Osteoarthritis

AMSTERDAM – A single intra-articular injection of a novel corticosteroid formulation provided substantial and persistent pain relief for at least 12 weeks in patients with knee osteoarthritis in a phase III trial that was presented at the World Congress on Osteoarthritis.

FX006 (Zilretta), given at a dose of 40 mg, significantly (P less than .05) reduced the mean daily pain intensity score from around 2 weeks onwards in the region of 3.0 to 3.5 points on a 0-10 scale compared with a reduction of around 1.5 to 2.0 points for placebo. There were also significant reductions in additional efficacy outcomes such as Western Ontario and McMaster Universities Index (WOMAC) pain and function versus placebo and a standard formulation of triamcinolone acetate (TCA).

Data from a phase IIb trial had originally been scheduled to be presented at the meeting – which is sponsored by the Osteoarthritis Research Society International – but the phase III findings had just become available, said Dr. Philip Conaghan of the University of Leeds (England). The phase II findings showed that there was a substantial and persistent pain relieving effect of FX006 versus placebo and that there was evidence of a dose response.

These data provide “proof of concept that we can develop long-acting steroids that have real potential for changing how we might manage knee OA,” said Dr. Conaghan, professor of musculoskeletal medicine and deputy director of the Leeds Musculoskeletal Biomedical Research Unit.

Intra-articular steroids have long been used to treat OA and they can be effective, albeit for a short period of time. FX006 is an investigational formulation of TCA in polylactic-co-glycolic acid microspheres that has been designed to try to extend the analgesic effects of the steroid and to reduce overall systemic exposure and thus side effects. Each microsphere is around 45 microns in diameter.

The aim of the phase IIb study was to examine the efficacy of two doses of FX006 (20 mg and 40 mg) versus placebo in patients with moderate to severe OA knee pain. The double-blind, randomized trial involved 310 patients who were followed for 24 weeks. The primary outcome was the change from baseline to week 12 in the weekly mean of the average daily pain intensity scores, compared with placebo.

There was evidence of a dose response, with the 40-mg dose of FX006 producing statistically significantly greater changes in pain scores versus placebo. Although the primary endpoint of a statistical difference at 12 weeks was not met, there were significant differences at all other time points from week 1 to 13. WOMAC pain and function scores were also significantly reduced with the 40-mg dose versus placebo.

The phase III trial involved 484 patients who were randomized to intra-articular injections of FX006 40 mg, standard TCA 40 mg, or placebo. As in the phase IIb trial patients were well matched at baseline, with a mean overall age of 62 years, a body mass index of 30 kg/m² and around two-thirds having OA in both knees.

Dr. Conaghan reported that there were “no unexpected safety signals” during the trials. A combined safety summary showed that treatment-emergent adverse events occurred in 42.2% and 50.9% of patients treated with FX006 20 mg and 40 mg, respectively, in 49.2% of placebo-treated patients, and in 56.5% of TCA-treated patients. Serious adverse event rates were 1%, 3%, 1.1%, and 2.5%, respectively, and were assessed as being unrelated to treatment. Adverse events related to the knee occurred in 14.7%, 16.6%, 14.1%, and 9.9%, and injection-related adverse events in 2%, 1.9%, 4.2%, and 1.9%, respectively.

The studies were funded by Flexion Therapeutics. Dr. Conaghan did not report his financial disclosures.

AMSTERDAM – A single intra-articular injection of a novel corticosteroid formulation provided substantial and persistent pain relief for at least 12 weeks in patients with knee osteoarthritis in a phase III trial that was presented at the World Congress on Osteoarthritis.

FX006 (Zilretta), given at a dose of 40 mg, significantly (P less than .05) reduced the mean daily pain intensity score from around 2 weeks onwards in the region of 3.0 to 3.5 points on a 0-10 scale compared with a reduction of around 1.5 to 2.0 points for placebo. There were also significant reductions in additional efficacy outcomes such as Western Ontario and McMaster Universities Index (WOMAC) pain and function versus placebo and a standard formulation of triamcinolone acetate (TCA).

Data from a phase IIb trial had originally been scheduled to be presented at the meeting – which is sponsored by the Osteoarthritis Research Society International – but the phase III findings had just become available, said Dr. Philip Conaghan of the University of Leeds (England). The phase II findings showed that there was a substantial and persistent pain relieving effect of FX006 versus placebo and that there was evidence of a dose response.

These data provide “proof of concept that we can develop long-acting steroids that have real potential for changing how we might manage knee OA,” said Dr. Conaghan, professor of musculoskeletal medicine and deputy director of the Leeds Musculoskeletal Biomedical Research Unit.

Intra-articular steroids have long been used to treat OA and they can be effective, albeit for a short period of time. FX006 is an investigational formulation of TCA in polylactic-co-glycolic acid microspheres that has been designed to try to extend the analgesic effects of the steroid and to reduce overall systemic exposure and thus side effects. Each microsphere is around 45 microns in diameter.

The aim of the phase IIb study was to examine the efficacy of two doses of FX006 (20 mg and 40 mg) versus placebo in patients with moderate to severe OA knee pain. The double-blind, randomized trial involved 310 patients who were followed for 24 weeks. The primary outcome was the change from baseline to week 12 in the weekly mean of the average daily pain intensity scores, compared with placebo.

There was evidence of a dose response, with the 40-mg dose of FX006 producing statistically significantly greater changes in pain scores versus placebo. Although the primary endpoint of a statistical difference at 12 weeks was not met, there were significant differences at all other time points from week 1 to 13. WOMAC pain and function scores were also significantly reduced with the 40-mg dose versus placebo.

The phase III trial involved 484 patients who were randomized to intra-articular injections of FX006 40 mg, standard TCA 40 mg, or placebo. As in the phase IIb trial patients were well matched at baseline, with a mean overall age of 62 years, a body mass index of 30 kg/m² and around two-thirds having OA in both knees.

Dr. Conaghan reported that there were “no unexpected safety signals” during the trials. A combined safety summary showed that treatment-emergent adverse events occurred in 42.2% and 50.9% of patients treated with FX006 20 mg and 40 mg, respectively, in 49.2% of placebo-treated patients, and in 56.5% of TCA-treated patients. Serious adverse event rates were 1%, 3%, 1.1%, and 2.5%, respectively, and were assessed as being unrelated to treatment. Adverse events related to the knee occurred in 14.7%, 16.6%, 14.1%, and 9.9%, and injection-related adverse events in 2%, 1.9%, 4.2%, and 1.9%, respectively.

The studies were funded by Flexion Therapeutics. Dr. Conaghan did not report his financial disclosures.

AMSTERDAM – A single intra-articular injection of a novel corticosteroid formulation provided substantial and persistent pain relief for at least 12 weeks in patients with knee osteoarthritis in a phase III trial that was presented at the World Congress on Osteoarthritis.

