiotherapy for 1 year (BMC Complement. Altern. Med. 2014;14:333).Of 204 randomized patients with a mean age of 60 years and disease duration of 8 years, 167 (82%) completed the tai chi sessions and 12-week evaluation for the primary end point. In addition, three-quarters of patients completed 24 weeks and 69% completed 1 year of the intervention, showing the sustainability of the exercise program. Overall attendance was similar between the groups, at 74% for tai chi and 81% for physical therapy.

The 106 patients randomized to the tai chi group performed the martial art twice a week for 12 weeks while the 98 patients in the physical therapy group underwent twice-weekly sessions for the first 6 weeks, then continued with ”rigorously monitored” exercises at home for 12 additional weeks. Patients knew to which group they had been randomly assigned, but the study physician and outcomes assessments were blinded to the treatment allocation.

Similar benefits were seen for with both strategies for the secondary end points of physical function subscale of the WOMAC (P = .08), Patients’ Global Assessment (P = .06), and chronic pain self-efficacy (P = .22). There were also similar improvements in 6-minute (P = .76) and 20-meter (P = .40) walking tests.

Health-related quality of life measured using the Short Form 36 suggested a possible statistical advantage of tai chi over physical therapy for the physical but not mental component summary, with mean differences between the groups of 3.2 (P < .01) and 1.6 (P = .08), respectively. There was also a statistical difference in depression scores between the groups, but this may not be clinically significant, Dr. Wang observed.

“This study provides evidence to support both tai chi and physical therapy improve pain and physical function for patients with knee osteoarthritis,” she said. “Interestingly, we didn’t see any differences in effectiveness attributable to the four individual tai chi instructors.”

The National Center for Complementary and Integrative Health of the National Institutes of Health supported the study. Dr. Wang reported no relevant conflicts.

ROME – Tai chi is as effective as standard physical therapy in reducing pain and improving physical function and quality of life in patients with knee osteoarthritis, according to the results of a randomized, single-blind study reported at the European Congress of Rheumatology.

The primary outcome of change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score from baseline to 12 weeks was –167.2 mm in the patients randomized to the tai chi group vs. –143.0 mm in those who completed a standard physiotherapy program (P = .16).

©bloodstone/iStockphoto.com

“Future studies of ‘Eastern’ complementary medicine will further inform ‘Western’ medical treatment guidelines,” said Dr. Chenchen Wang, director of the Center for Complementary and Integrative Medicine at Tufts Medical Center in Boston. She noted that the study findings showed that tai chi could be a viable alternative to physical therapy for knee osteoarthritis (OA), which she called “a chronic disabling disease.”

Dr. Wang andher associates have previously shown that the classic Yang-style tai chi results in clinically important improvements in patients with fibromyalgia (N. Engl. J. Med. 2010;363:743-54). They have also previously reported beneficial effects in small numbers of patients with knee OA (Arthritis Rheum. 2009;61:1545–53). The present study findings replicate these results in a larger group of patients followed up for a longer period of time.

“This is the longest follow-up of tai chi for knee osteoarthritis to date,” Dr. Wang observed. It is also representative of a racially diverse population, she said. The study is ongoing but not recruiting participants and will continue to compare the effectiveness and cost-effectiveness of the Chinese martial art vs. standard-of-care physiotherapy for 1 year (BMC Complement. Altern. Med. 2014;14:333).Of 204 randomized patients with a mean age of 60 years and disease duration of 8 years, 167 (82%) completed the tai chi sessions and 12-week evaluation for the primary end point. In addition, three-quarters of patients completed 24 weeks and 69% completed 1 year of the intervention, showing the sustainability of the exercise program. Overall attendance was similar between the groups, at 74% for tai chi and 81% for physical therapy.

The 106 patients randomized to the tai chi group performed the martial art twice a week for 12 weeks while the 98 patients in the physical therapy group underwent twice-weekly sessions for the first 6 weeks, then continued with ”rigorously monitored” exercises at home for 12 additional weeks. Patients knew to which group they had been randomly assigned, but the study physician and outcomes assessments were blinded to the treatment allocation.

Similar benefits were seen for with both strategies for the secondary end points of physical function subscale of the WOMAC (P = .08), Patients’ Global Assessment (P = .06), and chronic pain self-efficacy (P = .22). There were also similar improvements in 6-minute (P = .76) and 20-meter (P = .40) walking tests.

