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Cervical cancer incidence declines after age 85
Women should stop attending their cervical screening appointments at the recommended age of 65 and over only if they have an adequate prior screening history with negative results, researchers have warned.
“Messages about a ‘stopping age’ should emphasize the recommendation for an adequate screening history of previous negative tests before screening is discontinued, not just chronological age,” wrote the study authors. The report was published in the American Journal of Preventive Medicine (2017 May 1. doi: 10.1016/j.amepre.2017.02.024).
Leading professional organizations recommend “average-risk” women should be screened for cervical cancer between the ages of 21 and 65 years.
However, the authors, led by Mary C. White, ScD, of the Centers for Disease Control and Prevention, Atlanta, and her colleagues noted that data from 2013 showed that one-fifth of cervical cancer deaths occurred in women in the United States who were over the age of 65 years.
In the current study, the research team looked at data from the cross-sectional household National Health Interview Surveys from 2013 and 2015 to determine the number of women aged 41-70 years who had never had a Pap test or had not had one for 5 years or more.
After correcting for women who had undergone a hysterectomy, the researchers found that the incidence rate for cervical cancer increased with age until about 70 years and then declined after the age of 85.
Yet the proportion of women who had not been screened recently increased with age, from about 12% for women in their 40s to nearly 24% for women aged 66-70 years.
Efforts should be made to clarify misperceptions about the risk of cervical cancer among older women and health care providers, the investigators said.
“A recommended upper age limit for routine screening may lead women and providers to assume that cervical cancer is a younger woman’s disease,” they said.
Catch-up screening might be needed for underscreened women after the age of 65 years, although the physical and psychological issues associated with this should be taken into account, the study authors said.
“Age itself may need to be reconsidered, given high cervical cancer incidence rates after the age of 65 years, increases in life expectancy, and different human papillomavirus exposures by birth cohort,” they concluded.
Women should stop attending their cervical screening appointments at the recommended age of 65 and over only if they have an adequate prior screening history with negative results, researchers have warned.
“Messages about a ‘stopping age’ should emphasize the recommendation for an adequate screening history of previous negative tests before screening is discontinued, not just chronological age,” wrote the study authors. The report was published in the American Journal of Preventive Medicine (2017 May 1. doi: 10.1016/j.amepre.2017.02.024).
Leading professional organizations recommend “average-risk” women should be screened for cervical cancer between the ages of 21 and 65 years.
However, the authors, led by Mary C. White, ScD, of the Centers for Disease Control and Prevention, Atlanta, and her colleagues noted that data from 2013 showed that one-fifth of cervical cancer deaths occurred in women in the United States who were over the age of 65 years.
In the current study, the research team looked at data from the cross-sectional household National Health Interview Surveys from 2013 and 2015 to determine the number of women aged 41-70 years who had never had a Pap test or had not had one for 5 years or more.
After correcting for women who had undergone a hysterectomy, the researchers found that the incidence rate for cervical cancer increased with age until about 70 years and then declined after the age of 85.
Yet the proportion of women who had not been screened recently increased with age, from about 12% for women in their 40s to nearly 24% for women aged 66-70 years.
Efforts should be made to clarify misperceptions about the risk of cervical cancer among older women and health care providers, the investigators said.
“A recommended upper age limit for routine screening may lead women and providers to assume that cervical cancer is a younger woman’s disease,” they said.
Catch-up screening might be needed for underscreened women after the age of 65 years, although the physical and psychological issues associated with this should be taken into account, the study authors said.
“Age itself may need to be reconsidered, given high cervical cancer incidence rates after the age of 65 years, increases in life expectancy, and different human papillomavirus exposures by birth cohort,” they concluded.
Women should stop attending their cervical screening appointments at the recommended age of 65 and over only if they have an adequate prior screening history with negative results, researchers have warned.
“Messages about a ‘stopping age’ should emphasize the recommendation for an adequate screening history of previous negative tests before screening is discontinued, not just chronological age,” wrote the study authors. The report was published in the American Journal of Preventive Medicine (2017 May 1. doi: 10.1016/j.amepre.2017.02.024).
Leading professional organizations recommend “average-risk” women should be screened for cervical cancer between the ages of 21 and 65 years.
However, the authors, led by Mary C. White, ScD, of the Centers for Disease Control and Prevention, Atlanta, and her colleagues noted that data from 2013 showed that one-fifth of cervical cancer deaths occurred in women in the United States who were over the age of 65 years.
In the current study, the research team looked at data from the cross-sectional household National Health Interview Surveys from 2013 and 2015 to determine the number of women aged 41-70 years who had never had a Pap test or had not had one for 5 years or more.
After correcting for women who had undergone a hysterectomy, the researchers found that the incidence rate for cervical cancer increased with age until about 70 years and then declined after the age of 85.
Yet the proportion of women who had not been screened recently increased with age, from about 12% for women in their 40s to nearly 24% for women aged 66-70 years.
Efforts should be made to clarify misperceptions about the risk of cervical cancer among older women and health care providers, the investigators said.
“A recommended upper age limit for routine screening may lead women and providers to assume that cervical cancer is a younger woman’s disease,” they said.
Catch-up screening might be needed for underscreened women after the age of 65 years, although the physical and psychological issues associated with this should be taken into account, the study authors said.
“Age itself may need to be reconsidered, given high cervical cancer incidence rates after the age of 65 years, increases in life expectancy, and different human papillomavirus exposures by birth cohort,” they concluded.
FROM THE AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Key clinical point: Women should stop cervical cancer screening at the recommended age of 65 only if they have an adequate prior history of negative tests.
Major finding: The incidence rate for cervical cancer increases with age until about 70 years and then declines after the age of 85. Yet data show the proportion of women who have not recently been screened for cervical cancer increases with age (12% for women in their 40s vs. 24% for women aged 66-70 years).
Data source: Analysis of data from the cross-sectional household National Health Interview Surveys from 2013 and 2015.
Disclosures: No relevant disclosures were reported by the authors.
Short course of prednisolone may help distinguish between RA and hand OA
A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.
However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).
For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.
The pilot part of the TryCort study involved 15 patients with confirmed osteoarthritis and 15 with rheumatoid arthritis who were given 1 g of paracetamol (acetaminophen) a day for 5 days, and on days 3-5, they were given a 20-mg dose of prednisolone (Arthritis Res Ther. 2017;19:73. doi: 10.1186/s13075-017-1279-z).
Results showed that the patients with RA had greater improvements in their pain scores (0-10 on a numerical rating scale), compared with OA patients. The mean percentage improvement in pain scores at day 5 was 52.3% in the RA group and 22.0% in the OA group.
The research team considered that a 40% improvement in pain scores was the best choice between sensitivity and specificity regarding a diagnosis of RA.
At this 40% improvement cut-off, the “pred-test” was positive in 11 patients with RA and in four patients with OA (P = .012), with a sensitivity and specificity for a diagnosis of RA of 73.3% for both measures.
In order to validate the test, the researchers enrolled 95 patients with pain in their fingers and hands but without a clear diagnosis. These patients completed the 5-day intervention, and then at week 12 a rheumatologist diagnosed 47 as having RA and 48 were thought to not have RA.
The patients with diagnosed RA had a higher reduction in pain scores during the treatment with prednisolone, compared with patients without RA.
The median percentage of improvement at day 5 was higher in patients with RA than in those without RA (50% [interquartile range, 30%-60%] vs. 20% [IQR, 10%-30%]; P = .001). Overall, 40 of the 95 patients had an improvement of more than 40% in pain levels on day 5, fulfilling the criteria of a positive pred-test.
However, the authors noted that 31 patients with RA had a positive pred-test (77.5%), compared with nine (22.5%) patients without RA (P greater than .001).
The sensitivity of the pred-test for a diagnosis of RA was 0.6 (95% confidence interval, 0.5-0.8) and the specificity was 0.8 (95% CI, 0.7-0.9). The positive and negative predictive values were 0.77 and 0.70, respectively.
The authors concluded that the pred-test “performed well” but not “perfectly well.”
“We are aware that the pred-test without confirmation of other surrogate markers is not helpful in clinical decision-making processes,” they said. “We, therefore, recommend use of the test in light of other confirming factors, such as history, physical examination, imaging, and laboratory results.”
The test could be used to triage patients from primary care to rheumatologist care, they suggested.
The study was financially supported by Rheumazentrum Ruhrgebiet. The authors declared no conflicts of interest.
A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.
However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).
For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.
The pilot part of the TryCort study involved 15 patients with confirmed osteoarthritis and 15 with rheumatoid arthritis who were given 1 g of paracetamol (acetaminophen) a day for 5 days, and on days 3-5, they were given a 20-mg dose of prednisolone (Arthritis Res Ther. 2017;19:73. doi: 10.1186/s13075-017-1279-z).
Results showed that the patients with RA had greater improvements in their pain scores (0-10 on a numerical rating scale), compared with OA patients. The mean percentage improvement in pain scores at day 5 was 52.3% in the RA group and 22.0% in the OA group.
The research team considered that a 40% improvement in pain scores was the best choice between sensitivity and specificity regarding a diagnosis of RA.
At this 40% improvement cut-off, the “pred-test” was positive in 11 patients with RA and in four patients with OA (P = .012), with a sensitivity and specificity for a diagnosis of RA of 73.3% for both measures.
In order to validate the test, the researchers enrolled 95 patients with pain in their fingers and hands but without a clear diagnosis. These patients completed the 5-day intervention, and then at week 12 a rheumatologist diagnosed 47 as having RA and 48 were thought to not have RA.
The patients with diagnosed RA had a higher reduction in pain scores during the treatment with prednisolone, compared with patients without RA.
The median percentage of improvement at day 5 was higher in patients with RA than in those without RA (50% [interquartile range, 30%-60%] vs. 20% [IQR, 10%-30%]; P = .001). Overall, 40 of the 95 patients had an improvement of more than 40% in pain levels on day 5, fulfilling the criteria of a positive pred-test.
However, the authors noted that 31 patients with RA had a positive pred-test (77.5%), compared with nine (22.5%) patients without RA (P greater than .001).
The sensitivity of the pred-test for a diagnosis of RA was 0.6 (95% confidence interval, 0.5-0.8) and the specificity was 0.8 (95% CI, 0.7-0.9). The positive and negative predictive values were 0.77 and 0.70, respectively.
The authors concluded that the pred-test “performed well” but not “perfectly well.”
“We are aware that the pred-test without confirmation of other surrogate markers is not helpful in clinical decision-making processes,” they said. “We, therefore, recommend use of the test in light of other confirming factors, such as history, physical examination, imaging, and laboratory results.”
The test could be used to triage patients from primary care to rheumatologist care, they suggested.
The study was financially supported by Rheumazentrum Ruhrgebiet. The authors declared no conflicts of interest.
A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.
However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).
For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.
The pilot part of the TryCort study involved 15 patients with confirmed osteoarthritis and 15 with rheumatoid arthritis who were given 1 g of paracetamol (acetaminophen) a day for 5 days, and on days 3-5, they were given a 20-mg dose of prednisolone (Arthritis Res Ther. 2017;19:73. doi: 10.1186/s13075-017-1279-z).
Results showed that the patients with RA had greater improvements in their pain scores (0-10 on a numerical rating scale), compared with OA patients. The mean percentage improvement in pain scores at day 5 was 52.3% in the RA group and 22.0% in the OA group.
The research team considered that a 40% improvement in pain scores was the best choice between sensitivity and specificity regarding a diagnosis of RA.