FX006 (Zilretta), given at a dose of 40 mg, significantly (P less than .05) reduced the mean daily pain intensity score from around 2 weeks onwards in the region of 3.0 to 3.5 points on a 0-10 scale compared with a reduction of around 1.5 to 2.0 points for placebo. There were also significant reductions in additional efficacy outcomes such as Western Ontario and McMaster Universities Index (WOMAC) pain and function versus placebo and a standard formulation of triamcinolone acetate (TCA).

Data from a phase IIb trial had originally been scheduled to be presented at the meeting – which is sponsored by the Osteoarthritis Research Society International – but the phase III findings had just become available, said Dr. Philip Conaghan of the University of Leeds (England). The phase II findings showed that there was a substantial and persistent pain relieving effect of FX006 versus placebo and that there was evidence of a dose response.

These data provide “proof of concept that we can develop long-acting steroids that have real potential for changing how we might manage knee OA,” said Dr. Conaghan, professor of musculoskeletal medicine and deputy director of the Leeds Musculoskeletal Biomedical Research Unit.

Intra-articular steroids have long been used to treat OA and they can be effective, albeit for a short period of time. FX006 is an investigational formulation of TCA in polylactic-co-glycolic acid microspheres that has been designed to try to extend the analgesic effects of the steroid and to reduce overall systemic exposure and thus side effects. Each microsphere is around 45 microns in diameter.

The aim of the phase IIb study was to examine the efficacy of two doses of FX006 (20 mg and 40 mg) versus placebo in patients with moderate to severe OA knee pain. The double-blind, randomized trial involved 310 patients who were followed for 24 weeks. The primary outcome was the change from baseline to week 12 in the weekly mean of the average daily pain intensity scores, compared with placebo.

There was evidence of a dose response, with the 40-mg dose of FX006 producing statistically significantly greater changes in pain scores versus placebo. Although the primary endpoint of a statistical difference at 12 weeks was not met, there were significant differences at all other time points from week 1 to 13. WOMAC pain and function scores were also significantly reduced with the 40-mg dose versus placebo.

The phase III trial involved 484 patients who were randomized to intra-articular injections of FX006 40 mg, standard TCA 40 mg, or placebo. As in the phase IIb trial patients were well matched at baseline, with a mean overall age of 62 years, a body mass index of 30 kg/m² and around two-thirds having OA in both knees.

Dr. Conaghan reported that there were “no unexpected safety signals” during the trials. A combined safety summary showed that treatment-emergent adverse events occurred in 42.2% and 50.9% of patients treated with FX006 20 mg and 40 mg, respectively, in 49.2% of placebo-treated patients, and in 56.5% of TCA-treated patients. Serious adverse event rates were 1%, 3%, 1.1%, and 2.5%, respectively, and were assessed as being unrelated to treatment. Adverse events related to the knee occurred in 14.7%, 16.6%, 14.1%, and 9.9%, and injection-related adverse events in 2%, 1.9%, 4.2%, and 1.9%, respectively.

The studies were funded by Flexion Therapeutics. Dr. Conaghan did not report his financial disclosures.

AMSTERDAM – Persistent knee pain is an important predictor of structural joint damage and could potentially be used to predict knee osteoarthritis (OA) earlier, according to Dutch research reported at the World Congress on Osteoarthritis.

The analysis found that women participating in the Rotterdam Study who had knee pain on most days of the preceding month were more than four times more likely to develop knee OA within 5 years on MRI (odds ratio, 4.53) than were those without frequent knee pain.

©decade3d/Thinkstock.com

Other signs and symptoms predictive of later OA on MRI included a history of knee injury (OR, 2.52), pain on palpation (OR, 2.30) or during activity (OR, 2.13), the feeling of the knee giving way (OR, 2.13), joint line tenderness (OR, 2.04), crepitus (or grating sounds or sensations; OR, 1.85), and Heberden’s nodes (OR, 1.67).

“Signs and symptoms can predict structural knee OA in 5 years in women without knee OA at baseline,” said the presenting study author Dieuwke Schiphof, Ph.D., a postdoctoral researcher at Erasmus University Medical Center in Rotterdam, at the meeting sponsored by the Osteoarthritis Research Society International.

“Knee pain on most days of the last month is an important predictive symptom for all structural OA definitions,” she said, adding that crepitus was an important sign of patellofemoral OA, and the feeling of giving way and joint line tenderness were important signs for tibiofemoral OA.

The aim of their study was to try to determine the value of previously identified clinical signs and symptoms for determining the onset of structural knee OA. Around 600 women aged 45-60 years without OA at baseline were included from the population-based cohort Rotterdam study. Participants had completed a standard questionnaire and had physical, radiographic, and MRI examination of both knees at baseline and at a mean follow-up of 5 years later.

The mean age of women was 59.5 years and 33 of 1,137 knees had isolated patellofemoral OA and 69 had isolated tibiofemoral OA, 111 one or the other, and 22 had radiographic knee OA.

Results showed that knee pain on most days of the last month (OR, 7.57) and crepitus (OR, 3.05) were most predictive of isolated patellofemoral OA on MRI. The prevalence of patellofemoral OA was 3% but this increased to 20% if both these signs and symptoms were present.

Knee pain on most days of the last month (OR, 4.13) was also predictive of isolated tibiofemoral OA on MRI, together with a history of knee pain (OR, 2.48), knee pain during activities (OR, 2.04), and the feeling of the knee giving way (OR, 3.15). If two or three or more signs and symptoms were present, the predictive value increased from a prevalence of 6% to 12% to 18%.

Knee pain on most days of the last month was also highly predictive of radiographic OA (OR, 7.77), as was pain at palpation (OR, 4.36), prior injury (OR, 3.64), and the feeling of the knee giving way (OR, 2.75). Again, when additional signs or symptoms were present the prevalence increased from a prevalence of 3% at follow-up to 4% with one, 8% with two, and up to 14% for three or more.

These signs and symptoms could potentially be used to help identify patients that may benefit from preventive treatment for knee OA, the researchers believe.

The study was funded by The Netherlands Organisation for Health Research and Development and Reumafonds, the Dutch Arthritis Association. Dr. Schiphof had no financial disclosures.

AMSTERDAM – Persistent knee pain is an important predictor of structural joint damage and could potentially be used to predict knee osteoarthritis (OA) earlier, according to Dutch research reported at the World Congress on Osteoarthritis.

The analysis found that women participating in the Rotterdam Study who had knee pain on most days of the preceding month were more than four times more likely to develop knee OA within 5 years on MRI (odds ratio, 4.53) than were those without frequent knee pain.

©decade3d/Thinkstock.com

Other signs and symptoms predictive of later OA on MRI included a history of knee injury (OR, 2.52), pain on palpation (OR, 2.30) or during activity (OR, 2.13), the feeling of the knee giving way (OR, 2.13), joint line tenderness (OR, 2.04), crepitus (or grating sounds or sensations; OR, 1.85), and Heberden’s nodes (OR, 1.67).

“Signs and symptoms can predict structural knee OA in 5 years in women without knee OA at baseline,” said the presenting study author Dieuwke Schiphof, Ph.D., a postdoctoral researcher at Erasmus University Medical Center in Rotterdam, at the meeting sponsored by the Osteoarthritis Research Society International.