Health-related quality of life measured using the Short Form 36 suggested a possible statistical advantage of tai chi over physical therapy for the physical but not mental component summary, with mean differences between the groups of 3.2 (P < .01) and 1.6 (P = .08), respectively. There was also a statistical difference in depression scores between the groups, but this may not be clinically significant, Dr. Wang observed.

“This study provides evidence to support both tai chi and physical therapy improve pain and physical function for patients with knee osteoarthritis,” she said. “Interestingly, we didn’t see any differences in effectiveness attributable to the four individual tai chi instructors.”

The National Center for Complementary and Integrative Health of the National Institutes of Health supported the study. Dr. Wang reported no relevant conflicts.

ROME – Vitamin D supplementation did not ease osteoarthritic knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index in a 2-year, randomized, double-blind, placebo-controlled trial.

Results of the VIDEO (Vitamin D Effect on Osteoarthritis) study in patients with symptomatic knee osteoarthritis (OA) and low vitamin D levels also showed that replenishing vitamin D also had no effect on the loss of cartilage volume, although there might be a marginal benefit on bone marrow lesions (BMLs) and pain assessed using a visual analog scale (VAS).

“Vitamin D at 50,000 IU/month over 2 years did not meet the primary endpoint in this randomized, controlled trial,” said Jason Jin, a Ph.D. candidate at the Menzies Research Institute, University of Tasmania in Hobart, Australia, who presented the VIDEO study findings at the European Congress of Rheumatology.

He cited a recent commentary published in the Journal of the American Medical Association (JAMA 2015;313:1311-12) that looked at vitamin D research and clinical practice in which the authors said that “clinical enthusiasm for supplemental vitamin D has outpaced available evidence.” This seems to be true considering the results of this and other previous randomized trials, Mr. Jin observed.

“The background of this study is that, in the last decade, vitamin D has become a hot topic in osteoarthritis research and epidemiologic studies have found that vitamin D deficiency is very common in knee osteoarthritis patients,” he said. Low levels of vitamin D have been linked to increased knee pain, radiographic progression, and increased cartilage loss in OA.

Two prior randomized, controlled trials provided conflicting evidence, he highlighted, with one study showing that supplementation of 2,000 IU/day of vitamin D for 2 years had no effect on symptoms or knee structure (JAMA 2013;309:155-62) while another showed that a monthly dose of 60,000 IU for 1 year may be beneficial in terms of relieving pain and functional outcomes but longer follow-up was required (Clin. Orthop. Relat. Res. 2013;471:3556-62).

The VIDEO study was therefore designed to try to resolve some of the controversy and look at a larger group of patients for a longer period of time. The study’s hypothesis was that vitamin D might ease knee pain and perhaps have effect structural changes in patients with symptomatic knee OA who had low vitamin D levels. A low vitamin D level was defined as a serum measurement of 25(OH)D of 12.5-60 nmol/L (5-24 ng/mL) at baseline.

Of almost 600 patients screened, 413 were randomized, with 209 randomized to the oral vitamin D supplementation group and 204 to the matched placebo arm. Patients in each group had comparable characteristics at baseline, with a mean age of around 62 to ­63 years. Half the patients were female. Baseline serum vitamin D levels were about 43 nmol/L (17.2 ng/mL). Virtually all (96%) of patients had radiographic evidence of knee OA, 97% had cartilage defects, and 80% had bone marrow lesions.

While serum levels of 25(OH)D were successfully increased in the supplemented patients over the course of the study, this did not translate into an improvement in the coprimary endpoint of a change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain over 24 months. The difference in WOMAC pain between the vitamin D and placebo groups was a nonsignifcant –14.8 (–49.9 vs. –35.1; P = .102). Vitamin D–supplemented patients did, however, report marginally less VAS pain (–14.8 vs. –9.4; P = .038).

Total tibial cartilage volume loss, the second coprimary endpoint, was not significantly different between the vitamin D and placebo groups, at around 121 and 150 mm³ per annum, with 2-year changes of –3.44% vs. –4.23% per annum (P = .132). The secondary endpoints of changes in tibiofemoral cartilage defects (0.29 vs. 0.47; P = .159) and tibiofemoral BMLs (–0.59 vs. –0.21; P = .087) were also not significantly different, but patients randomized to vitamin D supplementation had fewer increases in BMLs (17% vs. 27%; P = .03).

There was no concern over the safety of vitamin D supplementation, although more general side effects were noted in the vitamin D vs. the placebo group.