At this 40% improvement cut-off, the “pred-test” was positive in 11 patients with RA and in four patients with OA (P = .012), with a sensitivity and specificity for a diagnosis of RA of 73.3% for both measures.
In order to validate the test, the researchers enrolled 95 patients with pain in their fingers and hands but without a clear diagnosis. These patients completed the 5-day intervention, and then at week 12 a rheumatologist diagnosed 47 as having RA and 48 were thought to not have RA.
The patients with diagnosed RA had a higher reduction in pain scores during the treatment with prednisolone, compared with patients without RA.
The median percentage of improvement at day 5 was higher in patients with RA than in those without RA (50% [interquartile range, 30%-60%] vs. 20% [IQR, 10%-30%]; P = .001). Overall, 40 of the 95 patients had an improvement of more than 40% in pain levels on day 5, fulfilling the criteria of a positive pred-test.
However, the authors noted that 31 patients with RA had a positive pred-test (77.5%), compared with nine (22.5%) patients without RA (P greater than .001).
The sensitivity of the pred-test for a diagnosis of RA was 0.6 (95% confidence interval, 0.5-0.8) and the specificity was 0.8 (95% CI, 0.7-0.9). The positive and negative predictive values were 0.77 and 0.70, respectively.
The authors concluded that the pred-test “performed well” but not “perfectly well.”
“We are aware that the pred-test without confirmation of other surrogate markers is not helpful in clinical decision-making processes,” they said. “We, therefore, recommend use of the test in light of other confirming factors, such as history, physical examination, imaging, and laboratory results.”
The test could be used to triage patients from primary care to rheumatologist care, they suggested.
The study was financially supported by Rheumazentrum Ruhrgebiet. The authors declared no conflicts of interest.
FROM ARTHRITIS RESEARCH & THERAPY
Key clinical point:
Major finding: The sensitivity of the pred-test for a diagnosis of RA was 0.6 (95% CI, 0.5-0.8) and the specificity was 0.8 (95% CI, 0.7-0.9).
Data source: A pilot study of 20 mg of prednisolone for 3 days in 30 patients with established RA or OA followed by a validation study of the test in 95 patients with pain in their fingers and hands but without a clear diagnosis.
Disclosures: The study was financially supported by Rheumazentrum Ruhrgebiet. The authors declared no conflicts of interest.
Triple therapy found as ‘durable’ as biologic after methotrexate failure
People with active rheumatoid arthritis who have a suboptimal response to methotrexate and then switch to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine do just as well and stay on treatment just as long as do those who switch to methotrexate and etanercept, a follow-up study to the RACAT trial shows.
Although evidence shows that patients do well on combination disease-modifying antirheumatic drugs (DMARDs) following methotrexate failure, many rheumatologists still prefer to add a tumor necrosis factor inhibitor such as etanercept, wrote first author Shana M. Peper, MD, of the University of Nebraska, Omaha, and her colleagues (Arthritis Care Res. 2017 Apr 7. doi: 10.1002/acr.23255).
The observational, follow-up study involved 289 patients with active rheumatoid arthritis with a suboptimal response to methotrexate who had participated in the 48-week, multicenter, double-blind, Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial and then consented to an additional 72 weeks of open-label extended follow-up during which patients and their physicians were free to change or continue treatment. At the end of the double-blind portion, 145 were receiving triple therapy with the conventional DMARDs and 144 were receiving combination therapy with methotrexate and etanercept.
In the RACAT trial, the primary outcome was the 48-week change in 28-joint Disease Activity Score (DAS28). At 24 weeks, patients in both groups who had an inadequate response to their assigned therapy (defined by a change in DAS28 of less than 1.2) were switched to the other treatment arm in a blinded fashion.
After 1 year, 78% of patients on triple therapy remained on it, compared with 63% of patients who began the extended follow-up on the methotrexate-etanercept combination and remained on it.
More patients switched from methotrexate-etanercept to triple therapy than the other way around (P = .005), but when the researchers removed patients who switched at the start of the extended follow-up from the analysis, continuation rates were nearly identical. The results also did not change when the researchers performed analyses using only the patients who did not switch therapy at week 24 during the blinded trial and again with patients assigned to their original randomized groups.
Average DAS28 scores were similar for each group (3.8 ± 1.4 for triple therapy vs. 3.5 ± 1.3 for methotrexate-etanercept) and remained similar at follow-up. There were also no differences between swollen or tender joint counts, patient global health assessments, or erythrocyte sedimentation rates between the groups.
“Triple therapy remained at least as durable and effective as its biologic counterpart,” the authors concluded.
“Our findings suggest that the majority of patients with active disease despite methotrexate respond to triple therapy and will continue to do so with excellent tolerability,” they wrote.
The findings also supported the approach of reserving more costly biologics for patients who continue to have disease progression despite combination conventional DMARD therapy, they added.
The authors reported no relevant funding for the follow-up analysis. One author reported having consulted for Pfizer and received research support from Bristol-Myers Squibb and AstraZeneca. Another author reported having consulted for Medac, Antares, Lilly, Coherus, and GlaxoSmithKline.
People with active rheumatoid arthritis who have a suboptimal response to methotrexate and then switch to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine do just as well and stay on treatment just as long as do those who switch to methotrexate and etanercept, a follow-up study to the RACAT trial shows.
Although evidence shows that patients do well on combination disease-modifying antirheumatic drugs (DMARDs) following methotrexate failure, many rheumatologists still prefer to add a tumor necrosis factor inhibitor such as etanercept, wrote first author Shana M. Peper, MD, of the University of Nebraska, Omaha, and her colleagues (Arthritis Care Res. 2017 Apr 7. doi: 10.1002/acr.23255).
The observational, follow-up study involved 289 patients with active rheumatoid arthritis with a suboptimal response to methotrexate who had participated in the 48-week, multicenter, double-blind, Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial and then consented to an additional 72 weeks of open-label extended follow-up during which patients and their physicians were free to change or continue treatment. At the end of the double-blind portion, 145 were receiving triple therapy with the conventional DMARDs and 144 were receiving combination therapy with methotrexate and etanercept.
In the RACAT trial, the primary outcome was the 48-week change in 28-joint Disease Activity Score (DAS28). At 24 weeks, patients in both groups who had an inadequate response to their assigned therapy (defined by a change in DAS28 of less than 1.2) were switched to the other treatment arm in a blinded fashion.
After 1 year, 78% of patients on triple therapy remained on it, compared with 63% of patients who began the extended follow-up on the methotrexate-etanercept combination and remained on it.
More patients switched from methotrexate-etanercept to triple therapy than the other way around (P = .005), but when the researchers removed patients who switched at the start of the extended follow-up from the analysis, continuation rates were nearly identical. The results also did not change when the researchers performed analyses using only the patients who did not switch therapy at week 24 during the blinded trial and again with patients assigned to their original randomized groups.
Average DAS28 scores were similar for each group (3.8 ± 1.4 for triple therapy vs. 3.5 ± 1.3 for methotrexate-etanercept) and remained similar at follow-up. There were also no differences between swollen or tender joint counts, patient global health assessments, or erythrocyte sedimentation rates between the groups.
“Triple therapy remained at least as durable and effective as its biologic counterpart,” the authors concluded.
“Our findings suggest that the majority of patients with active disease despite methotrexate respond to triple therapy and will continue to do so with excellent tolerability,” they wrote.
The findings also supported the approach of reserving more costly biologics for patients who continue to have disease progression despite combination conventional DMARD therapy, they added.
The authors reported no relevant funding for the follow-up analysis. One author reported having consulted for Pfizer and received research support from Bristol-Myers Squibb and AstraZeneca. Another author reported having consulted for Medac, Antares, Lilly, Coherus, and GlaxoSmithKline.
People with active rheumatoid arthritis who have a suboptimal response to methotrexate and then switch to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine do just as well and stay on treatment just as long as do those who switch to methotrexate and etanercept, a follow-up study to the RACAT trial shows.
Although evidence shows that patients do well on combination disease-modifying antirheumatic drugs (DMARDs) following methotrexate failure, many rheumatologists still prefer to add a tumor necrosis factor inhibitor such as etanercept, wrote first author Shana M. Peper, MD, of the University of Nebraska, Omaha, and her colleagues (Arthritis Care Res. 2017 Apr 7. doi: 10.1002/acr.23255).
The observational, follow-up study involved 289 patients with active rheumatoid arthritis with a suboptimal response to methotrexate who had participated in the 48-week, multicenter, double-blind, Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial and then consented to an additional 72 weeks of open-label extended follow-up during which patients and their physicians were free to change or continue treatment. At the end of the double-blind portion, 145 were receiving triple therapy with the conventional DMARDs and 144 were receiving combination therapy with methotrexate and etanercept.
In the RACAT trial, the primary outcome was the 48-week change in 28-joint Disease Activity Score (DAS28). At 24 weeks, patients in both groups who had an inadequate response to their assigned therapy (defined by a change in DAS28 of less than 1.2) were switched to the other treatment arm in a blinded fashion.
After 1 year, 78% of patients on triple therapy remained on it, compared with 63% of patients who began the extended follow-up on the methotrexate-etanercept combination and remained on it.
More patients switched from methotrexate-etanercept to triple therapy than the other way around (P = .005), but when the researchers removed patients who switched at the start of the extended follow-up from the analysis, continuation rates were nearly identical. The results also did not change when the researchers performed analyses using only the patients who did not switch therapy at week 24 during the blinded trial and again with patients assigned to their original randomized groups.
Average DAS28 scores were similar for each group (3.8 ± 1.4 for triple therapy vs. 3.5 ± 1.3 for methotrexate-etanercept) and remained similar at follow-up. There were also no differences between swollen or tender joint counts, patient global health assessments, or erythrocyte sedimentation rates between the groups.
“Triple therapy remained at least as durable and effective as its biologic counterpart,” the authors concluded.
“Our findings suggest that the majority of patients with active disease despite methotrexate respond to triple therapy and will continue to do so with excellent tolerability,” they wrote.
The findings also supported the approach of reserving more costly biologics for patients who continue to have disease progression despite combination conventional DMARD therapy, they added.
The authors reported no relevant funding for the follow-up analysis. One author reported having consulted for Pfizer and received research support from Bristol-Myers Squibb and AstraZeneca. Another author reported having consulted for Medac, Antares, Lilly, Coherus, and GlaxoSmithKline.
Key clinical point:
Major finding: At 1 year, people with active RA with a suboptimal response to methotrexate were just as likely to remain on triple DMARD therapy as they were on etanercept plus methotrexate.
Data source: An observational follow-up study of 289 patients with RA who had participated in the 48-week, multicenter, double-blind, RACAT trial.
Disclosures: The authors reported no relevant funding for the follow-up analysis. One author reported having consulted for Pfizer and received research support from Bristol-Myers Squibb and AstraZeneca. Another author reported having consulted for Medac, Antares, Lilly, Coherus, and GlaxoSmithKline.
Osteoarthritis’ link to metabolic syndrome tied to body weight, BMI
The metabolic syndrome’s association with the development of osteoarthritis appears to occur primarily through the influence of factors related to body weight or body mass index, according to an analysis of data from the longitudinal Framingham osteoarthritis study.