“Knee pain on most days of the last month is an important predictive symptom for all structural OA definitions,” she said, adding that crepitus was an important sign of patellofemoral OA, and the feeling of giving way and joint line tenderness were important signs for tibiofemoral OA.

The aim of their study was to try to determine the value of previously identified clinical signs and symptoms for determining the onset of structural knee OA. Around 600 women aged 45-60 years without OA at baseline were included from the population-based cohort Rotterdam study. Participants had completed a standard questionnaire and had physical, radiographic, and MRI examination of both knees at baseline and at a mean follow-up of 5 years later.

The mean age of women was 59.5 years and 33 of 1,137 knees had isolated patellofemoral OA and 69 had isolated tibiofemoral OA, 111 one or the other, and 22 had radiographic knee OA.

Results showed that knee pain on most days of the last month (OR, 7.57) and crepitus (OR, 3.05) were most predictive of isolated patellofemoral OA on MRI. The prevalence of patellofemoral OA was 3% but this increased to 20% if both these signs and symptoms were present.

Knee pain on most days of the last month (OR, 4.13) was also predictive of isolated tibiofemoral OA on MRI, together with a history of knee pain (OR, 2.48), knee pain during activities (OR, 2.04), and the feeling of the knee giving way (OR, 3.15). If two or three or more signs and symptoms were present, the predictive value increased from a prevalence of 6% to 12% to 18%.

Knee pain on most days of the last month was also highly predictive of radiographic OA (OR, 7.77), as was pain at palpation (OR, 4.36), prior injury (OR, 3.64), and the feeling of the knee giving way (OR, 2.75). Again, when additional signs or symptoms were present the prevalence increased from a prevalence of 3% at follow-up to 4% with one, 8% with two, and up to 14% for three or more.

These signs and symptoms could potentially be used to help identify patients that may benefit from preventive treatment for knee OA, the researchers believe.

The study was funded by The Netherlands Organisation for Health Research and Development and Reumafonds, the Dutch Arthritis Association. Dr. Schiphof had no financial disclosures.

AMSTERDAM – Persistent knee pain is an important predictor of structural joint damage and could potentially be used to predict knee osteoarthritis (OA) earlier, according to Dutch research reported at the World Congress on Osteoarthritis.

The analysis found that women participating in the Rotterdam Study who had knee pain on most days of the preceding month were more than four times more likely to develop knee OA within 5 years on MRI (odds ratio, 4.53) than were those without frequent knee pain.

©decade3d/Thinkstock.com

Other signs and symptoms predictive of later OA on MRI included a history of knee injury (OR, 2.52), pain on palpation (OR, 2.30) or during activity (OR, 2.13), the feeling of the knee giving way (OR, 2.13), joint line tenderness (OR, 2.04), crepitus (or grating sounds or sensations; OR, 1.85), and Heberden’s nodes (OR, 1.67).

“Signs and symptoms can predict structural knee OA in 5 years in women without knee OA at baseline,” said the presenting study author Dieuwke Schiphof, Ph.D., a postdoctoral researcher at Erasmus University Medical Center in Rotterdam, at the meeting sponsored by the Osteoarthritis Research Society International.

“Knee pain on most days of the last month is an important predictive symptom for all structural OA definitions,” she said, adding that crepitus was an important sign of patellofemoral OA, and the feeling of giving way and joint line tenderness were important signs for tibiofemoral OA.

The aim of their study was to try to determine the value of previously identified clinical signs and symptoms for determining the onset of structural knee OA. Around 600 women aged 45-60 years without OA at baseline were included from the population-based cohort Rotterdam study. Participants had completed a standard questionnaire and had physical, radiographic, and MRI examination of both knees at baseline and at a mean follow-up of 5 years later.

The mean age of women was 59.5 years and 33 of 1,137 knees had isolated patellofemoral OA and 69 had isolated tibiofemoral OA, 111 one or the other, and 22 had radiographic knee OA.

Results showed that knee pain on most days of the last month (OR, 7.57) and crepitus (OR, 3.05) were most predictive of isolated patellofemoral OA on MRI. The prevalence of patellofemoral OA was 3% but this increased to 20% if both these signs and symptoms were present.

Knee pain on most days of the last month (OR, 4.13) was also predictive of isolated tibiofemoral OA on MRI, together with a history of knee pain (OR, 2.48), knee pain during activities (OR, 2.04), and the feeling of the knee giving way (OR, 3.15). If two or three or more signs and symptoms were present, the predictive value increased from a prevalence of 6% to 12% to 18%.

Knee pain on most days of the last month was also highly predictive of radiographic OA (OR, 7.77), as was pain at palpation (OR, 4.36), prior injury (OR, 3.64), and the feeling of the knee giving way (OR, 2.75). Again, when additional signs or symptoms were present the prevalence increased from a prevalence of 3% at follow-up to 4% with one, 8% with two, and up to 14% for three or more.

These signs and symptoms could potentially be used to help identify patients that may benefit from preventive treatment for knee OA, the researchers believe.

The study was funded by The Netherlands Organisation for Health Research and Development and Reumafonds, the Dutch Arthritis Association. Dr. Schiphof had no financial disclosures.

AMSTERDAM – Patients with milder knee osteoarthritis symptoms or better quality of life before undergoing total knee replacement surgery gained less benefit from the surgery than did those who had more severe symptoms in two separate analyses of British and U.S. patients.

Additional evidence from total knee replacements (TKRs) performed on U.S. participants of the Osteoarthritis Initiative also suggest that as the use of TKR has increased to include less symptomatic patients, the overall cost-effectiveness of the procedure has declined.

©pixologicstudio/ thinkstockphotos.com

“Knee replacements are one of those interventions that are known to be very effective and very cost-effective,” Rafael Pinedo-Villanueva, Ph.D., of the University of Oxford (England) said during his presentation of National Health Service data from England at the World Congress on Osteoarthritis. Indeed, knee replacements are associated with significant improvements in pain, function, and quality of life, he said, but that is if you look at the mean values.

As the deciles for baseline knee pain and function decrease in severity, there are diminishing mean improvements and an increasing proportion of patients who do worse after the operation, he reported. Up to 17% of patients had unchanged or improved knee pain scores and up to 27% had lower quality of life scores. If minimally important differences were considered, these percentages rose to 40% and 48% of patients being worse off, respectively.

“The significant improvements seem to be overshadowing what happens to those patients who are doing worse,” Dr. Pinedo-Villanueva suggested. “So essentially cost-effectiveness is being driven by the magnitude of the change in those who do improve, and we don’t really see much about what is happening to those who are doing worse.”