Commenting on the strengths and weaknesses of the study, Mr. Jin noted it was a large, multicenter, randomized, double-blind, placebo-controlled trial with a reasonably long follow-up. The patient group studied has good generalizability to those seen in everyday practice, he suggested, noting that the main limitation was the number of patients lost to follow-up because of noncompliance: 21 patients in the vitamin D group vs. 8 patients in the placebo group.

ROME – Vitamin D supplementation did not ease osteoarthritic knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index in a 2-year, randomized, double-blind, placebo-controlled trial.

Results of the VIDEO (Vitamin D Effect on Osteoarthritis) study in patients with symptomatic knee osteoarthritis (OA) and low vitamin D levels also showed that replenishing vitamin D also had no effect on the loss of cartilage volume, although there might be a marginal benefit on bone marrow lesions (BMLs) and pain assessed using a visual analog scale (VAS).

“Vitamin D at 50,000 IU/month over 2 years did not meet the primary endpoint in this randomized, controlled trial,” said Jason Jin, a Ph.D. candidate at the Menzies Research Institute, University of Tasmania in Hobart, Australia, who presented the VIDEO study findings at the European Congress of Rheumatology.

He cited a recent commentary published in the Journal of the American Medical Association (JAMA 2015;313:1311-12) that looked at vitamin D research and clinical practice in which the authors said that “clinical enthusiasm for supplemental vitamin D has outpaced available evidence.” This seems to be true considering the results of this and other previous randomized trials, Mr. Jin observed.

“The background of this study is that, in the last decade, vitamin D has become a hot topic in osteoarthritis research and epidemiologic studies have found that vitamin D deficiency is very common in knee osteoarthritis patients,” he said. Low levels of vitamin D have been linked to increased knee pain, radiographic progression, and increased cartilage loss in OA.

Two prior randomized, controlled trials provided conflicting evidence, he highlighted, with one study showing that supplementation of 2,000 IU/day of vitamin D for 2 years had no effect on symptoms or knee structure (JAMA 2013;309:155-62) while another showed that a monthly dose of 60,000 IU for 1 year may be beneficial in terms of relieving pain and functional outcomes but longer follow-up was required (Clin. Orthop. Relat. Res. 2013;471:3556-62).

The VIDEO study was therefore designed to try to resolve some of the controversy and look at a larger group of patients for a longer period of time. The study’s hypothesis was that vitamin D might ease knee pain and perhaps have effect structural changes in patients with symptomatic knee OA who had low vitamin D levels. A low vitamin D level was defined as a serum measurement of 25(OH)D of 12.5-60 nmol/L (5-24 ng/mL) at baseline.

Of almost 600 patients screened, 413 were randomized, with 209 randomized to the oral vitamin D supplementation group and 204 to the matched placebo arm. Patients in each group had comparable characteristics at baseline, with a mean age of around 62 to ­63 years. Half the patients were female. Baseline serum vitamin D levels were about 43 nmol/L (17.2 ng/mL). Virtually all (96%) of patients had radiographic evidence of knee OA, 97% had cartilage defects, and 80% had bone marrow lesions.

While serum levels of 25(OH)D were successfully increased in the supplemented patients over the course of the study, this did not translate into an improvement in the coprimary endpoint of a change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain over 24 months. The difference in WOMAC pain between the vitamin D and placebo groups was a nonsignifcant –14.8 (–49.9 vs. –35.1; P = .102). Vitamin D–supplemented patients did, however, report marginally less VAS pain (–14.8 vs. –9.4; P = .038).

Total tibial cartilage volume loss, the second coprimary endpoint, was not significantly different between the vitamin D and placebo groups, at around 121 and 150 mm³ per annum, with 2-year changes of –3.44% vs. –4.23% per annum (P = .132). The secondary endpoints of changes in tibiofemoral cartilage defects (0.29 vs. 0.47; P = .159) and tibiofemoral BMLs (–0.59 vs. –0.21; P = .087) were also not significantly different, but patients randomized to vitamin D supplementation had fewer increases in BMLs (17% vs. 27%; P = .03).

There was no concern over the safety of vitamin D supplementation, although more general side effects were noted in the vitamin D vs. the placebo group.