Jingbo Niu, DSc, of the Clinical Epidemiology Research and Training Unit at Boston University, and her colleagues found that while the presence of the metabolic syndrome (MetS) and its individual components – central obesity, dyslipidemia, impaired fasting glucose, and hypertension – were associated with a risk of both radiographic osteoarthritis (ROA) and symptomatic OA (SxOA), all associations besides high blood pressure (particularly diastolic blood pressure) disappeared after they adjusted for body mass index (BMI) or body weight (Arthritis Rheumatol. 2017 Mar 3. doi: 10.1002/art.40087).
The research team analyzed 991 participants of the 1992-1995 Framingham Offspring Cohort who did not have existing OA at baseline. Average age was 54.2 years; 55.1% were women. According to Adult Treatment Panel III criteria, 27% of the men and 23% of the women had MetS. Those who had MetS were older, had a higher BMI, and were less likely to drink alcohol or have a college education.
In 2002-2005, the cohort underwent follow-up for the presence of OA. The incidence of ROA in the cohort was 9.8% (78 of 800 knees) in men and 10.5% (105 of 1,003 knees) in women. ROA occurred when a knee without previous radiographic evidence of OA developed a Kellgren and Lawrence score of 2 or higher, and SxOA occurred when a knee developed ROA together with knee pain.
After adjusting for age, education, smoking status, alcohol consumption, and physical activity, the researchers found that MetS, abdominal obesity, and low high-density lipoprotein cholesterol were significantly associated with incident ROA among men. Among women, abdominal obesity and high blood pressure were associated with incident ROA, while MetS was not. However, after adjustment for body weight or BMI, none of the associations remained significant.
The incidence of SxOA was 6.3% (53 of 837 knees) in men and 7.2% (75 of 1,037 knees) in women. Incident SxOA was significantly associated with MetS in women and with the MetS components of abdominal obesity and high blood pressure in both men and women before adjustment for BMI or body weight. However, only an association between diastolic blood pressure and incident SxOA persisted in both sexes after adjustment for body weight, the study authors noted.
“High blood pressure is another MetS component associated with OA in previous studies before adjusting for BMI ... While we found [diastolic blood pressure] was related to incident SxOA even after adjustment for BMI, the relation of [systolic blood pressure] and incident SxOA was nearly significant also, suggesting that both might be related to SxOA,” the study authors wrote.
But a cross-sectional analysis of the relationship would be challenging to interpret, they said, since treatment for SxOA included NSAIDs, which are known to raise blood pressure.
The National Institutes of Health supported the study. The authors declared having no conflicts of interest.
The OA incidence reported in the Framingham study is particularly noteworthy because it shows that preexisting MetS and its components are risk factors for subsequent symptomatic OA and not just radiographic OA, which seems to indicate the existence of common risk factors for both MetS and OA in a manner such that OA could be just a late-occurring component of MetS.
But it may be most appropriate to consider metabolic OA as a complication of MetS, similar to cardiovascular disease.
The fact that any component of MetS remained significantly associated with symptomatic OA after adjustment for BMI and body weight argued strongly for a metabolic driver of OA pathophysiology when considering the likely confounding of body weight between mechanical and metabolic processes.
Nevertheless, carefully designed studies are needed to determine the relative impact of increased body mass in MetS on joint loading versus metabolic derangements, including systemic inflammation, to rule in or out the effects of altered metabolism on incident OA risk independent of biomechanics.
This knowledge would help a great deal toward understanding metabolic OA and other phenotypes as well as for the development of rational treatment approaches.
Thomas Appleton, MD, PhD, of Western University in London, Ont., and his colleagues made these comments in an editorial (Arthritis Rheumatol. 2017 Mar 7. doi: 10.1002/art.40089). They declared having no conflicts of interest to relevant to their editorial.
The OA incidence reported in the Framingham study is particularly noteworthy because it shows that preexisting MetS and its components are risk factors for subsequent symptomatic OA and not just radiographic OA, which seems to indicate the existence of common risk factors for both MetS and OA in a manner such that OA could be just a late-occurring component of MetS.
But it may be most appropriate to consider metabolic OA as a complication of MetS, similar to cardiovascular disease.
The fact that any component of MetS remained significantly associated with symptomatic OA after adjustment for BMI and body weight argued strongly for a metabolic driver of OA pathophysiology when considering the likely confounding of body weight between mechanical and metabolic processes.
Nevertheless, carefully designed studies are needed to determine the relative impact of increased body mass in MetS on joint loading versus metabolic derangements, including systemic inflammation, to rule in or out the effects of altered metabolism on incident OA risk independent of biomechanics.
This knowledge would help a great deal toward understanding metabolic OA and other phenotypes as well as for the development of rational treatment approaches.
Thomas Appleton, MD, PhD, of Western University in London, Ont., and his colleagues made these comments in an editorial (Arthritis Rheumatol. 2017 Mar 7. doi: 10.1002/art.40089). They declared having no conflicts of interest to relevant to their editorial.
The OA incidence reported in the Framingham study is particularly noteworthy because it shows that preexisting MetS and its components are risk factors for subsequent symptomatic OA and not just radiographic OA, which seems to indicate the existence of common risk factors for both MetS and OA in a manner such that OA could be just a late-occurring component of MetS.
But it may be most appropriate to consider metabolic OA as a complication of MetS, similar to cardiovascular disease.
The fact that any component of MetS remained significantly associated with symptomatic OA after adjustment for BMI and body weight argued strongly for a metabolic driver of OA pathophysiology when considering the likely confounding of body weight between mechanical and metabolic processes.
Nevertheless, carefully designed studies are needed to determine the relative impact of increased body mass in MetS on joint loading versus metabolic derangements, including systemic inflammation, to rule in or out the effects of altered metabolism on incident OA risk independent of biomechanics.
This knowledge would help a great deal toward understanding metabolic OA and other phenotypes as well as for the development of rational treatment approaches.
Thomas Appleton, MD, PhD, of Western University in London, Ont., and his colleagues made these comments in an editorial (Arthritis Rheumatol. 2017 Mar 7. doi: 10.1002/art.40089). They declared having no conflicts of interest to relevant to their editorial.
The metabolic syndrome’s association with the development of osteoarthritis appears to occur primarily through the influence of factors related to body weight or body mass index, according to an analysis of data from the longitudinal Framingham osteoarthritis study.
Jingbo Niu, DSc, of the Clinical Epidemiology Research and Training Unit at Boston University, and her colleagues found that while the presence of the metabolic syndrome (MetS) and its individual components – central obesity, dyslipidemia, impaired fasting glucose, and hypertension – were associated with a risk of both radiographic osteoarthritis (ROA) and symptomatic OA (SxOA), all associations besides high blood pressure (particularly diastolic blood pressure) disappeared after they adjusted for body mass index (BMI) or body weight (Arthritis Rheumatol. 2017 Mar 3. doi: 10.1002/art.40087).
The research team analyzed 991 participants of the 1992-1995 Framingham Offspring Cohort who did not have existing OA at baseline. Average age was 54.2 years; 55.1% were women. According to Adult Treatment Panel III criteria, 27% of the men and 23% of the women had MetS. Those who had MetS were older, had a higher BMI, and were less likely to drink alcohol or have a college education.
In 2002-2005, the cohort underwent follow-up for the presence of OA. The incidence of ROA in the cohort was 9.8% (78 of 800 knees) in men and 10.5% (105 of 1,003 knees) in women. ROA occurred when a knee without previous radiographic evidence of OA developed a Kellgren and Lawrence score of 2 or higher, and SxOA occurred when a knee developed ROA together with knee pain.
After adjusting for age, education, smoking status, alcohol consumption, and physical activity, the researchers found that MetS, abdominal obesity, and low high-density lipoprotein cholesterol were significantly associated with incident ROA among men. Among women, abdominal obesity and high blood pressure were associated with incident ROA, while MetS was not. However, after adjustment for body weight or BMI, none of the associations remained significant.
The incidence of SxOA was 6.3% (53 of 837 knees) in men and 7.2% (75 of 1,037 knees) in women. Incident SxOA was significantly associated with MetS in women and with the MetS components of abdominal obesity and high blood pressure in both men and women before adjustment for BMI or body weight. However, only an association between diastolic blood pressure and incident SxOA persisted in both sexes after adjustment for body weight, the study authors noted.
“High blood pressure is another MetS component associated with OA in previous studies before adjusting for BMI ... While we found [diastolic blood pressure] was related to incident SxOA even after adjustment for BMI, the relation of [systolic blood pressure] and incident SxOA was nearly significant also, suggesting that both might be related to SxOA,” the study authors wrote.
But a cross-sectional analysis of the relationship would be challenging to interpret, they said, since treatment for SxOA included NSAIDs, which are known to raise blood pressure.
The National Institutes of Health supported the study. The authors declared having no conflicts of interest.
The metabolic syndrome’s association with the development of osteoarthritis appears to occur primarily through the influence of factors related to body weight or body mass index, according to an analysis of data from the longitudinal Framingham osteoarthritis study.
Jingbo Niu, DSc, of the Clinical Epidemiology Research and Training Unit at Boston University, and her colleagues found that while the presence of the metabolic syndrome (MetS) and its individual components – central obesity, dyslipidemia, impaired fasting glucose, and hypertension – were associated with a risk of both radiographic osteoarthritis (ROA) and symptomatic OA (SxOA), all associations besides high blood pressure (particularly diastolic blood pressure) disappeared after they adjusted for body mass index (BMI) or body weight (Arthritis Rheumatol. 2017 Mar 3. doi: 10.1002/art.40087).
The research team analyzed 991 participants of the 1992-1995 Framingham Offspring Cohort who did not have existing OA at baseline. Average age was 54.2 years; 55.1% were women. According to Adult Treatment Panel III criteria, 27% of the men and 23% of the women had MetS. Those who had MetS were older, had a higher BMI, and were less likely to drink alcohol or have a college education.
In 2002-2005, the cohort underwent follow-up for the presence of OA. The incidence of ROA in the cohort was 9.8% (78 of 800 knees) in men and 10.5% (105 of 1,003 knees) in women. ROA occurred when a knee without previous radiographic evidence of OA developed a Kellgren and Lawrence score of 2 or higher, and SxOA occurred when a knee developed ROA together with knee pain.
After adjusting for age, education, smoking status, alcohol consumption, and physical activity, the researchers found that MetS, abdominal obesity, and low high-density lipoprotein cholesterol were significantly associated with incident ROA among men. Among women, abdominal obesity and high blood pressure were associated with incident ROA, while MetS was not. However, after adjustment for body weight or BMI, none of the associations remained significant.
The incidence of SxOA was 6.3% (53 of 837 knees) in men and 7.2% (75 of 1,037 knees) in women. Incident SxOA was significantly associated with MetS in women and with the MetS components of abdominal obesity and high blood pressure in both men and women before adjustment for BMI or body weight. However, only an association between diastolic blood pressure and incident SxOA persisted in both sexes after adjustment for body weight, the study authors noted.
“High blood pressure is another MetS component associated with OA in previous studies before adjusting for BMI ... While we found [diastolic blood pressure] was related to incident SxOA even after adjustment for BMI, the relation of [systolic blood pressure] and incident SxOA was nearly significant also, suggesting that both might be related to SxOA,” the study authors wrote.
But a cross-sectional analysis of the relationship would be challenging to interpret, they said, since treatment for SxOA included NSAIDs, which are known to raise blood pressure.
The National Institutes of Health supported the study. The authors declared having no conflicts of interest.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: There is no strong association between the metabolic syndrome (MetS) and OA after adjustment for BMI or body weight.