Of over 215,000 records of knee replacement collected from all patients undergoing TKR in England during 2008-2012, Dr. Pinedo-Villanueva and his study coauthors found 117,844 had data on pre- and post-operative knee pain assessed using the Oxford Knee Score (OKS) and quality of life measured with the EQ-5D instrument. The majority of replacements were in women (55%) and almost three quarters of patients had one or no comorbidities. Overall, the mean change in OKS was 15 points, improving from 19 to 34 (the higher the score the lesser the knee pain). EQ-5D scores also improved by a mean difference of 0.30 (from 0.41 to 0.70 where 1.0 is perfect health). Although the vast majority of patients had improved OKS and EQ-5D scores after surgery, unchanged or decreased scores were seen in 8% and 22% of patients, respectively.

“As we breakdown these data by deciles of baseline pain and function we see clearly that those starting at the lower decile improved the most, and that’s to be expected; they’ve a lot more to improve than the ones that came into the operation at the higher decile,” Dr. Pinedo-Villanueva said at the Congress, sponsored by the Osteoarthritis Research Society International. But there were patients who fared worse at every decile, he noted.

Dr. Pinedo-Villanueva concluded that outcome prediction models were needed to try to reduce the number of patients who are apparently worse off after knee replacement and improve the efficiency of resource allocation.

The value of TKR in a contemporary U.S. population was the focus of a separate presentation by Dr. Bart Ferket of Mount Sinai Hospital in New York. Dr. Ferket reported the results of a study looking at the impact of TKR on patients’ quality of life, lifetime costs, and quality-adjusted life years (QALYs) while varying the use of TKR by patients’ functional status at baseline.

“In the United States, the rate at which total knee replacement is performed has doubled in the last two decades,” Dr. Ferket observed. This “disproportionate” increase has been attributed to expanding the eligibility criteria to include less symptomatic patients.

Using data collected over an 8-year period on 1,327 participants from the Osteoarthritis Initiative, Dr. Ferket and his associates at Mount Sinai and Erasmus University Medical Center in Rotterdam (The Netherlands) discovered that the increased uptake of TKR might have affected the likely benefit and reduced the overall cost-effectiveness of the procedure.

At baseline, 17% of the participants, who all had knee osteoarthritis, had had a prior knee replacement.

Quality of life measured on the physical component scores (PCS) of the 12-item Short Form (SF-12) were generally improved after TKR but decreased in those who did not have a knee replaced. The effect on the mental component of the SF-12 was less clear, with possibly a decrease seen in some patients. Changes on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Knee injury and Osteoarthritis Outcome Score (KOOS) showed a considerable benefit for knee replacement and there was a general decrease in pain medication over time in those who had surgery. The overall effect was more pronounced if patients with greater baseline symptoms were considered.

Cost-effectiveness modeling showed that reserving TKR for more seriously affected patients may make it more economically attractive. The QALYs gained from TKR was about 11 but as the number of QALYs increased, so did the relative lifetime cost, with increasing incremental cost-effectiveness ratios (ICERs) as SF-12 PCS rose. ICERs were around $143,000, $160,000, $217,000, $385,000, and $1,175,000 considering patients with SF-12 PCS of less than 30, 35, 40, 45, and 50, respectively.

“The more lenient the eligibility criteria are, the higher the effectiveness, but also the higher the costs,” Dr. Ferket said. “The most cost-effective scenarios are actually more restrictive that what is currently seen in current practice in the U.S.”

Dr. Pinedo-Villanueva and Dr. Ferket reported having no financial disclosures.

AMSTERDAM – Patients with milder knee osteoarthritis symptoms or better quality of life before undergoing total knee replacement surgery gained less benefit from the surgery than did those who had more severe symptoms in two separate analyses of British and U.S. patients.

Additional evidence from total knee replacements (TKRs) performed on U.S. participants of the Osteoarthritis Initiative also suggest that as the use of TKR has increased to include less symptomatic patients, the overall cost-effectiveness of the procedure has declined.

©pixologicstudio/ thinkstockphotos.com

“Knee replacements are one of those interventions that are known to be very effective and very cost-effective,” Rafael Pinedo-Villanueva, Ph.D., of the University of Oxford (England) said during his presentation of National Health Service data from England at the World Congress on Osteoarthritis. Indeed, knee replacements are associated with significant improvements in pain, function, and quality of life, he said, but that is if you look at the mean values.

As the deciles for baseline knee pain and function decrease in severity, there are diminishing mean improvements and an increasing proportion of patients who do worse after the operation, he reported. Up to 17% of patients had unchanged or improved knee pain scores and up to 27% had lower quality of life scores. If minimally important differences were considered, these percentages rose to 40% and 48% of patients being worse off, respectively.

“The significant improvements seem to be overshadowing what happens to those patients who are doing worse,” Dr. Pinedo-Villanueva suggested. “So essentially cost-effectiveness is being driven by the magnitude of the change in those who do improve, and we don’t really see much about what is happening to those who are doing worse.”

Of over 215,000 records of knee replacement collected from all patients undergoing TKR in England during 2008-2012, Dr. Pinedo-Villanueva and his study coauthors found 117,844 had data on pre- and post-operative knee pain assessed using the Oxford Knee Score (OKS) and quality of life measured with the EQ-5D instrument. The majority of replacements were in women (55%) and almost three quarters of patients had one or no comorbidities. Overall, the mean change in OKS was 15 points, improving from 19 to 34 (the higher the score the lesser the knee pain). EQ-5D scores also improved by a mean difference of 0.30 (from 0.41 to 0.70 where 1.0 is perfect health). Although the vast majority of patients had improved OKS and EQ-5D scores after surgery, unchanged or decreased scores were seen in 8% and 22% of patients, respectively.

“As we breakdown these data by deciles of baseline pain and function we see clearly that those starting at the lower decile improved the most, and that’s to be expected; they’ve a lot more to improve than the ones that came into the operation at the higher decile,” Dr. Pinedo-Villanueva said at the Congress, sponsored by the Osteoarthritis Research Society International. But there were patients who fared worse at every decile, he noted.

Dr. Pinedo-Villanueva concluded that outcome prediction models were needed to try to reduce the number of patients who are apparently worse off after knee replacement and improve the efficiency of resource allocation.

The value of TKR in a contemporary U.S. population was the focus of a separate presentation by Dr. Bart Ferket of Mount Sinai Hospital in New York. Dr. Ferket reported the results of a study looking at the impact of TKR on patients’ quality of life, lifetime costs, and quality-adjusted life years (QALYs) while varying the use of TKR by patients’ functional status at baseline.

“In the United States, the rate at which total knee replacement is performed has doubled in the last two decades,” Dr. Ferket observed. This “disproportionate” increase has been attributed to expanding the eligibility criteria to include less symptomatic patients.

Using data collected over an 8-year period on 1,327 participants from the Osteoarthritis Initiative, Dr. Ferket and his associates at Mount Sinai and Erasmus University Medical Center in Rotterdam (The Netherlands) discovered that the increased uptake of TKR might have affected the likely benefit and reduced the overall cost-effectiveness of the procedure.

At baseline, 17% of the participants, who all had knee osteoarthritis, had had a prior knee replacement.