Commenting on the strengths and weaknesses of the study, Mr. Jin noted it was a large, multicenter, randomized, double-blind, placebo-controlled trial with a reasonably long follow-up. The patient group studied has good generalizability to those seen in everyday practice, he suggested, noting that the main limitation was the number of patients lost to follow-up because of noncompliance: 21 patients in the vitamin D group vs. 8 patients in the placebo group.

ROME – Vitamin D supplementation did not ease osteoarthritic knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index in a 2-year, randomized, double-blind, placebo-controlled trial.

Results of the VIDEO (Vitamin D Effect on Osteoarthritis) study in patients with symptomatic knee osteoarthritis (OA) and low vitamin D levels also showed that replenishing vitamin D also had no effect on the loss of cartilage volume, although there might be a marginal benefit on bone marrow lesions (BMLs) and pain assessed using a visual analog scale (VAS).

“Vitamin D at 50,000 IU/month over 2 years did not meet the primary endpoint in this randomized, controlled trial,” said Jason Jin, a Ph.D. candidate at the Menzies Research Institute, University of Tasmania in Hobart, Australia, who presented the VIDEO study findings at the European Congress of Rheumatology.

He cited a recent commentary published in the Journal of the American Medical Association (JAMA 2015;313:1311-12) that looked at vitamin D research and clinical practice in which the authors said that “clinical enthusiasm for supplemental vitamin D has outpaced available evidence.” This seems to be true considering the results of this and other previous randomized trials, Mr. Jin observed.

“The background of this study is that, in the last decade, vitamin D has become a hot topic in osteoarthritis research and epidemiologic studies have found that vitamin D deficiency is very common in knee osteoarthritis patients,” he said. Low levels of vitamin D have been linked to increased knee pain, radiographic progression, and increased cartilage loss in OA.

Two prior randomized, controlled trials provided conflicting evidence, he highlighted, with one study showing that supplementation of 2,000 IU/day of vitamin D for 2 years had no effect on symptoms or knee structure (JAMA 2013;309:155-62) while another showed that a monthly dose of 60,000 IU for 1 year may be beneficial in terms of relieving pain and functional outcomes but longer follow-up was required (Clin. Orthop. Relat. Res. 2013;471:3556-62).

The VIDEO study was therefore designed to try to resolve some of the controversy and look at a larger group of patients for a longer period of time. The study’s hypothesis was that vitamin D might ease knee pain and perhaps have effect structural changes in patients with symptomatic knee OA who had low vitamin D levels. A low vitamin D level was defined as a serum measurement of 25(OH)D of 12.5-60 nmol/L (5-24 ng/mL) at baseline.

Of almost 600 patients screened, 413 were randomized, with 209 randomized to the oral vitamin D supplementation group and 204 to the matched placebo arm. Patients in each group had comparable characteristics at baseline, with a mean age of around 62 to ­63 years. Half the patients were female. Baseline serum vitamin D levels were about 43 nmol/L (17.2 ng/mL). Virtually all (96%) of patients had radiographic evidence of knee OA, 97% had cartilage defects, and 80% had bone marrow lesions.

While serum levels of 25(OH)D were successfully increased in the supplemented patients over the course of the study, this did not translate into an improvement in the coprimary endpoint of a change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain over 24 months. The difference in WOMAC pain between the vitamin D and placebo groups was a nonsignifcant –14.8 (–49.9 vs. –35.1; P = .102). Vitamin D–supplemented patients did, however, report marginally less VAS pain (–14.8 vs. –9.4; P = .038).

Total tibial cartilage volume loss, the second coprimary endpoint, was not significantly different between the vitamin D and placebo groups, at around 121 and 150 mm³ per annum, with 2-year changes of –3.44% vs. –4.23% per annum (P = .132). The secondary endpoints of changes in tibiofemoral cartilage defects (0.29 vs. 0.47; P = .159) and tibiofemoral BMLs (–0.59 vs. –0.21; P = .087) were also not significantly different, but patients randomized to vitamin D supplementation had fewer increases in BMLs (17% vs. 27%; P = .03).

There was no concern over the safety of vitamin D supplementation, although more general side effects were noted in the vitamin D vs. the placebo group.

Commenting on the strengths and weaknesses of the study, Mr. Jin noted it was a large, multicenter, randomized, double-blind, placebo-controlled trial with a reasonably long follow-up. The patient group studied has good generalizability to those seen in everyday practice, he suggested, noting that the main limitation was the number of patients lost to follow-up because of noncompliance: 21 patients in the vitamin D group vs. 8 patients in the placebo group.