Major finding: Components of MetS were initially associated with incident radiographic and symptomatic OA, but after adjustment for BMI or body weight, most of the associations were weak and insignificant. However, an association between the MetS and high blood pressure persisted in both sexes.
Data source: An analysis of 991 participants of the 1992-1995 Framingham Offspring Cohort who did not have existing OA at baseline and were followed for 10 years.
Disclosures: The National Institutes of Health supported the study. The authors declared having no conflicts of interest.
Biomarker score not predictive of successful TNF inhibitor tapering in RA
A multi-biomarker disease activity score in patients with longstanding rheumatoid arthritis and low disease activity prior to tapering adalimumab or etanercept did not predict flare-related outcomes in an 18-month, open-label, randomized clinical trial.
These findings seemed “robust and valid, at least in this specific context,” said investigators led by Chantal A. M. Bouman, MD, of Sint Maartenskliniek Nijmegen (the Netherlands), because multiple other outcomes measured in the trial, including discontinuation of biologic and radiographic progression, were not predicted by the multi-biomarker disease activity (MBDA) score, which is derived from an algorithm using a biomarker panel of 12 serum proteins and is marketed under the name Vectra DA.
The researchers sought to determine if measurement of disease activity using biomarkers with the MBDA score has a potential for smaller measurement error, compared with clinical decision making, in predicting the effects of dose tapering of biologic disease-modifying antirheumatic drugs by examining blood samples taken from 171 people with longstanding RA with low disease activity who were participating in the Dutch Dose Reduction Strategies of Subcutaneous TNF inhibitors (DRESS) trial (Rheumatology [Oxford]. 2017 Feb 22. doi: 10.1093/rheumatology/kex003).
The use of biomarkers could potentially overcome some of the drawbacks of the most widely used and extensively validated measure of RA disease activity, the Disease Activity Score in 28 joints (DAS28), which relies on “clinical assessments [that] are subject to interobserver variability, resulting in measurement error and suboptimal precision,” the investigators wrote. “Also, DAS28 can be influenced by factors other than RA disease activity (e.g., OA, [fibromyalgia], or other causes of inflammation, such an infection), resulting in clinical misclassification of disease activity state.”
The randomized DRESS trial investigated the noninferiority of a dose reduction strategy of adalimumab or etanercept (n = 115), compared with usual care (n = 56), on the rate of flare, defined as a DAS28 (using C-reactive protein) increase of more than 1.2 or 0.6 if the current DAS was more than or equal to 3.2. A major flare was one lasting more than 3 months despite treatment intervention.
The baseline MBDA score did not predict successful tapering based on an area under the receiver operating characteristic (AUROC) of 0.53 (95% confidence interval, 0.41-0.66), nor did it predict the discontinuation of either biologic (AUROC = 0.51; 95% CI, 0.36-0.66) or the occurrence of flare (AUROC = 0.50; 95% CI, 0.41-0.59 for both groups combined) or major flare (AUROC = 0.46; 95% CI, 0.32-0.65 for both groups combined).
Although the authors found a borderline positive predictive value of baseline MBDA score for major flare in the usual care group (AUROC = 0.72; 95% CI, 0.56-0.88), they said the finding should be “interpreted cautiously” as multiple testing may have resulted in false-positive findings.
The researchers also discovered that, in contrast to findings from five studies in four cohorts of patients with established or early RA, the MBDA did not predict radiographic progression (AUROC = 0.53 for predicting radiographic progression of more than 0.5 Sharp–van der Heijde points; 95% CI, 0.43-0.63 for both groups combined).
The inability of the MBDA score to predict radiographic outcomes “might be attributable to the low frequency and severity of radiographic progression in our study, with only a small difference in favor of the [usual care] group. It might reflect the strict tight control that was applied to patients who were already in low disease activity or remission,” the investigators suggested.
They also said that, in spite of the findings, the MBDA score may have predictive value in other groups of patients, such as those with early rheumatoid arthritis, higher disease activity, or suboptimal disease control, and suggested that the study’s findings be validated in further studies.
The study received no specific funding. However, one author is an employee of Crescendo Bioscience and reported receiving stock grants from its parent company, Myriad Genetics. Several authors reported relationships with industry.
A multi-biomarker disease activity score in patients with longstanding rheumatoid arthritis and low disease activity prior to tapering adalimumab or etanercept did not predict flare-related outcomes in an 18-month, open-label, randomized clinical trial.
These findings seemed “robust and valid, at least in this specific context,” said investigators led by Chantal A. M. Bouman, MD, of Sint Maartenskliniek Nijmegen (the Netherlands), because multiple other outcomes measured in the trial, including discontinuation of biologic and radiographic progression, were not predicted by the multi-biomarker disease activity (MBDA) score, which is derived from an algorithm using a biomarker panel of 12 serum proteins and is marketed under the name Vectra DA.
The researchers sought to determine if measurement of disease activity using biomarkers with the MBDA score has a potential for smaller measurement error, compared with clinical decision making, in predicting the effects of dose tapering of biologic disease-modifying antirheumatic drugs by examining blood samples taken from 171 people with longstanding RA with low disease activity who were participating in the Dutch Dose Reduction Strategies of Subcutaneous TNF inhibitors (DRESS) trial (Rheumatology [Oxford]. 2017 Feb 22. doi: 10.1093/rheumatology/kex003).
The use of biomarkers could potentially overcome some of the drawbacks of the most widely used and extensively validated measure of RA disease activity, the Disease Activity Score in 28 joints (DAS28), which relies on “clinical assessments [that] are subject to interobserver variability, resulting in measurement error and suboptimal precision,” the investigators wrote. “Also, DAS28 can be influenced by factors other than RA disease activity (e.g., OA, [fibromyalgia], or other causes of inflammation, such an infection), resulting in clinical misclassification of disease activity state.”
The randomized DRESS trial investigated the noninferiority of a dose reduction strategy of adalimumab or etanercept (n = 115), compared with usual care (n = 56), on the rate of flare, defined as a DAS28 (using C-reactive protein) increase of more than 1.2 or 0.6 if the current DAS was more than or equal to 3.2. A major flare was one lasting more than 3 months despite treatment intervention.
The baseline MBDA score did not predict successful tapering based on an area under the receiver operating characteristic (AUROC) of 0.53 (95% confidence interval, 0.41-0.66), nor did it predict the discontinuation of either biologic (AUROC = 0.51; 95% CI, 0.36-0.66) or the occurrence of flare (AUROC = 0.50; 95% CI, 0.41-0.59 for both groups combined) or major flare (AUROC = 0.46; 95% CI, 0.32-0.65 for both groups combined).
Although the authors found a borderline positive predictive value of baseline MBDA score for major flare in the usual care group (AUROC = 0.72; 95% CI, 0.56-0.88), they said the finding should be “interpreted cautiously” as multiple testing may have resulted in false-positive findings.
The researchers also discovered that, in contrast to findings from five studies in four cohorts of patients with established or early RA, the MBDA did not predict radiographic progression (AUROC = 0.53 for predicting radiographic progression of more than 0.5 Sharp–van der Heijde points; 95% CI, 0.43-0.63 for both groups combined).
The inability of the MBDA score to predict radiographic outcomes “might be attributable to the low frequency and severity of radiographic progression in our study, with only a small difference in favor of the [usual care] group. It might reflect the strict tight control that was applied to patients who were already in low disease activity or remission,” the investigators suggested.
They also said that, in spite of the findings, the MBDA score may have predictive value in other groups of patients, such as those with early rheumatoid arthritis, higher disease activity, or suboptimal disease control, and suggested that the study’s findings be validated in further studies.
The study received no specific funding. However, one author is an employee of Crescendo Bioscience and reported receiving stock grants from its parent company, Myriad Genetics. Several authors reported relationships with industry.
A multi-biomarker disease activity score in patients with longstanding rheumatoid arthritis and low disease activity prior to tapering adalimumab or etanercept did not predict flare-related outcomes in an 18-month, open-label, randomized clinical trial.
These findings seemed “robust and valid, at least in this specific context,” said investigators led by Chantal A. M. Bouman, MD, of Sint Maartenskliniek Nijmegen (the Netherlands), because multiple other outcomes measured in the trial, including discontinuation of biologic and radiographic progression, were not predicted by the multi-biomarker disease activity (MBDA) score, which is derived from an algorithm using a biomarker panel of 12 serum proteins and is marketed under the name Vectra DA.
The researchers sought to determine if measurement of disease activity using biomarkers with the MBDA score has a potential for smaller measurement error, compared with clinical decision making, in predicting the effects of dose tapering of biologic disease-modifying antirheumatic drugs by examining blood samples taken from 171 people with longstanding RA with low disease activity who were participating in the Dutch Dose Reduction Strategies of Subcutaneous TNF inhibitors (DRESS) trial (Rheumatology [Oxford]. 2017 Feb 22. doi: 10.1093/rheumatology/kex003).
The use of biomarkers could potentially overcome some of the drawbacks of the most widely used and extensively validated measure of RA disease activity, the Disease Activity Score in 28 joints (DAS28), which relies on “clinical assessments [that] are subject to interobserver variability, resulting in measurement error and suboptimal precision,” the investigators wrote. “Also, DAS28 can be influenced by factors other than RA disease activity (e.g., OA, [fibromyalgia], or other causes of inflammation, such an infection), resulting in clinical misclassification of disease activity state.”
The randomized DRESS trial investigated the noninferiority of a dose reduction strategy of adalimumab or etanercept (n = 115), compared with usual care (n = 56), on the rate of flare, defined as a DAS28 (using C-reactive protein) increase of more than 1.2 or 0.6 if the current DAS was more than or equal to 3.2. A major flare was one lasting more than 3 months despite treatment intervention.
The baseline MBDA score did not predict successful tapering based on an area under the receiver operating characteristic (AUROC) of 0.53 (95% confidence interval, 0.41-0.66), nor did it predict the discontinuation of either biologic (AUROC = 0.51; 95% CI, 0.36-0.66) or the occurrence of flare (AUROC = 0.50; 95% CI, 0.41-0.59 for both groups combined) or major flare (AUROC = 0.46; 95% CI, 0.32-0.65 for both groups combined).
Although the authors found a borderline positive predictive value of baseline MBDA score for major flare in the usual care group (AUROC = 0.72; 95% CI, 0.56-0.88), they said the finding should be “interpreted cautiously” as multiple testing may have resulted in false-positive findings.
The researchers also discovered that, in contrast to findings from five studies in four cohorts of patients with established or early RA, the MBDA did not predict radiographic progression (AUROC = 0.53 for predicting radiographic progression of more than 0.5 Sharp–van der Heijde points; 95% CI, 0.43-0.63 for both groups combined).
The inability of the MBDA score to predict radiographic outcomes “might be attributable to the low frequency and severity of radiographic progression in our study, with only a small difference in favor of the [usual care] group. It might reflect the strict tight control that was applied to patients who were already in low disease activity or remission,” the investigators suggested.
They also said that, in spite of the findings, the MBDA score may have predictive value in other groups of patients, such as those with early rheumatoid arthritis, higher disease activity, or suboptimal disease control, and suggested that the study’s findings be validated in further studies.
The study received no specific funding. However, one author is an employee of Crescendo Bioscience and reported receiving stock grants from its parent company, Myriad Genetics. Several authors reported relationships with industry.
FROM RHEUMATOLOGY
Key clinical point:
Main finding: The baseline MBDA score did not predict successful tapering based on an area under the receiver operating characteristic of 0.53 (95% CI, 0.41-0.66).