Quality of life measured on the physical component scores (PCS) of the 12-item Short Form (SF-12) were generally improved after TKR but decreased in those who did not have a knee replaced. The effect on the mental component of the SF-12 was less clear, with possibly a decrease seen in some patients. Changes on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Knee injury and Osteoarthritis Outcome Score (KOOS) showed a considerable benefit for knee replacement and there was a general decrease in pain medication over time in those who had surgery. The overall effect was more pronounced if patients with greater baseline symptoms were considered.

Cost-effectiveness modeling showed that reserving TKR for more seriously affected patients may make it more economically attractive. The QALYs gained from TKR was about 11 but as the number of QALYs increased, so did the relative lifetime cost, with increasing incremental cost-effectiveness ratios (ICERs) as SF-12 PCS rose. ICERs were around $143,000, $160,000, $217,000, $385,000, and $1,175,000 considering patients with SF-12 PCS of less than 30, 35, 40, 45, and 50, respectively.

“The more lenient the eligibility criteria are, the higher the effectiveness, but also the higher the costs,” Dr. Ferket said. “The most cost-effective scenarios are actually more restrictive that what is currently seen in current practice in the U.S.”

Dr. Pinedo-Villanueva and Dr. Ferket reported having no financial disclosures.

AMSTERDAM – Patients with milder knee osteoarthritis symptoms or better quality of life before undergoing total knee replacement surgery gained less benefit from the surgery than did those who had more severe symptoms in two separate analyses of British and U.S. patients.

Additional evidence from total knee replacements (TKRs) performed on U.S. participants of the Osteoarthritis Initiative also suggest that as the use of TKR has increased to include less symptomatic patients, the overall cost-effectiveness of the procedure has declined.

©pixologicstudio/ thinkstockphotos.com

“Knee replacements are one of those interventions that are known to be very effective and very cost-effective,” Rafael Pinedo-Villanueva, Ph.D., of the University of Oxford (England) said during his presentation of National Health Service data from England at the World Congress on Osteoarthritis. Indeed, knee replacements are associated with significant improvements in pain, function, and quality of life, he said, but that is if you look at the mean values.

As the deciles for baseline knee pain and function decrease in severity, there are diminishing mean improvements and an increasing proportion of patients who do worse after the operation, he reported. Up to 17% of patients had unchanged or improved knee pain scores and up to 27% had lower quality of life scores. If minimally important differences were considered, these percentages rose to 40% and 48% of patients being worse off, respectively.

“The significant improvements seem to be overshadowing what happens to those patients who are doing worse,” Dr. Pinedo-Villanueva suggested. “So essentially cost-effectiveness is being driven by the magnitude of the change in those who do improve, and we don’t really see much about what is happening to those who are doing worse.”

Of over 215,000 records of knee replacement collected from all patients undergoing TKR in England during 2008-2012, Dr. Pinedo-Villanueva and his study coauthors found 117,844 had data on pre- and post-operative knee pain assessed using the Oxford Knee Score (OKS) and quality of life measured with the EQ-5D instrument. The majority of replacements were in women (55%) and almost three quarters of patients had one or no comorbidities. Overall, the mean change in OKS was 15 points, improving from 19 to 34 (the higher the score the lesser the knee pain). EQ-5D scores also improved by a mean difference of 0.30 (from 0.41 to 0.70 where 1.0 is perfect health). Although the vast majority of patients had improved OKS and EQ-5D scores after surgery, unchanged or decreased scores were seen in 8% and 22% of patients, respectively.

“As we breakdown these data by deciles of baseline pain and function we see clearly that those starting at the lower decile improved the most, and that’s to be expected; they’ve a lot more to improve than the ones that came into the operation at the higher decile,” Dr. Pinedo-Villanueva said at the Congress, sponsored by the Osteoarthritis Research Society International. But there were patients who fared worse at every decile, he noted.

Dr. Pinedo-Villanueva concluded that outcome prediction models were needed to try to reduce the number of patients who are apparently worse off after knee replacement and improve the efficiency of resource allocation.

The value of TKR in a contemporary U.S. population was the focus of a separate presentation by Dr. Bart Ferket of Mount Sinai Hospital in New York. Dr. Ferket reported the results of a study looking at the impact of TKR on patients’ quality of life, lifetime costs, and quality-adjusted life years (QALYs) while varying the use of TKR by patients’ functional status at baseline.

“In the United States, the rate at which total knee replacement is performed has doubled in the last two decades,” Dr. Ferket observed. This “disproportionate” increase has been attributed to expanding the eligibility criteria to include less symptomatic patients.

Using data collected over an 8-year period on 1,327 participants from the Osteoarthritis Initiative, Dr. Ferket and his associates at Mount Sinai and Erasmus University Medical Center in Rotterdam (The Netherlands) discovered that the increased uptake of TKR might have affected the likely benefit and reduced the overall cost-effectiveness of the procedure.

At baseline, 17% of the participants, who all had knee osteoarthritis, had had a prior knee replacement.

Quality of life measured on the physical component scores (PCS) of the 12-item Short Form (SF-12) were generally improved after TKR but decreased in those who did not have a knee replaced. The effect on the mental component of the SF-12 was less clear, with possibly a decrease seen in some patients. Changes on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Knee injury and Osteoarthritis Outcome Score (KOOS) showed a considerable benefit for knee replacement and there was a general decrease in pain medication over time in those who had surgery. The overall effect was more pronounced if patients with greater baseline symptoms were considered.

Cost-effectiveness modeling showed that reserving TKR for more seriously affected patients may make it more economically attractive. The QALYs gained from TKR was about 11 but as the number of QALYs increased, so did the relative lifetime cost, with increasing incremental cost-effectiveness ratios (ICERs) as SF-12 PCS rose. ICERs were around $143,000, $160,000, $217,000, $385,000, and $1,175,000 considering patients with SF-12 PCS of less than 30, 35, 40, 45, and 50, respectively.

“The more lenient the eligibility criteria are, the higher the effectiveness, but also the higher the costs,” Dr. Ferket said. “The most cost-effective scenarios are actually more restrictive that what is currently seen in current practice in the U.S.”

Dr. Pinedo-Villanueva and Dr. Ferket reported having no financial disclosures.

Therapeutic goals set the tone for the American College of Rheumatology National Research Agenda 2016-2020 by calling for the discovery and development of new therapies for rheumatic disease; finding predictors of response and nonresponse to, and adverse events from therapy; and improving the understanding of how therapies should be used.

Those are the top 3 out of 15 goals facilitated by the ACR’s Committee on Research, which finalized the agenda after seeking input from members of the ACR and Association of Rheumatology Health Professionals (ARHP) living in the United States, and going through several rounds of refining and prioritizing the importance of goals through the input of clinicians, researchers, patients, and stakeholders. The Committee on Research uses the agenda to “set the compass for the organization in terms of research initiatives and facilitate the ACR’s advocacy for the research goals identified.”