ROME – Tumor necrosis factor inhibitors remain the mainstay of treatment for patients with psoriatic arthritis who don’t fully respond to treatment with a nonsteroidal anti-inflammatory drug and at least one conventional synthetic disease-modifying antirheumatic drug in newly updated treatment recommendations written by a task force of the European League Against Rheumatism.

The revised recommendations for psoriatic arthritis (PsA) replace what EULAR had last released in 2011 and published in 2012 (Ann. Rheum. Dis. 2012;71:4-12) and also add three new drug options not mentioned in the 2011 version that the panel now endorsed as alternatives to a tumor necrosis factor (TNF) inhibitor when a TNF inhibitor is not appropriate. The three additions are ustekinumab (Stelara), which acts by inhibiting interleukin- (IL-)12 and IL-23, secukinumab (Cosentyx), which acts by inhibiting IL-17, and apremilast (Otezla), which inhibits phosphodiesterase-4. Ustekinumab and secukinumab are considered biological disease-modifying antirheumatic drugs (bDMARDs), like the TNF inhibitors, while apremilast occupies a new classification niche as a targeted synthetic DMARD, said Dr. Laure Gossec, convener of the PsA treatment task force, at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

Although ustekinumab, secukinumab, and apremilast all have a role to play in managing selected PsA patients, they all remain second line to TNF inhibitors, stressed Dr. Gossec, professor of rheumatology at Pierre and Marie Curie University in Paris. A TNF inhibitor is the first agent to turn to when treatment with an NSAID and a conventional synthetic DMARD fails to bring about remission or minimal disease activity essentially because of its much longer track record of safety and efficacy, she said. Specifically, TNF inhibitors have been studied long term and have demonstrated their safety in registries, they have not been surpassed for efficacy by any other agent using indirect comparisons, and now that biosimilar TNF inhibitors have entered the market they also could potentially offer a price advantage, compared with newer agents.

But for some patients, TNF inhibitors are not appropriate, such as a patient with certain comorbidities or a history of infections that would make a TNF inhibitor contraindicated, she said. For these patients, one of the other types of biologic DMARDS now available would be the top alternative. In other patients, a comorbidity profile or a history of infections might make any biologic DMARD contraindicated, in which case the targeted synthetic DMARD apremilast is an appropriate alternative, she said.

The revised recommendations contain several other new items:

• For patients with active enthesitis, dactylitis, or both and an insufficient response to an NSAID or local glucocorticoid injections, then a TNF inhibitor or alternatively an IL-12 and IL-23 inhibitor (currently ustekinumab) or an IL-17 inhibitor (currently secukinumab) may be considered. Conventional synthetic DMARDS are ineffective for these patients, while in contrast all of the biologic DMARDs are effective, but the TNF inhibitors have an edge because of greater experience with the class in this setting.

• For patients with predominantly axial disease that is active and insufficiently responsive to NSAID treatment, a biologic DMARD should be considered, specifically a TNF inhibitor. Conventional synthetic DMARDs also have no efficacy for these patients, and few data exist regarding the efficacy of IL-12 and IL-23 inhibitors or IL-17 inhibitors.

• When patients fail to respond adequately to one biologic DMARD, switching to another biologic DMARD should be considered. This could involve switching from one TNF inhibitor to another, as some evidence exists that this could be effective. Alternatively, it could involve switching to a IL-12 and IL-23 inhibitor, an IL-17 inhibitor, or possibly a targeted synthetic DMARD (currently apremilast). The task force did not endorse any particular order of these drugs when switching occurs.

Dr. Gossec has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Novartis, Pfizer, Roche, and UCB.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Tumor necrosis factor inhibitors remain the mainstay of treatment for patients with psoriatic arthritis who don’t fully respond to treatment with a nonsteroidal anti-inflammatory drug and at least one conventional synthetic disease-modifying antirheumatic drug in newly updated treatment recommendations written by a task force of the European League Against Rheumatism.