Data source: Analysis of serum samples from 171 RA patients taking part in the noninferiority, randomized, open-label, controlled Dose Reduction Strategies of Subcutaneous TNF inhibitors (DRESS) trial.
Disclosures: The study received no specific funding. However, one author is an employee of Crescendo Bioscience and reported receiving stock grants from its parent company, Myriad Genetics. Several authors reported relationships with industry.
Methotrexate use justified for early RA, disease prevention
Efforts to delay or prevent rheumatoid arthritis (RA) in individuals at high risk for the disease received a boost from the findings of a subgroup analysis of an older Dutch prevention trial involving methotrexate that were published recently in Arthritis & Rheumatology.
However, while the 22-patient subgroup analysis of the 2007 trial, called PROMPT (Probable RA: Methotrexate Versus Placebo Treatment), showed that 1 year of methotrexate prevented the development of rheumatoid arthritis in significantly more individuals at high risk for the disease than did placebo, hindsight has shown that most of these high-risk individuals actually had RA at baseline as defined by the 2010 American College or Rheumatology/European League Against Rheumatism classification criteria.
Even though the “landscape of RA has changed since this study was conceived, enrolled, and performed,” Dr. Sparks noted that the study provides evidence that today’s “standard of care really works” by making use of data that are unobtainable today.
“Nowadays, we wouldn’t be able to do a placebo-controlled trial in early RA because those patients need to be treated, but at the time, it was perfectly fine, based on the treatment landscape, to put these patients in a [placebo-controlled] trial,” he said in an interview.
“It also demonstrates that you really need to find high-risk individuals, because, if you recruit people who are never going to develop RA, you’re just diluting your effect, and you’re not going to find the difference in the groups based on that diluted effect when there could be a true effect in that special subgroup,” he added.
Senior study author Annette van der Helm-van Mil, MD, PhD, and her colleagues at Leiden (the Netherlands) University Medical Center performed the reanalysis after the initial finding that methotrexate had no preventative effect may have been falsely negative because the study included patients with a low risk of progressing to RA (Arthritis Rheumatol. 2017 Feb 19. doi: 10.1002/art.40062).
In the reanalysis, the investigators defined 22 out of the trial’s 110 participants as high risk based on their score of 8 or higher on the Leiden prediction rule at baseline. Of those 22, 18 also fulfilled the 2010 classification criteria for RA.
This “definition of high risk [in the trial] very much coincided with the new classification criteria and reinforces the standard of care that patients with new diagnosed RA should be treated with DMARDs [disease-modifying antirheumatic drugs] front line,” Dr. Sparks said.
The Leiden prediction rule score is based on ACPA statuses, as well as age, sex, distribution of involved joints, number of swollen and tender joints, severity of morning stiffness, C-reactive protein level, and rheumatoid factor. In previous studies of patients with undifferentiated arthritis, a score of 8 or higher with the prediction rule had a positive predictive value of 84% in patients with undifferentiated arthritis, according to the investigators.
Based on a primary outcome of fulfilling the 1987 classification criteria for RA after 5 years of follow-up, the investigators found that 6 of 11 (55%) in the methotrexate arm developed RA, compared with all 11 patients in the placebo arm (P = .011). “A 1-year course of methotrexate was associated with an absolute risk reduction of 45% on RA development, resulting in a number needed to treat of 2.2 (95% [confidence interval], 1.3-6.2),” the authors wrote.
Furthermore, the time to the development of RA based on the 1987 criteria was longer with methotrexate than with placebo (median of 22.5 months vs. 3 months; P less than .001).
Drug-free remission was also achieved by 4 of 11 (36%) patients taking methotrexate, compared with none of the patients taking placebo (P = .027).
The beneficial effects of methotrexate were seen in ACPA-positive and ACPA-negative high-risk patients but not in patients without a high risk of RA.
For the patients who did not fulfill the 2010 RA criteria at baseline, only one of four of those in the placebo arm did go on to develop RA based on 1987 criteria, whereas only one of three who received methotrexate did.
Overall, the reanalysis of PROMPT trial data illustrates how “noninformative inclusions can blur highly relevant study outcomes, such as prevention of RA,” the study authors concluded.
“As trials are now being conducted to evaluate the efficacy of treatment initiated in the phase of arthralgia, the development of adequate risk prediction models are of importance in order to prevent false-negative study results in the future,” they added.
The PROMPT trial was supported by the Dutch Arthritis Foundation and the Netherlands Organisation for Scientific Research.
Small numbers not withstanding, the findings of this reanalysis of the PROMPT trial are exciting, and they address the importance of identifying the right individuals to include in any type of prevention study in RA.
Given the temporal limits of clinical trials, inclusion criteria will need to incorporate both the likelihood of an important outcome and the timing of that outcome – right individuals, right time, right drug/intervention.
It is hoped that investigators will be able to demonstrate conclusively that preventive interventions work for rheumatic disease once these issues are addressed.
Kevin D. Deane, MD, PhD, and his coauthors are with the division of rheumatology at the University of Colorado, Denver, and made these remarks in an editorial accompanying the PROMPT trial reanalysis (Arthritis Rheumatol. 2017 Feb 19. doi: 10.1002/art.40061).
Small numbers not withstanding, the findings of this reanalysis of the PROMPT trial are exciting, and they address the importance of identifying the right individuals to include in any type of prevention study in RA.
Given the temporal limits of clinical trials, inclusion criteria will need to incorporate both the likelihood of an important outcome and the timing of that outcome – right individuals, right time, right drug/intervention.
It is hoped that investigators will be able to demonstrate conclusively that preventive interventions work for rheumatic disease once these issues are addressed.
Kevin D. Deane, MD, PhD, and his coauthors are with the division of rheumatology at the University of Colorado, Denver, and made these remarks in an editorial accompanying the PROMPT trial reanalysis (Arthritis Rheumatol. 2017 Feb 19. doi: 10.1002/art.40061).
Small numbers not withstanding, the findings of this reanalysis of the PROMPT trial are exciting, and they address the importance of identifying the right individuals to include in any type of prevention study in RA.
Given the temporal limits of clinical trials, inclusion criteria will need to incorporate both the likelihood of an important outcome and the timing of that outcome – right individuals, right time, right drug/intervention.
It is hoped that investigators will be able to demonstrate conclusively that preventive interventions work for rheumatic disease once these issues are addressed.
Kevin D. Deane, MD, PhD, and his coauthors are with the division of rheumatology at the University of Colorado, Denver, and made these remarks in an editorial accompanying the PROMPT trial reanalysis (Arthritis Rheumatol. 2017 Feb 19. doi: 10.1002/art.40061).
Efforts to delay or prevent rheumatoid arthritis (RA) in individuals at high risk for the disease received a boost from the findings of a subgroup analysis of an older Dutch prevention trial involving methotrexate that were published recently in Arthritis & Rheumatology.
However, while the 22-patient subgroup analysis of the 2007 trial, called PROMPT (Probable RA: Methotrexate Versus Placebo Treatment), showed that 1 year of methotrexate prevented the development of rheumatoid arthritis in significantly more individuals at high risk for the disease than did placebo, hindsight has shown that most of these high-risk individuals actually had RA at baseline as defined by the 2010 American College or Rheumatology/European League Against Rheumatism classification criteria.
Even though the “landscape of RA has changed since this study was conceived, enrolled, and performed,” Dr. Sparks noted that the study provides evidence that today’s “standard of care really works” by making use of data that are unobtainable today.
“Nowadays, we wouldn’t be able to do a placebo-controlled trial in early RA because those patients need to be treated, but at the time, it was perfectly fine, based on the treatment landscape, to put these patients in a [placebo-controlled] trial,” he said in an interview.
“It also demonstrates that you really need to find high-risk individuals, because, if you recruit people who are never going to develop RA, you’re just diluting your effect, and you’re not going to find the difference in the groups based on that diluted effect when there could be a true effect in that special subgroup,” he added.
Senior study author Annette van der Helm-van Mil, MD, PhD, and her colleagues at Leiden (the Netherlands) University Medical Center performed the reanalysis after the initial finding that methotrexate had no preventative effect may have been falsely negative because the study included patients with a low risk of progressing to RA (Arthritis Rheumatol. 2017 Feb 19. doi: 10.1002/art.40062).
In the reanalysis, the investigators defined 22 out of the trial’s 110 participants as high risk based on their score of 8 or higher on the Leiden prediction rule at baseline. Of those 22, 18 also fulfilled the 2010 classification criteria for RA.
This “definition of high risk [in the trial] very much coincided with the new classification criteria and reinforces the standard of care that patients with new diagnosed RA should be treated with DMARDs [disease-modifying antirheumatic drugs] front line,” Dr. Sparks said.
The Leiden prediction rule score is based on ACPA statuses, as well as age, sex, distribution of involved joints, number of swollen and tender joints, severity of morning stiffness, C-reactive protein level, and rheumatoid factor. In previous studies of patients with undifferentiated arthritis, a score of 8 or higher with the prediction rule had a positive predictive value of 84% in patients with undifferentiated arthritis, according to the investigators.
Based on a primary outcome of fulfilling the 1987 classification criteria for RA after 5 years of follow-up, the investigators found that 6 of 11 (55%) in the methotrexate arm developed RA, compared with all 11 patients in the placebo arm (P = .011). “A 1-year course of methotrexate was associated with an absolute risk reduction of 45% on RA development, resulting in a number needed to treat of 2.2 (95% [confidence interval], 1.3-6.2),” the authors wrote.
Furthermore, the time to the development of RA based on the 1987 criteria was longer with methotrexate than with placebo (median of 22.5 months vs. 3 months; P less than .001).
Drug-free remission was also achieved by 4 of 11 (36%) patients taking methotrexate, compared with none of the patients taking placebo (P = .027).
The beneficial effects of methotrexate were seen in ACPA-positive and ACPA-negative high-risk patients but not in patients without a high risk of RA.
For the patients who did not fulfill the 2010 RA criteria at baseline, only one of four of those in the placebo arm did go on to develop RA based on 1987 criteria, whereas only one of three who received methotrexate did.
Overall, the reanalysis of PROMPT trial data illustrates how “noninformative inclusions can blur highly relevant study outcomes, such as prevention of RA,” the study authors concluded.
“As trials are now being conducted to evaluate the efficacy of treatment initiated in the phase of arthralgia, the development of adequate risk prediction models are of importance in order to prevent false-negative study results in the future,” they added.
The PROMPT trial was supported by the Dutch Arthritis Foundation and the Netherlands Organisation for Scientific Research.
Efforts to delay or prevent rheumatoid arthritis (RA) in individuals at high risk for the disease received a boost from the findings of a subgroup analysis of an older Dutch prevention trial involving methotrexate that were published recently in Arthritis & Rheumatology.
However, while the 22-patient subgroup analysis of the 2007 trial, called PROMPT (Probable RA: Methotrexate Versus Placebo Treatment), showed that 1 year of methotrexate prevented the development of rheumatoid arthritis in significantly more individuals at high risk for the disease than did placebo, hindsight has shown that most of these high-risk individuals actually had RA at baseline as defined by the 2010 American College or Rheumatology/European League Against Rheumatism classification criteria.
Even though the “landscape of RA has changed since this study was conceived, enrolled, and performed,” Dr. Sparks noted that the study provides evidence that today’s “standard of care really works” by making use of data that are unobtainable today.