©Tashatuvango/Thinkstock

Dr. Alexis R. Ogdie-Beatty, who jointly led the development of the agenda for the Committee on Research along with Dr. S. Louis Bridges, said that while the goals for 2016-2020 had a great deal of overlap with those of 2011-2015, “some of the topics that came up were different. Some of the topics were more specific than in the previous agenda. We have some idea how important these issues were to rheumatologists, given that rheumatologists (and patients) rated the importance of the items. Defining new therapeutic targets and developing new therapies for rheumatic diseases was by far the most highly rated goal by rheumatologists. Next most highly rated was to advocate for increased support for rheumatology research and rheumatology investigators – this was included as a supplementary goal that supports the rest of the agenda. Other newer items were those around determining how the changing health care landscape affects rheumatology patients and clinicians. In addition, nonpharmacologic therapy, adult outcomes of pediatric disease, and optimizing patient engagement were topics that were felt to be important. I think these highlight the input of clinicians in identifying research objectives.”

The 2016-2020 agenda is the third set of goals developed by the committee since 2005, and the first to “crowdsource” the important questions to ACR and ARHP members rather than be assembled solely by the committee.

The agenda arose from a multistage process that began with a web-based survey to the ACR/ARHP membership that asked respondents to “list the five most important research questions that need to be addressed over the next 5 years in order to improve the care for patients with rheumatic disease.” A selected group of 100 individuals representing patients, clinicians (academic and community), research (all types with diverse areas/diseases of interest), allied health professionals, pediatric and adult rheumatology, men and women, all career stages, and all regions of the country, used a Delphi exercise to rate 30 statements generated from the survey on a scale from 1 (not important) to 10 (very important). They had the option to provide comments. At a Leadership Summit, stakeholders from various nonprofit foundations associated with rheumatic diseases, the National Institutes of Health, and the president of the Rheumatology Research Foundation gave comments on a draft agenda to the Committee on Research, after which the committee discussed the results and input and then solicited further 1-10 ratings and comments on preliminary agenda goals from the same group of 100 individuals as in the second phase, plus an additional 17 clinicians.

Up next in the rank-ordering after therapeutic goals were three goals about understanding:

• The etiology, pathogenesis, and genetic basis of rheumatic diseases.

• Early disease states to improve early diagnosis, develop biomarkers for early detection, and determine how earlier treatment changes outcomes.

• The immune system and autoimmunity by defining autoimmunity triggers and determining how epigenetics affect disease susceptibility and inflammation.

The 5-year plan proposed developing improved outcome measures that incorporate patient self-reports, imaging, and measures of clinical response and disease activity. The agenda also seeks to gain better understanding of how patients with rheumatic disease, rheumatologists, and rheumatology health professionals are being affected by the changing U.S. health care landscape.

The plan calls for determining the role of nonpharmacologic therapy in the management of rheumatic disease (promoting and improving adherence to physical activity, finding optimal exercise prescriptions, and determining the role of diet on disease activity), as well as evaluating the role of regenerative medicine.

The agenda spells out the need for better engagement of patients in their care as well as for understanding how comorbidities are influenced by rheumatic disease and how pain and fatigue arise in rheumatic disease.

In two separate goals, committee members listed the importance of determining adult outcomes of pediatric rheumatic diseases and the effect of aging on the development, progression, and management of rheumatic diseases.

The Committee on Research identified three supplemental goals that support the others:

• Advocating for increased support for rheumatology research and rheumatology investigators.

• Harmonizing data from existing cohorts and registries to optimize research capabilities.

• Improving patient research partner involvement in research protocols.

[email protected]

Therapeutic goals set the tone for the American College of Rheumatology National Research Agenda 2016-2020 by calling for the discovery and development of new therapies for rheumatic disease; finding predictors of response and nonresponse to, and adverse events from therapy; and improving the understanding of how therapies should be used.

Those are the top 3 out of 15 goals facilitated by the ACR’s Committee on Research, which finalized the agenda after seeking input from members of the ACR and Association of Rheumatology Health Professionals (ARHP) living in the United States, and going through several rounds of refining and prioritizing the importance of goals through the input of clinicians, researchers, patients, and stakeholders. The Committee on Research uses the agenda to “set the compass for the organization in terms of research initiatives and facilitate the ACR’s advocacy for the research goals identified.”

©Tashatuvango/Thinkstock

Dr. Alexis R. Ogdie-Beatty, who jointly led the development of the agenda for the Committee on Research along with Dr. S. Louis Bridges, said that while the goals for 2016-2020 had a great deal of overlap with those of 2011-2015, “some of the topics that came up were different. Some of the topics were more specific than in the previous agenda. We have some idea how important these issues were to rheumatologists, given that rheumatologists (and patients) rated the importance of the items. Defining new therapeutic targets and developing new therapies for rheumatic diseases was by far the most highly rated goal by rheumatologists. Next most highly rated was to advocate for increased support for rheumatology research and rheumatology investigators – this was included as a supplementary goal that supports the rest of the agenda. Other newer items were those around determining how the changing health care landscape affects rheumatology patients and clinicians. In addition, nonpharmacologic therapy, adult outcomes of pediatric disease, and optimizing patient engagement were topics that were felt to be important. I think these highlight the input of clinicians in identifying research objectives.”

The 2016-2020 agenda is the third set of goals developed by the committee since 2005, and the first to “crowdsource” the important questions to ACR and ARHP members rather than be assembled solely by the committee.

The agenda arose from a multistage process that began with a web-based survey to the ACR/ARHP membership that asked respondents to “list the five most important research questions that need to be addressed over the next 5 years in order to improve the care for patients with rheumatic disease.” A selected group of 100 individuals representing patients, clinicians (academic and community), research (all types with diverse areas/diseases of interest), allied health professionals, pediatric and adult rheumatology, men and women, all career stages, and all regions of the country, used a Delphi exercise to rate 30 statements generated from the survey on a scale from 1 (not important) to 10 (very important). They had the option to provide comments. At a Leadership Summit, stakeholders from various nonprofit foundations associated with rheumatic diseases, the National Institutes of Health, and the president of the Rheumatology Research Foundation gave comments on a draft agenda to the Committee on Research, after which the committee discussed the results and input and then solicited further 1-10 ratings and comments on preliminary agenda goals from the same group of 100 individuals as in the second phase, plus an additional 17 clinicians.

Up next in the rank-ordering after therapeutic goals were three goals about understanding:

• The etiology, pathogenesis, and genetic basis of rheumatic diseases.

• Early disease states to improve early diagnosis, develop biomarkers for early detection, and determine how earlier treatment changes outcomes.

• The immune system and autoimmunity by defining autoimmunity triggers and determining how epigenetics affect disease susceptibility and inflammation.

The 5-year plan proposed developing improved outcome measures that incorporate patient self-reports, imaging, and measures of clinical response and disease activity. The agenda also seeks to gain better understanding of how patients with rheumatic disease, rheumatologists, and rheumatology health professionals are being affected by the changing U.S. health care landscape.

The plan calls for determining the role of nonpharmacologic therapy in the management of rheumatic disease (promoting and improving adherence to physical activity, finding optimal exercise prescriptions, and determining the role of diet on disease activity), as well as evaluating the role of regenerative medicine.