The revised recommendations for psoriatic arthritis (PsA) replace what EULAR had last released in 2011 and published in 2012 (Ann. Rheum. Dis. 2012;71:4-12) and also add three new drug options not mentioned in the 2011 version that the panel now endorsed as alternatives to a tumor necrosis factor (TNF) inhibitor when a TNF inhibitor is not appropriate. The three additions are ustekinumab (Stelara), which acts by inhibiting interleukin- (IL-)12 and IL-23, secukinumab (Cosentyx), which acts by inhibiting IL-17, and apremilast (Otezla), which inhibits phosphodiesterase-4. Ustekinumab and secukinumab are considered biological disease-modifying antirheumatic drugs (bDMARDs), like the TNF inhibitors, while apremilast occupies a new classification niche as a targeted synthetic DMARD, said Dr. Laure Gossec, convener of the PsA treatment task force, at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

Although ustekinumab, secukinumab, and apremilast all have a role to play in managing selected PsA patients, they all remain second line to TNF inhibitors, stressed Dr. Gossec, professor of rheumatology at Pierre and Marie Curie University in Paris. A TNF inhibitor is the first agent to turn to when treatment with an NSAID and a conventional synthetic DMARD fails to bring about remission or minimal disease activity essentially because of its much longer track record of safety and efficacy, she said. Specifically, TNF inhibitors have been studied long term and have demonstrated their safety in registries, they have not been surpassed for efficacy by any other agent using indirect comparisons, and now that biosimilar TNF inhibitors have entered the market they also could potentially offer a price advantage, compared with newer agents.

But for some patients, TNF inhibitors are not appropriate, such as a patient with certain comorbidities or a history of infections that would make a TNF inhibitor contraindicated, she said. For these patients, one of the other types of biologic DMARDS now available would be the top alternative. In other patients, a comorbidity profile or a history of infections might make any biologic DMARD contraindicated, in which case the targeted synthetic DMARD apremilast is an appropriate alternative, she said.

The revised recommendations contain several other new items:

• For patients with active enthesitis, dactylitis, or both and an insufficient response to an NSAID or local glucocorticoid injections, then a TNF inhibitor or alternatively an IL-12 and IL-23 inhibitor (currently ustekinumab) or an IL-17 inhibitor (currently secukinumab) may be considered. Conventional synthetic DMARDS are ineffective for these patients, while in contrast all of the biologic DMARDs are effective, but the TNF inhibitors have an edge because of greater experience with the class in this setting.

• For patients with predominantly axial disease that is active and insufficiently responsive to NSAID treatment, a biologic DMARD should be considered, specifically a TNF inhibitor. Conventional synthetic DMARDs also have no efficacy for these patients, and few data exist regarding the efficacy of IL-12 and IL-23 inhibitors or IL-17 inhibitors.

• When patients fail to respond adequately to one biologic DMARD, switching to another biologic DMARD should be considered. This could involve switching from one TNF inhibitor to another, as some evidence exists that this could be effective. Alternatively, it could involve switching to a IL-12 and IL-23 inhibitor, an IL-17 inhibitor, or possibly a targeted synthetic DMARD (currently apremilast). The task force did not endorse any particular order of these drugs when switching occurs.

Dr. Gossec has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Novartis, Pfizer, Roche, and UCB.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Tumor necrosis factor inhibitors remain the mainstay of treatment for patients with psoriatic arthritis who don’t fully respond to treatment with a nonsteroidal anti-inflammatory drug and at least one conventional synthetic disease-modifying antirheumatic drug in newly updated treatment recommendations written by a task force of the European League Against Rheumatism.

The revised recommendations for psoriatic arthritis (PsA) replace what EULAR had last released in 2011 and published in 2012 (Ann. Rheum. Dis. 2012;71:4-12) and also add three new drug options not mentioned in the 2011 version that the panel now endorsed as alternatives to a tumor necrosis factor (TNF) inhibitor when a TNF inhibitor is not appropriate. The three additions are ustekinumab (Stelara), which acts by inhibiting interleukin- (IL-)12 and IL-23, secukinumab (Cosentyx), which acts by inhibiting IL-17, and apremilast (Otezla), which inhibits phosphodiesterase-4. Ustekinumab and secukinumab are considered biological disease-modifying antirheumatic drugs (bDMARDs), like the TNF inhibitors, while apremilast occupies a new classification niche as a targeted synthetic DMARD, said Dr. Laure Gossec, convener of the PsA treatment task force, at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

Although ustekinumab, secukinumab, and apremilast all have a role to play in managing selected PsA patients, they all remain second line to TNF inhibitors, stressed Dr. Gossec, professor of rheumatology at Pierre and Marie Curie University in Paris. A TNF inhibitor is the first agent to turn to when treatment with an NSAID and a conventional synthetic DMARD fails to bring about remission or minimal disease activity essentially because of its much longer track record of safety and efficacy, she said. Specifically, TNF inhibitors have been studied long term and have demonstrated their safety in registries, they have not been surpassed for efficacy by any other agent using indirect comparisons, and now that biosimilar TNF inhibitors have entered the market they also could potentially offer a price advantage, compared with newer agents.