“Nowadays, we wouldn’t be able to do a placebo-controlled trial in early RA because those patients need to be treated, but at the time, it was perfectly fine, based on the treatment landscape, to put these patients in a [placebo-controlled] trial,” he said in an interview.
“It also demonstrates that you really need to find high-risk individuals, because, if you recruit people who are never going to develop RA, you’re just diluting your effect, and you’re not going to find the difference in the groups based on that diluted effect when there could be a true effect in that special subgroup,” he added.
Senior study author Annette van der Helm-van Mil, MD, PhD, and her colleagues at Leiden (the Netherlands) University Medical Center performed the reanalysis after the initial finding that methotrexate had no preventative effect may have been falsely negative because the study included patients with a low risk of progressing to RA (Arthritis Rheumatol. 2017 Feb 19. doi: 10.1002/art.40062).
In the reanalysis, the investigators defined 22 out of the trial’s 110 participants as high risk based on their score of 8 or higher on the Leiden prediction rule at baseline. Of those 22, 18 also fulfilled the 2010 classification criteria for RA.
This “definition of high risk [in the trial] very much coincided with the new classification criteria and reinforces the standard of care that patients with new diagnosed RA should be treated with DMARDs [disease-modifying antirheumatic drugs] front line,” Dr. Sparks said.
The Leiden prediction rule score is based on ACPA statuses, as well as age, sex, distribution of involved joints, number of swollen and tender joints, severity of morning stiffness, C-reactive protein level, and rheumatoid factor. In previous studies of patients with undifferentiated arthritis, a score of 8 or higher with the prediction rule had a positive predictive value of 84% in patients with undifferentiated arthritis, according to the investigators.
Based on a primary outcome of fulfilling the 1987 classification criteria for RA after 5 years of follow-up, the investigators found that 6 of 11 (55%) in the methotrexate arm developed RA, compared with all 11 patients in the placebo arm (P = .011). “A 1-year course of methotrexate was associated with an absolute risk reduction of 45% on RA development, resulting in a number needed to treat of 2.2 (95% [confidence interval], 1.3-6.2),” the authors wrote.
Furthermore, the time to the development of RA based on the 1987 criteria was longer with methotrexate than with placebo (median of 22.5 months vs. 3 months; P less than .001).
Drug-free remission was also achieved by 4 of 11 (36%) patients taking methotrexate, compared with none of the patients taking placebo (P = .027).
The beneficial effects of methotrexate were seen in ACPA-positive and ACPA-negative high-risk patients but not in patients without a high risk of RA.
For the patients who did not fulfill the 2010 RA criteria at baseline, only one of four of those in the placebo arm did go on to develop RA based on 1987 criteria, whereas only one of three who received methotrexate did.
Overall, the reanalysis of PROMPT trial data illustrates how “noninformative inclusions can blur highly relevant study outcomes, such as prevention of RA,” the study authors concluded.
“As trials are now being conducted to evaluate the efficacy of treatment initiated in the phase of arthralgia, the development of adequate risk prediction models are of importance in order to prevent false-negative study results in the future,” they added.
The PROMPT trial was supported by the Dutch Arthritis Foundation and the Netherlands Organisation for Scientific Research.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Main finding: In people deemed to be at high risk for RA, a 1-year course of methotrexate was associated with an absolute risk reduction of 45% of RA development, resulting in a number needed to treat of 2.2 (95% CI, 1.3-6.2).
Data source: A reanalysis of the PROMPT trial involving 110 patients with undifferentiated arthritis randomized to a 1-year course of methotrexate or placebo.
Disclosures: The PROMPT trial was supported by the Dutch Arthritis Foundation and the Netherlands Organisation for Scientific Research.
Rising arthritis prevalence driven by obesity
Rising obesity is driving an increase in arthritis prevalence, and the association is not appreciated because the impact of body mass index on joint disease is not fully understood, according to a study spanning four generations.
The proportion of people in more recent birth cohorts reporting arthritis symptoms indicates a successively greater prevalence of arthritis compared to earlier generations, based on an 18-year longitudinal study conducted by Elizabeth M. Badley, PhD, of Dalla Lana School of Public Health, University of Toronto, and her colleagues. The researchers compared the prevalence of arthritis across four birth cohorts: World War II (1935-1944; n = 1,598), older baby boomers (1945-1954; n = 2,208), younger baby boomers (1955-1964; n = 2,781) and Generation Xers (1965-1974; n = 2,230).
“Although our results do not represent projections as such, extrapolation of the trajectories of arthritis with age and comparison of the trajectories across cohorts suggest that current projections of the prevalence of arthritis … may be too low for obese individuals,” they concluded.
Using the World War II cohort as the reference group for comparison, the odds ratio for arthritis in Gen Xers was 3.2; for younger baby boomers it was 2.14; for older baby boomers, it was 1.48.
Furthermore, in all cohorts the age of onset of arthritis in obese individuals was earlier compared to those of normal weight.
“This has implications for the targeting of public health messages for the control and management of arthritis,” the researchers wrote (Arthritis Care Res. 2017. doi: 10.1002/acr.23213).
The authors noted that although the study participants were asked about arthritis in general it was likely the overall findings reflected an increasing prevalence of osteoarthritis.
And while the researchers could only speculate about the reasons for the higher prevalence of arthritis seen in recent cohorts, it was possible there had been “unrecognized changes over time in environmental or biologic exposures.”
The study was funded in part by a CIHR operating grant. No conflicts of interest were declared.
Rising obesity is driving an increase in arthritis prevalence, and the association is not appreciated because the impact of body mass index on joint disease is not fully understood, according to a study spanning four generations.
The proportion of people in more recent birth cohorts reporting arthritis symptoms indicates a successively greater prevalence of arthritis compared to earlier generations, based on an 18-year longitudinal study conducted by Elizabeth M. Badley, PhD, of Dalla Lana School of Public Health, University of Toronto, and her colleagues. The researchers compared the prevalence of arthritis across four birth cohorts: World War II (1935-1944; n = 1,598), older baby boomers (1945-1954; n = 2,208), younger baby boomers (1955-1964; n = 2,781) and Generation Xers (1965-1974; n = 2,230).
“Although our results do not represent projections as such, extrapolation of the trajectories of arthritis with age and comparison of the trajectories across cohorts suggest that current projections of the prevalence of arthritis … may be too low for obese individuals,” they concluded.
Using the World War II cohort as the reference group for comparison, the odds ratio for arthritis in Gen Xers was 3.2; for younger baby boomers it was 2.14; for older baby boomers, it was 1.48.
Furthermore, in all cohorts the age of onset of arthritis in obese individuals was earlier compared to those of normal weight.
“This has implications for the targeting of public health messages for the control and management of arthritis,” the researchers wrote (Arthritis Care Res. 2017. doi: 10.1002/acr.23213).
The authors noted that although the study participants were asked about arthritis in general it was likely the overall findings reflected an increasing prevalence of osteoarthritis.
And while the researchers could only speculate about the reasons for the higher prevalence of arthritis seen in recent cohorts, it was possible there had been “unrecognized changes over time in environmental or biologic exposures.”
The study was funded in part by a CIHR operating grant. No conflicts of interest were declared.
Rising obesity is driving an increase in arthritis prevalence, and the association is not appreciated because the impact of body mass index on joint disease is not fully understood, according to a study spanning four generations.
The proportion of people in more recent birth cohorts reporting arthritis symptoms indicates a successively greater prevalence of arthritis compared to earlier generations, based on an 18-year longitudinal study conducted by Elizabeth M. Badley, PhD, of Dalla Lana School of Public Health, University of Toronto, and her colleagues. The researchers compared the prevalence of arthritis across four birth cohorts: World War II (1935-1944; n = 1,598), older baby boomers (1945-1954; n = 2,208), younger baby boomers (1955-1964; n = 2,781) and Generation Xers (1965-1974; n = 2,230).
“Although our results do not represent projections as such, extrapolation of the trajectories of arthritis with age and comparison of the trajectories across cohorts suggest that current projections of the prevalence of arthritis … may be too low for obese individuals,” they concluded.
Using the World War II cohort as the reference group for comparison, the odds ratio for arthritis in Gen Xers was 3.2; for younger baby boomers it was 2.14; for older baby boomers, it was 1.48.
Furthermore, in all cohorts the age of onset of arthritis in obese individuals was earlier compared to those of normal weight.
“This has implications for the targeting of public health messages for the control and management of arthritis,” the researchers wrote (Arthritis Care Res. 2017. doi: 10.1002/acr.23213).
The authors noted that although the study participants were asked about arthritis in general it was likely the overall findings reflected an increasing prevalence of osteoarthritis.
And while the researchers could only speculate about the reasons for the higher prevalence of arthritis seen in recent cohorts, it was possible there had been “unrecognized changes over time in environmental or biologic exposures.”
The study was funded in part by a CIHR operating grant. No conflicts of interest were declared.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: The prevalence of arthritis in the general population is growing and increasing obesity appears to be a factor.
Major finding: When researchers used the World War II cohort as the reference group for comparison, the odds ratio for arthritis in Gen Xers was 3.2; for younger baby boomers it was 2.14; for older baby boomers, it was 1.48.
Data source: A longitudinal analysis of data from the 1994/95 to 2010/11 National Population Health survey that included 8,817 participants in four birth cohorts.
Disclosures: The study was funded in part by a CIHR operating grant. No conflicts of interest were declared.
Pilot trial of first in kind biologic shows RA treatment potential
The novel biologic mavrilimumab that targets the GM-CSF pathway has shown therapeutic potential in the treatment of rheumatoid arthritis in a proof-of-concept trial, particularly in patients who have failed to respond to biologics that target other pathways.
Writing in the Annals of the Rheumatic Diseases, researchers led by Gerd R. Burmester, MD, director and professor of medicine in the department of rheumatology and clinical immunology at Charité University Hospital and the Free University and Humboldt University of Berlin, noted that despite the success of the currently available biologics to treat rheumatoid arthritis (RA), a considerable number of patients do not achieve long-term responses (Ann Rheum Dis. 2017 Feb 17. doi: 10.1136/annrheumdis-2016-210624).
Mavrilimumab is a fully human monoclonal antibody that blocks GM-CSFR and is the first biologic of its kind to target the GM-CSF pathway, they noted.
The multicenter, phase IIb, randomized trial EARTH EXPLORER 1 involved 305 patients with moderate to severe RA who were randomized in a ratio of 1:1:1:1 to subcutaneous mavrilimumab 150 mg, 100 mg, 30 mg, or placebo every other week plus methotrexate for 24 weeks.
The results showed that the GM-CSFR blocker met one of its primary endpoints by significantly reducing the 28-joint Disease Activity Score based on C-reactive protein (DAS28–CRP) from baseline to week 12 when compared with placebo. The amount of reduction increased with the dose, from –1.37 with 30 mg, to –1.64 with 100 mg, to –1.90 with 150 mg, compared with –0.68 with placebo (P less than .001 for all vs. placebo).
The biologic also met its other primary endpoint of achieving ACR20 level of response by 24 weeks in significantly more patients than with placebo: 73.4% for 150 mg, 61.2% for 100 mg, and 50.6% for 30 mg vs. 24.7% for placebo (P less than .001).
Adverse events were reported in all treatment dose groups (42%-54% of patients in each group), and no treatment-related safety signals were observed. Only one case each of pneumonia and angioedema were considered to be related to treatment by the investigators.
The research team suggested that the blocking of GM-CSF signaling could be applicable to patients who have failed treatment with biologics that target other pathways or for people with other inflammatory or autoimmune diseases.