The agenda spells out the need for better engagement of patients in their care as well as for understanding how comorbidities are influenced by rheumatic disease and how pain and fatigue arise in rheumatic disease.

In two separate goals, committee members listed the importance of determining adult outcomes of pediatric rheumatic diseases and the effect of aging on the development, progression, and management of rheumatic diseases.

The Committee on Research identified three supplemental goals that support the others:

• Advocating for increased support for rheumatology research and rheumatology investigators.

• Harmonizing data from existing cohorts and registries to optimize research capabilities.

• Improving patient research partner involvement in research protocols.

[email protected]

Therapeutic goals set the tone for the American College of Rheumatology National Research Agenda 2016-2020 by calling for the discovery and development of new therapies for rheumatic disease; finding predictors of response and nonresponse to, and adverse events from therapy; and improving the understanding of how therapies should be used.

Those are the top 3 out of 15 goals facilitated by the ACR’s Committee on Research, which finalized the agenda after seeking input from members of the ACR and Association of Rheumatology Health Professionals (ARHP) living in the United States, and going through several rounds of refining and prioritizing the importance of goals through the input of clinicians, researchers, patients, and stakeholders. The Committee on Research uses the agenda to “set the compass for the organization in terms of research initiatives and facilitate the ACR’s advocacy for the research goals identified.”

©Tashatuvango/Thinkstock

Dr. Alexis R. Ogdie-Beatty, who jointly led the development of the agenda for the Committee on Research along with Dr. S. Louis Bridges, said that while the goals for 2016-2020 had a great deal of overlap with those of 2011-2015, “some of the topics that came up were different. Some of the topics were more specific than in the previous agenda. We have some idea how important these issues were to rheumatologists, given that rheumatologists (and patients) rated the importance of the items. Defining new therapeutic targets and developing new therapies for rheumatic diseases was by far the most highly rated goal by rheumatologists. Next most highly rated was to advocate for increased support for rheumatology research and rheumatology investigators – this was included as a supplementary goal that supports the rest of the agenda. Other newer items were those around determining how the changing health care landscape affects rheumatology patients and clinicians. In addition, nonpharmacologic therapy, adult outcomes of pediatric disease, and optimizing patient engagement were topics that were felt to be important. I think these highlight the input of clinicians in identifying research objectives.”

The 2016-2020 agenda is the third set of goals developed by the committee since 2005, and the first to “crowdsource” the important questions to ACR and ARHP members rather than be assembled solely by the committee.

The agenda arose from a multistage process that began with a web-based survey to the ACR/ARHP membership that asked respondents to “list the five most important research questions that need to be addressed over the next 5 years in order to improve the care for patients with rheumatic disease.” A selected group of 100 individuals representing patients, clinicians (academic and community), research (all types with diverse areas/diseases of interest), allied health professionals, pediatric and adult rheumatology, men and women, all career stages, and all regions of the country, used a Delphi exercise to rate 30 statements generated from the survey on a scale from 1 (not important) to 10 (very important). They had the option to provide comments. At a Leadership Summit, stakeholders from various nonprofit foundations associated with rheumatic diseases, the National Institutes of Health, and the president of the Rheumatology Research Foundation gave comments on a draft agenda to the Committee on Research, after which the committee discussed the results and input and then solicited further 1-10 ratings and comments on preliminary agenda goals from the same group of 100 individuals as in the second phase, plus an additional 17 clinicians.

Up next in the rank-ordering after therapeutic goals were three goals about understanding:

• The etiology, pathogenesis, and genetic basis of rheumatic diseases.

• Early disease states to improve early diagnosis, develop biomarkers for early detection, and determine how earlier treatment changes outcomes.

• The immune system and autoimmunity by defining autoimmunity triggers and determining how epigenetics affect disease susceptibility and inflammation.

The 5-year plan proposed developing improved outcome measures that incorporate patient self-reports, imaging, and measures of clinical response and disease activity. The agenda also seeks to gain better understanding of how patients with rheumatic disease, rheumatologists, and rheumatology health professionals are being affected by the changing U.S. health care landscape.

The plan calls for determining the role of nonpharmacologic therapy in the management of rheumatic disease (promoting and improving adherence to physical activity, finding optimal exercise prescriptions, and determining the role of diet on disease activity), as well as evaluating the role of regenerative medicine.

The agenda spells out the need for better engagement of patients in their care as well as for understanding how comorbidities are influenced by rheumatic disease and how pain and fatigue arise in rheumatic disease.

In two separate goals, committee members listed the importance of determining adult outcomes of pediatric rheumatic diseases and the effect of aging on the development, progression, and management of rheumatic diseases.

The Committee on Research identified three supplemental goals that support the others:

• Advocating for increased support for rheumatology research and rheumatology investigators.

• Harmonizing data from existing cohorts and registries to optimize research capabilities.

• Improving patient research partner involvement in research protocols.

[email protected]

The widely used painkiller acetaminophen has little effect on osteoarthritic pain even at high doses, according to results from a new meta-analysis, while several other agents, including diclofenac, improve pain more robustly.

The study, published online March 17 in The Lancet (doi: 10.1016/S0140-6736(16)30002-2), reviewed results from 74 randomized trials enrolling nearly 60,000 patients with knee or hip osteoarthritis.

©Ingram Publishing/thinkstockphotos.com

Patients were assigned different single-agent treatment regimens, comprising various dosages of seven nonsteroidal anti-inflammatory drugs (rofecoxib, lumiracoxib, etoricoxib, diclofenac, celecoxib, naproxen, and ibuprofen) or acetaminophen; in the included trials some treatments were compared head to head, and others to placebo.

First author Bruno R. da Costa, Ph.D., of the University of Bern (Switzerland) and his colleagues found to their surprise that acetaminophen had a nearly null effect on pain symptoms at doses ranging from under 2,000 mg a day to as much as 4,000 mg.

The study’s preestablished cutoff for clinically important pain reduction was an effect size of –0.37. While the most effective regimens in the study had effect sizes approaching –0.6, compared with placebo, acetaminophen’s effect size was only –0.17 across the doses studied.

Acetaminophen “is clinically ineffective and should not be recommended for the symptomatic treatment of osteoarthritis, irrespective of the dose,” the researchers concluded.

Diclofenac, meanwhile, had one of the greatest effect sizes at the maximum dose of 150 mg per day (–0.57), and etoricoxib 60 mg and rofecoxib 25 mg were comparably effective. All three agents at these maximum daily doses had 100% probability to reach the minimum clinically important difference established in the study when used to reduce osteoarthritic pain.

By comparison, maximum daily doses of ibuprofen (2,400 mg) and naproxen (1,000 mg) had 83% and 78% probability, respectively, of achieving clinically important reductions. Treatment effects increased with dosage, but reached statistical significance only for celecoxib, diclofenac, and naproxen.