But for some patients, TNF inhibitors are not appropriate, such as a patient with certain comorbidities or a history of infections that would make a TNF inhibitor contraindicated, she said. For these patients, one of the other types of biologic DMARDS now available would be the top alternative. In other patients, a comorbidity profile or a history of infections might make any biologic DMARD contraindicated, in which case the targeted synthetic DMARD apremilast is an appropriate alternative, she said.

The revised recommendations contain several other new items:

• For patients with active enthesitis, dactylitis, or both and an insufficient response to an NSAID or local glucocorticoid injections, then a TNF inhibitor or alternatively an IL-12 and IL-23 inhibitor (currently ustekinumab) or an IL-17 inhibitor (currently secukinumab) may be considered. Conventional synthetic DMARDS are ineffective for these patients, while in contrast all of the biologic DMARDs are effective, but the TNF inhibitors have an edge because of greater experience with the class in this setting.

• For patients with predominantly axial disease that is active and insufficiently responsive to NSAID treatment, a biologic DMARD should be considered, specifically a TNF inhibitor. Conventional synthetic DMARDs also have no efficacy for these patients, and few data exist regarding the efficacy of IL-12 and IL-23 inhibitors or IL-17 inhibitors.

• When patients fail to respond adequately to one biologic DMARD, switching to another biologic DMARD should be considered. This could involve switching from one TNF inhibitor to another, as some evidence exists that this could be effective. Alternatively, it could involve switching to a IL-12 and IL-23 inhibitor, an IL-17 inhibitor, or possibly a targeted synthetic DMARD (currently apremilast). The task force did not endorse any particular order of these drugs when switching occurs.

Dr. Gossec has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Novartis, Pfizer, Roche, and UCB.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Obese people had a 50% increased rate of developing rheumatoid arthritis compared with normal or underweight people, in a case-control study of more than 2,000 Swedish residents for which researchers used prospectively collected data.

The increased rate of developing rheumatoid arthritis (RA) conferred by obesity occurred in both women and in men, it was greatest in the subgroup of people who developed RA symptoms when they were age 50 years or younger, and it was greatest in the subgroup of people seropositive for anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), or both Dr. Lotta Ljung said at the European Congress of Rheumatology.

The findings add to the growing body of evidence documenting obesity as a risk factor for development of RA, said Dr. Ljung, a rheumatologist at Umeå (Sweden) University.

She and her associates used data collected in two Swedish population-based cohorts followed prospectively, the Västerbotten Intervention Programme and the Northern Sweden portion of the MONICA project. The two databases included baseline and long-term follow-up data during 1985-2013 from more than 110,000 Swedish citizens, average age 52 years at baseline, and average body mass index of 26 kg/m². The databases included 557 patients with incident RA, which appeared an average of 6 years following entry into their database, with 83% of the cases showing seropositivity for ACPA, RF, or both. The researchers matched these cases on a 3:1 basis with 1,671 controls without RA by their sex, year of birth, cohort, examination year, and region of residence in Sweden.

Mitchel L. Zoler/Frontline Medical News

In an analysis that controlled for both smoking and education level, people who entered one of the databases with a BMI of 30 kg/m² or higher, defined as obesity, had a statistically significant 50% increased rate of developing RA during follow-up, compared with people who entered with a BMI of less than 25 kg/m², which corresponded to normal- or under-weight. Those with a BMI of 25-29.99 kg/m², the overweight group, had a borderline statistically significant 20% increased rate of developing RA during follow-up, compared with the reference group, Dr. Ljung reported.

An analysis that examined the link between incident RA and baseline BMI as a continuous variable showed a 2% increased rate of incident RA for each 1-unit increase in BMI, but this relationship fell short of statistical significance after adjustment for smoking and education level. A second analysis that looked at waist circumference as a continuous variable showed a statistically significant 2% rise in RA incidence for each 1-cm increase in waist circumference at baseline after adjustment.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

*Correction, 7/7/15: An earlier version of this article misstated information in the Vitals section.

ROME – Obese people had a 50% increased rate of developing rheumatoid arthritis compared with normal or underweight people, in a case-control study of more than 2,000 Swedish residents for which researchers used prospectively collected data.