“This proof-of-concept study confirms that inhibition of GM-CSF activity is a promising and novel therapeutic approach for patients with RA, including those who do not adequately respond to currently available therapies,” they concluded.
The study was funded by AstraZeneca/MedImmune. Several of the authors are employees of MedImmune and several reported financial ties to other pharmaceutical companies.
The novel biologic mavrilimumab that targets the GM-CSF pathway has shown therapeutic potential in the treatment of rheumatoid arthritis in a proof-of-concept trial, particularly in patients who have failed to respond to biologics that target other pathways.
Writing in the Annals of the Rheumatic Diseases, researchers led by Gerd R. Burmester, MD, director and professor of medicine in the department of rheumatology and clinical immunology at Charité University Hospital and the Free University and Humboldt University of Berlin, noted that despite the success of the currently available biologics to treat rheumatoid arthritis (RA), a considerable number of patients do not achieve long-term responses (Ann Rheum Dis. 2017 Feb 17. doi: 10.1136/annrheumdis-2016-210624).
Mavrilimumab is a fully human monoclonal antibody that blocks GM-CSFR and is the first biologic of its kind to target the GM-CSF pathway, they noted.
The multicenter, phase IIb, randomized trial EARTH EXPLORER 1 involved 305 patients with moderate to severe RA who were randomized in a ratio of 1:1:1:1 to subcutaneous mavrilimumab 150 mg, 100 mg, 30 mg, or placebo every other week plus methotrexate for 24 weeks.
The results showed that the GM-CSFR blocker met one of its primary endpoints by significantly reducing the 28-joint Disease Activity Score based on C-reactive protein (DAS28–CRP) from baseline to week 12 when compared with placebo. The amount of reduction increased with the dose, from –1.37 with 30 mg, to –1.64 with 100 mg, to –1.90 with 150 mg, compared with –0.68 with placebo (P less than .001 for all vs. placebo).
The biologic also met its other primary endpoint of achieving ACR20 level of response by 24 weeks in significantly more patients than with placebo: 73.4% for 150 mg, 61.2% for 100 mg, and 50.6% for 30 mg vs. 24.7% for placebo (P less than .001).
Adverse events were reported in all treatment dose groups (42%-54% of patients in each group), and no treatment-related safety signals were observed. Only one case each of pneumonia and angioedema were considered to be related to treatment by the investigators.
The research team suggested that the blocking of GM-CSF signaling could be applicable to patients who have failed treatment with biologics that target other pathways or for people with other inflammatory or autoimmune diseases.
“This proof-of-concept study confirms that inhibition of GM-CSF activity is a promising and novel therapeutic approach for patients with RA, including those who do not adequately respond to currently available therapies,” they concluded.
The study was funded by AstraZeneca/MedImmune. Several of the authors are employees of MedImmune and several reported financial ties to other pharmaceutical companies.
The novel biologic mavrilimumab that targets the GM-CSF pathway has shown therapeutic potential in the treatment of rheumatoid arthritis in a proof-of-concept trial, particularly in patients who have failed to respond to biologics that target other pathways.
Writing in the Annals of the Rheumatic Diseases, researchers led by Gerd R. Burmester, MD, director and professor of medicine in the department of rheumatology and clinical immunology at Charité University Hospital and the Free University and Humboldt University of Berlin, noted that despite the success of the currently available biologics to treat rheumatoid arthritis (RA), a considerable number of patients do not achieve long-term responses (Ann Rheum Dis. 2017 Feb 17. doi: 10.1136/annrheumdis-2016-210624).
Mavrilimumab is a fully human monoclonal antibody that blocks GM-CSFR and is the first biologic of its kind to target the GM-CSF pathway, they noted.
The multicenter, phase IIb, randomized trial EARTH EXPLORER 1 involved 305 patients with moderate to severe RA who were randomized in a ratio of 1:1:1:1 to subcutaneous mavrilimumab 150 mg, 100 mg, 30 mg, or placebo every other week plus methotrexate for 24 weeks.
The results showed that the GM-CSFR blocker met one of its primary endpoints by significantly reducing the 28-joint Disease Activity Score based on C-reactive protein (DAS28–CRP) from baseline to week 12 when compared with placebo. The amount of reduction increased with the dose, from –1.37 with 30 mg, to –1.64 with 100 mg, to –1.90 with 150 mg, compared with –0.68 with placebo (P less than .001 for all vs. placebo).
The biologic also met its other primary endpoint of achieving ACR20 level of response by 24 weeks in significantly more patients than with placebo: 73.4% for 150 mg, 61.2% for 100 mg, and 50.6% for 30 mg vs. 24.7% for placebo (P less than .001).
Adverse events were reported in all treatment dose groups (42%-54% of patients in each group), and no treatment-related safety signals were observed. Only one case each of pneumonia and angioedema were considered to be related to treatment by the investigators.
The research team suggested that the blocking of GM-CSF signaling could be applicable to patients who have failed treatment with biologics that target other pathways or for people with other inflammatory or autoimmune diseases.
“This proof-of-concept study confirms that inhibition of GM-CSF activity is a promising and novel therapeutic approach for patients with RA, including those who do not adequately respond to currently available therapies,” they concluded.
The study was funded by AstraZeneca/MedImmune. Several of the authors are employees of MedImmune and several reported financial ties to other pharmaceutical companies.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Mavrilimumab significantly reduced DAS28–CRP scores from baseline to week 12 when compared with placebo, and the mount of reduction increased with the dose, from –1.37 with 30 mg, to –1.64 with 100 mg, to –1.90 with 150 mg, compared with –0.68 with placebo (P less than .001 for all vs. placebo).
Data source: A multicenter, randomized, double-blind, placebo-controlled, phase IIb trial of 305 RA patients with moderate to severe RA.
Disclosures: The study was funded by AstraZeneca/MedImmune. Several of the authors are employees of MedImmune and several reported financial ties to other pharmaceutical companies.
Hydroxychloroquine dosing guidelines have little impact in clinical practice
A substantial number of rheumatology patients are receiving excess starting and maintenance doses of hydroxychloroquine despite the existence of dosing guidelines, a group of ophthalmologists has reported.
The report raises some concerns because hydroxychloroquine has well-established ocular side effects and toxicities that makes screening by a ophthalmologist necessary for all patients on long-term therapy.
Rebekah A. Braslow, MD, and her colleagues in the division of ophthalmology at NorthShore University HealthSystem in Illinois conducted a retrospective review of the records of 554 rheumatology patients who were prescribed hydroxychloroquine during 2009-2016 and seen by a NorthShore ophthalmologist. They found that about half of the patients were on excess initial doses of the disease-modifying antirheumatic drug, according to retinal toxicity guidelines published by the American Academy of Ophthalmology (AAO) in 2011. There was no difference in the percentage of patients on an excess starting dose before the 2011 guidelines were published (54% of 92 patients) or after (49% of 462). The maintenance dose 1 year after beginning treatment was the same as the starting dose in 84% of patients, with reductions in 7% and increases in 9% (Ophthalmology. 2017 Jan 30. doi: 10.1016/j.ophtha.2016.12.021).
The AAO revised the guidelines in 2016 to define excess doses of hydroxychloroquine as greater than 5.0 mg/kg of actual body weight (Ophthalmology. 2016;123:1386-94). Based on these new guidelines, the investigators found that 56% of 527 patients who were currently receiving hydroxychloroquine were taking excess doses, and 43% of the 527 patients were still receiving doses that are more than 50 mg in excess of the calculated target dose that is recommended by the guidelines.
“The published ophthalmology screening guidelines have had no appreciable impact on clinical practice, highlighting a persistent deficiency in patient care and a significant medico-legal risk,” they concluded.
“Our findings are particularly concerning given that choosing a proper starting dose is the single safest, simplest, and most cost-effective measure available,” they wrote.
According to the authors, there were several reasons for the widespread inaccurate dosing. Firstly, the guidelines were published in ophthalmology literature and were therefore unlikely to be seen by rheumatologists. Secondly, the formulation of the drug, currently available only in 200-mg tablet form, made it difficult to adjust doses according to a patient’s weight.
This particular issue could be addressed if the drug manufacturers expanded formulation options, or by alternating daily dosing regimens or involving compound pharmacies, they suggested.
System-wide education and prompts via electronic medical records would also go some way toward ensuring that patients are prescribed the correct dose, they added.
The study was supported by intramural research funds within the division of ophthalmology in NorthShore University Health System.
A substantial number of rheumatology patients are receiving excess starting and maintenance doses of hydroxychloroquine despite the existence of dosing guidelines, a group of ophthalmologists has reported.
The report raises some concerns because hydroxychloroquine has well-established ocular side effects and toxicities that makes screening by a ophthalmologist necessary for all patients on long-term therapy.
Rebekah A. Braslow, MD, and her colleagues in the division of ophthalmology at NorthShore University HealthSystem in Illinois conducted a retrospective review of the records of 554 rheumatology patients who were prescribed hydroxychloroquine during 2009-2016 and seen by a NorthShore ophthalmologist. They found that about half of the patients were on excess initial doses of the disease-modifying antirheumatic drug, according to retinal toxicity guidelines published by the American Academy of Ophthalmology (AAO) in 2011. There was no difference in the percentage of patients on an excess starting dose before the 2011 guidelines were published (54% of 92 patients) or after (49% of 462). The maintenance dose 1 year after beginning treatment was the same as the starting dose in 84% of patients, with reductions in 7% and increases in 9% (Ophthalmology. 2017 Jan 30. doi: 10.1016/j.ophtha.2016.12.021).
The AAO revised the guidelines in 2016 to define excess doses of hydroxychloroquine as greater than 5.0 mg/kg of actual body weight (Ophthalmology. 2016;123:1386-94). Based on these new guidelines, the investigators found that 56% of 527 patients who were currently receiving hydroxychloroquine were taking excess doses, and 43% of the 527 patients were still receiving doses that are more than 50 mg in excess of the calculated target dose that is recommended by the guidelines.
“The published ophthalmology screening guidelines have had no appreciable impact on clinical practice, highlighting a persistent deficiency in patient care and a significant medico-legal risk,” they concluded.
“Our findings are particularly concerning given that choosing a proper starting dose is the single safest, simplest, and most cost-effective measure available,” they wrote.
According to the authors, there were several reasons for the widespread inaccurate dosing. Firstly, the guidelines were published in ophthalmology literature and were therefore unlikely to be seen by rheumatologists. Secondly, the formulation of the drug, currently available only in 200-mg tablet form, made it difficult to adjust doses according to a patient’s weight.
This particular issue could be addressed if the drug manufacturers expanded formulation options, or by alternating daily dosing regimens or involving compound pharmacies, they suggested.
System-wide education and prompts via electronic medical records would also go some way toward ensuring that patients are prescribed the correct dose, they added.
The study was supported by intramural research funds within the division of ophthalmology in NorthShore University Health System.
A substantial number of rheumatology patients are receiving excess starting and maintenance doses of hydroxychloroquine despite the existence of dosing guidelines, a group of ophthalmologists has reported.
The report raises some concerns because hydroxychloroquine has well-established ocular side effects and toxicities that makes screening by a ophthalmologist necessary for all patients on long-term therapy.