The increased rate of developing rheumatoid arthritis (RA) conferred by obesity occurred in both women and in men, it was greatest in the subgroup of people who developed RA symptoms when they were age 50 years or younger, and it was greatest in the subgroup of people seropositive for anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), or both Dr. Lotta Ljung said at the European Congress of Rheumatology.

The findings add to the growing body of evidence documenting obesity as a risk factor for development of RA, said Dr. Ljung, a rheumatologist at Umeå (Sweden) University.

She and her associates used data collected in two Swedish population-based cohorts followed prospectively, the Västerbotten Intervention Programme and the Northern Sweden portion of the MONICA project. The two databases included baseline and long-term follow-up data during 1985-2013 from more than 110,000 Swedish citizens, average age 52 years at baseline, and average body mass index of 26 kg/m². The databases included 557 patients with incident RA, which appeared an average of 6 years following entry into their database, with 83% of the cases showing seropositivity for ACPA, RF, or both. The researchers matched these cases on a 3:1 basis with 1,671 controls without RA by their sex, year of birth, cohort, examination year, and region of residence in Sweden.

Mitchel L. Zoler/Frontline Medical News

In an analysis that controlled for both smoking and education level, people who entered one of the databases with a BMI of 30 kg/m² or higher, defined as obesity, had a statistically significant 50% increased rate of developing RA during follow-up, compared with people who entered with a BMI of less than 25 kg/m², which corresponded to normal- or under-weight. Those with a BMI of 25-29.99 kg/m², the overweight group, had a borderline statistically significant 20% increased rate of developing RA during follow-up, compared with the reference group, Dr. Ljung reported.

An analysis that examined the link between incident RA and baseline BMI as a continuous variable showed a 2% increased rate of incident RA for each 1-unit increase in BMI, but this relationship fell short of statistical significance after adjustment for smoking and education level. A second analysis that looked at waist circumference as a continuous variable showed a statistically significant 2% rise in RA incidence for each 1-cm increase in waist circumference at baseline after adjustment.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

*Correction, 7/7/15: An earlier version of this article misstated information in the Vitals section.

ROME – Obese people had a 50% increased rate of developing rheumatoid arthritis compared with normal or underweight people, in a case-control study of more than 2,000 Swedish residents for which researchers used prospectively collected data.

The increased rate of developing rheumatoid arthritis (RA) conferred by obesity occurred in both women and in men, it was greatest in the subgroup of people who developed RA symptoms when they were age 50 years or younger, and it was greatest in the subgroup of people seropositive for anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), or both Dr. Lotta Ljung said at the European Congress of Rheumatology.

The findings add to the growing body of evidence documenting obesity as a risk factor for development of RA, said Dr. Ljung, a rheumatologist at Umeå (Sweden) University.

She and her associates used data collected in two Swedish population-based cohorts followed prospectively, the Västerbotten Intervention Programme and the Northern Sweden portion of the MONICA project. The two databases included baseline and long-term follow-up data during 1985-2013 from more than 110,000 Swedish citizens, average age 52 years at baseline, and average body mass index of 26 kg/m². The databases included 557 patients with incident RA, which appeared an average of 6 years following entry into their database, with 83% of the cases showing seropositivity for ACPA, RF, or both. The researchers matched these cases on a 3:1 basis with 1,671 controls without RA by their sex, year of birth, cohort, examination year, and region of residence in Sweden.

Mitchel L. Zoler/Frontline Medical News

In an analysis that controlled for both smoking and education level, people who entered one of the databases with a BMI of 30 kg/m² or higher, defined as obesity, had a statistically significant 50% increased rate of developing RA during follow-up, compared with people who entered with a BMI of less than 25 kg/m², which corresponded to normal- or under-weight. Those with a BMI of 25-29.99 kg/m², the overweight group, had a borderline statistically significant 20% increased rate of developing RA during follow-up, compared with the reference group, Dr. Ljung reported.

An analysis that examined the link between incident RA and baseline BMI as a continuous variable showed a 2% increased rate of incident RA for each 1-unit increase in BMI, but this relationship fell short of statistical significance after adjustment for smoking and education level. A second analysis that looked at waist circumference as a continuous variable showed a statistically significant 2% rise in RA incidence for each 1-cm increase in waist circumference at baseline after adjustment.

mzoler@frontlinemedcom.com

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*Correction, 7/7/15: An earlier version of this article misstated information in the Vitals section.