Rebekah A. Braslow, MD, and her colleagues in the division of ophthalmology at NorthShore University HealthSystem in Illinois conducted a retrospective review of the records of 554 rheumatology patients who were prescribed hydroxychloroquine during 2009-2016 and seen by a NorthShore ophthalmologist. They found that about half of the patients were on excess initial doses of the disease-modifying antirheumatic drug, according to retinal toxicity guidelines published by the American Academy of Ophthalmology (AAO) in 2011. There was no difference in the percentage of patients on an excess starting dose before the 2011 guidelines were published (54% of 92 patients) or after (49% of 462). The maintenance dose 1 year after beginning treatment was the same as the starting dose in 84% of patients, with reductions in 7% and increases in 9% (Ophthalmology. 2017 Jan 30. doi: 10.1016/j.ophtha.2016.12.021).
The AAO revised the guidelines in 2016 to define excess doses of hydroxychloroquine as greater than 5.0 mg/kg of actual body weight (Ophthalmology. 2016;123:1386-94). Based on these new guidelines, the investigators found that 56% of 527 patients who were currently receiving hydroxychloroquine were taking excess doses, and 43% of the 527 patients were still receiving doses that are more than 50 mg in excess of the calculated target dose that is recommended by the guidelines.
“The published ophthalmology screening guidelines have had no appreciable impact on clinical practice, highlighting a persistent deficiency in patient care and a significant medico-legal risk,” they concluded.
“Our findings are particularly concerning given that choosing a proper starting dose is the single safest, simplest, and most cost-effective measure available,” they wrote.
According to the authors, there were several reasons for the widespread inaccurate dosing. Firstly, the guidelines were published in ophthalmology literature and were therefore unlikely to be seen by rheumatologists. Secondly, the formulation of the drug, currently available only in 200-mg tablet form, made it difficult to adjust doses according to a patient’s weight.
This particular issue could be addressed if the drug manufacturers expanded formulation options, or by alternating daily dosing regimens or involving compound pharmacies, they suggested.
System-wide education and prompts via electronic medical records would also go some way toward ensuring that patients are prescribed the correct dose, they added.
The study was supported by intramural research funds within the division of ophthalmology in NorthShore University Health System.
FROM OPHTHALMOLOGY
Key clinical point:
Major finding: Nearly half of the patients seen by rheumatologist in a health system were prescribed excess initial doses of hydroxychloroquine and just over half of the patients (56%) were taking excess maintenance doses, according to 2016 dosing guidelines.
Data source: A retrospective review of the electronic medical records of 554 rheumatology patients.
Disclosures: The study was supported by intramural research funds within the division of ophthalmology in NorthShore University HealthSystem.
Adolescent depression climbs, but is not matched by treatment
Major depressive episodes among adolescents are on the rise but there hasn’t been a corresponding rise in treatment levels, suggesting many teens are left untreated.
The 12-month prevalence of major depressive episodes (MDE) in adolescents aged 12-17 years rose to 11.3% in 2014, from 8.7% in 2005, according to data from the National Surveys on Drug Use and Health. This corresponded to a 37% increase in odds over the time period studied (odds ratio, 1.37; 95% confidence interval, 1.27-1.48; P less than .001).
For young adults aged 18-25 years, the change was more modest, from 8.8% in 2005 to 9.6% in 2014 (OR, 1.13; 95%, CI, 1.05-1.22; P = .001), the researchers noted.
The trend of rising depression rates was limited to those in the 12-20 year age range and was more prominent among non-Hispanic whites and adolescent girls.
The researchers found no link between the increasing trend in depression and factors typically associated with adverse mental health outcomes, such as substance abuse, single parent homes, or income.
Of particular concern was the finding that the proportion of adolescents with depression who received treatment or counseling did not significantly change over the time period studied. While the use of specialty mental health providers increased in adolescents and young adults, most of the increases were limited to the years after 2011.
“In view of the growing prevalence of MDE in these age groups, stable treatment rates translate into a growing number of untreated depressed adolescents,” the researchers wrote. “These trends suggest that little progress has been made in narrowing the mental health treatment gap for adolescent depression. This lack of progress may reflect lingering reluctance on the part of providers to diagnose and treat depression in the wake of the FDA’s black box warning regarding the use of antidepressants.”
The researchers reported having no relevant financial disclosures.
Depression is a sizable and growing deadly threat to our U.S. adolescent population. The prioritization of youth depression treatment of our U.S. population health is imperative. In fact, the American Academy of Pediatrics recently updated its 2007 statement on recognizing suicide risks with a recommendation to routinely screen youth aged 11-21 for depression.
Sadly, even if this important update influences primary care providers to screen more youth, there will never be enough qualified mental health specialists to take care of the million or more adolescents per year, who, if screened and identified, will need treatment and monitoring for depression. The most recently updated Accreditation Council for Graduate Medical Education program requirements for graduate medical education in Pediatrics and Child and Adolescent Psychiatry are such that trainees in neither specialty are clearly required to gain specific skills to tackle the plague of youth depression at a population level.
Is it not time for educational requirements that reflect the urgent needs of our pediatric patients?
Anne Glowinski, MD, and Giuseppe D’Amelio are from Washington University in St. Louis. Dr. Glowinski serves on the Advisory Board of the Klingenstein Third Generation Foundation and the Accreditation Council for Graduate Medical Education Psychiatry Residency Review Committee. Mr. D’Amelio reported having no relevant financial disclosures. Their comments are adapted from an accompanying editorial (Pediatrics. 2016 Nov 14. doi: 10.1542/peds.2016-2869 ).
Depression is a sizable and growing deadly threat to our U.S. adolescent population. The prioritization of youth depression treatment of our U.S. population health is imperative. In fact, the American Academy of Pediatrics recently updated its 2007 statement on recognizing suicide risks with a recommendation to routinely screen youth aged 11-21 for depression.
Sadly, even if this important update influences primary care providers to screen more youth, there will never be enough qualified mental health specialists to take care of the million or more adolescents per year, who, if screened and identified, will need treatment and monitoring for depression. The most recently updated Accreditation Council for Graduate Medical Education program requirements for graduate medical education in Pediatrics and Child and Adolescent Psychiatry are such that trainees in neither specialty are clearly required to gain specific skills to tackle the plague of youth depression at a population level.
Is it not time for educational requirements that reflect the urgent needs of our pediatric patients?
Anne Glowinski, MD, and Giuseppe D’Amelio are from Washington University in St. Louis. Dr. Glowinski serves on the Advisory Board of the Klingenstein Third Generation Foundation and the Accreditation Council for Graduate Medical Education Psychiatry Residency Review Committee. Mr. D’Amelio reported having no relevant financial disclosures. Their comments are adapted from an accompanying editorial (Pediatrics. 2016 Nov 14. doi: 10.1542/peds.2016-2869 ).
Depression is a sizable and growing deadly threat to our U.S. adolescent population. The prioritization of youth depression treatment of our U.S. population health is imperative. In fact, the American Academy of Pediatrics recently updated its 2007 statement on recognizing suicide risks with a recommendation to routinely screen youth aged 11-21 for depression.
Sadly, even if this important update influences primary care providers to screen more youth, there will never be enough qualified mental health specialists to take care of the million or more adolescents per year, who, if screened and identified, will need treatment and monitoring for depression. The most recently updated Accreditation Council for Graduate Medical Education program requirements for graduate medical education in Pediatrics and Child and Adolescent Psychiatry are such that trainees in neither specialty are clearly required to gain specific skills to tackle the plague of youth depression at a population level.
Is it not time for educational requirements that reflect the urgent needs of our pediatric patients?
Anne Glowinski, MD, and Giuseppe D’Amelio are from Washington University in St. Louis. Dr. Glowinski serves on the Advisory Board of the Klingenstein Third Generation Foundation and the Accreditation Council for Graduate Medical Education Psychiatry Residency Review Committee. Mr. D’Amelio reported having no relevant financial disclosures. Their comments are adapted from an accompanying editorial (Pediatrics. 2016 Nov 14. doi: 10.1542/peds.2016-2869 ).
Major depressive episodes among adolescents are on the rise but there hasn’t been a corresponding rise in treatment levels, suggesting many teens are left untreated.
The 12-month prevalence of major depressive episodes (MDE) in adolescents aged 12-17 years rose to 11.3% in 2014, from 8.7% in 2005, according to data from the National Surveys on Drug Use and Health. This corresponded to a 37% increase in odds over the time period studied (odds ratio, 1.37; 95% confidence interval, 1.27-1.48; P less than .001).
For young adults aged 18-25 years, the change was more modest, from 8.8% in 2005 to 9.6% in 2014 (OR, 1.13; 95%, CI, 1.05-1.22; P = .001), the researchers noted.
The trend of rising depression rates was limited to those in the 12-20 year age range and was more prominent among non-Hispanic whites and adolescent girls.
The researchers found no link between the increasing trend in depression and factors typically associated with adverse mental health outcomes, such as substance abuse, single parent homes, or income.
Of particular concern was the finding that the proportion of adolescents with depression who received treatment or counseling did not significantly change over the time period studied. While the use of specialty mental health providers increased in adolescents and young adults, most of the increases were limited to the years after 2011.
“In view of the growing prevalence of MDE in these age groups, stable treatment rates translate into a growing number of untreated depressed adolescents,” the researchers wrote. “These trends suggest that little progress has been made in narrowing the mental health treatment gap for adolescent depression. This lack of progress may reflect lingering reluctance on the part of providers to diagnose and treat depression in the wake of the FDA’s black box warning regarding the use of antidepressants.”
The researchers reported having no relevant financial disclosures.
Major depressive episodes among adolescents are on the rise but there hasn’t been a corresponding rise in treatment levels, suggesting many teens are left untreated.
The 12-month prevalence of major depressive episodes (MDE) in adolescents aged 12-17 years rose to 11.3% in 2014, from 8.7% in 2005, according to data from the National Surveys on Drug Use and Health. This corresponded to a 37% increase in odds over the time period studied (odds ratio, 1.37; 95% confidence interval, 1.27-1.48; P less than .001).
For young adults aged 18-25 years, the change was more modest, from 8.8% in 2005 to 9.6% in 2014 (OR, 1.13; 95%, CI, 1.05-1.22; P = .001), the researchers noted.
The trend of rising depression rates was limited to those in the 12-20 year age range and was more prominent among non-Hispanic whites and adolescent girls.
The researchers found no link between the increasing trend in depression and factors typically associated with adverse mental health outcomes, such as substance abuse, single parent homes, or income.
Of particular concern was the finding that the proportion of adolescents with depression who received treatment or counseling did not significantly change over the time period studied. While the use of specialty mental health providers increased in adolescents and young adults, most of the increases were limited to the years after 2011.
“In view of the growing prevalence of MDE in these age groups, stable treatment rates translate into a growing number of untreated depressed adolescents,” the researchers wrote. “These trends suggest that little progress has been made in narrowing the mental health treatment gap for adolescent depression. This lack of progress may reflect lingering reluctance on the part of providers to diagnose and treat depression in the wake of the FDA’s black box warning regarding the use of antidepressants.”
The researchers reported having no relevant financial disclosures.
FROM PEDIATRICS
Key clinical finding: Adolescent depression is on the rise, but treatment rates have stayed the same indicating undertreatment in this population.
Main finding: The 12-month prevalence of major depressive episodes in adolescents (aged 12-17 years) was 11.3% in 2014, compared with 8.7% in 2005.
Source: Analysis of data from the National Surveys on Drug Use and Health from 2005 to 2014 involving 172,495 adolescents aged 12-17 years and 178,755 adults aged 18-25 years.
Disclosures: The researchers reported having no relevant financial disclosures.