“Although our findings suggest that some NSAIDs have a clinically relevant treatment effect on osteoarthritis pain,” the investigators wrote, their benefit has to be weighed against their potential harmful effects, which include cardiovascular risk associated with diclofenac and gastrointestinal complications linked to naproxen.

“Appropriate drug selection is a major challenge in patients with osteoarthritis, who are often elderly with polypharmacy. Our study will help to put the available safety data into perspective,” they wrote.

The agents were used short-term, reflecting real-life practice, with average follow-up in the study less than 3 months. However, trials with longer-term follow-up may be needed to compare effectiveness of regimens “on a continuous fixed-dose versus NSAIDs on an as-needed basis,” the researchers acknowledged.

The Swiss National Science Foundation and the Arco Foundation of Switzerland sponsored the study. One investigator disclosed institutional research support from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and the Medicines Company, while another is currently employed by Novartis and holds shares in Cogitars.

The widely used painkiller acetaminophen has little effect on osteoarthritic pain even at high doses, according to results from a new meta-analysis, while several other agents, including diclofenac, improve pain more robustly.

The study, published online March 17 in The Lancet (doi: 10.1016/S0140-6736(16)30002-2), reviewed results from 74 randomized trials enrolling nearly 60,000 patients with knee or hip osteoarthritis.

©Ingram Publishing/thinkstockphotos.com

Patients were assigned different single-agent treatment regimens, comprising various dosages of seven nonsteroidal anti-inflammatory drugs (rofecoxib, lumiracoxib, etoricoxib, diclofenac, celecoxib, naproxen, and ibuprofen) or acetaminophen; in the included trials some treatments were compared head to head, and others to placebo.

First author Bruno R. da Costa, Ph.D., of the University of Bern (Switzerland) and his colleagues found to their surprise that acetaminophen had a nearly null effect on pain symptoms at doses ranging from under 2,000 mg a day to as much as 4,000 mg.

The study’s preestablished cutoff for clinically important pain reduction was an effect size of –0.37. While the most effective regimens in the study had effect sizes approaching –0.6, compared with placebo, acetaminophen’s effect size was only –0.17 across the doses studied.

Acetaminophen “is clinically ineffective and should not be recommended for the symptomatic treatment of osteoarthritis, irrespective of the dose,” the researchers concluded.

Diclofenac, meanwhile, had one of the greatest effect sizes at the maximum dose of 150 mg per day (–0.57), and etoricoxib 60 mg and rofecoxib 25 mg were comparably effective. All three agents at these maximum daily doses had 100% probability to reach the minimum clinically important difference established in the study when used to reduce osteoarthritic pain.

By comparison, maximum daily doses of ibuprofen (2,400 mg) and naproxen (1,000 mg) had 83% and 78% probability, respectively, of achieving clinically important reductions. Treatment effects increased with dosage, but reached statistical significance only for celecoxib, diclofenac, and naproxen.

“Although our findings suggest that some NSAIDs have a clinically relevant treatment effect on osteoarthritis pain,” the investigators wrote, their benefit has to be weighed against their potential harmful effects, which include cardiovascular risk associated with diclofenac and gastrointestinal complications linked to naproxen.

“Appropriate drug selection is a major challenge in patients with osteoarthritis, who are often elderly with polypharmacy. Our study will help to put the available safety data into perspective,” they wrote.

The agents were used short-term, reflecting real-life practice, with average follow-up in the study less than 3 months. However, trials with longer-term follow-up may be needed to compare effectiveness of regimens “on a continuous fixed-dose versus NSAIDs on an as-needed basis,” the researchers acknowledged.

The Swiss National Science Foundation and the Arco Foundation of Switzerland sponsored the study. One investigator disclosed institutional research support from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and the Medicines Company, while another is currently employed by Novartis and holds shares in Cogitars.

The widely used painkiller acetaminophen has little effect on osteoarthritic pain even at high doses, according to results from a new meta-analysis, while several other agents, including diclofenac, improve pain more robustly.

The study, published online March 17 in The Lancet (doi: 10.1016/S0140-6736(16)30002-2), reviewed results from 74 randomized trials enrolling nearly 60,000 patients with knee or hip osteoarthritis.

©Ingram Publishing/thinkstockphotos.com

Patients were assigned different single-agent treatment regimens, comprising various dosages of seven nonsteroidal anti-inflammatory drugs (rofecoxib, lumiracoxib, etoricoxib, diclofenac, celecoxib, naproxen, and ibuprofen) or acetaminophen; in the included trials some treatments were compared head to head, and others to placebo.

First author Bruno R. da Costa, Ph.D., of the University of Bern (Switzerland) and his colleagues found to their surprise that acetaminophen had a nearly null effect on pain symptoms at doses ranging from under 2,000 mg a day to as much as 4,000 mg.

The study’s preestablished cutoff for clinically important pain reduction was an effect size of –0.37. While the most effective regimens in the study had effect sizes approaching –0.6, compared with placebo, acetaminophen’s effect size was only –0.17 across the doses studied.

Acetaminophen “is clinically ineffective and should not be recommended for the symptomatic treatment of osteoarthritis, irrespective of the dose,” the researchers concluded.

Diclofenac, meanwhile, had one of the greatest effect sizes at the maximum dose of 150 mg per day (–0.57), and etoricoxib 60 mg and rofecoxib 25 mg were comparably effective. All three agents at these maximum daily doses had 100% probability to reach the minimum clinically important difference established in the study when used to reduce osteoarthritic pain.

By comparison, maximum daily doses of ibuprofen (2,400 mg) and naproxen (1,000 mg) had 83% and 78% probability, respectively, of achieving clinically important reductions. Treatment effects increased with dosage, but reached statistical significance only for celecoxib, diclofenac, and naproxen.

“Although our findings suggest that some NSAIDs have a clinically relevant treatment effect on osteoarthritis pain,” the investigators wrote, their benefit has to be weighed against their potential harmful effects, which include cardiovascular risk associated with diclofenac and gastrointestinal complications linked to naproxen.

“Appropriate drug selection is a major challenge in patients with osteoarthritis, who are often elderly with polypharmacy. Our study will help to put the available safety data into perspective,” they wrote.

The agents were used short-term, reflecting real-life practice, with average follow-up in the study less than 3 months. However, trials with longer-term follow-up may be needed to compare effectiveness of regimens “on a continuous fixed-dose versus NSAIDs on an as-needed basis,” the researchers acknowledged.

The Swiss National Science Foundation and the Arco Foundation of Switzerland sponsored the study. One investigator disclosed institutional research support from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and the Medicines Company, while another is currently employed by Novartis and holds shares in Cogitars.

MAUI, HAWAII – One of the major happenings in the field of osteoarthritis in the past year was a disturbing report of dramatically increased risk of acute MI for at least 6 months after total knee replacement, panelists agreed at the 2016 Rheumatology Winter Clinical Symposium.

“What they found borders on frightening,” according to Dr. Martin J. Bergman of Drexel University, Philadelphia, and chief of rheumatology at Taylor Hospital in Ridley Park, Pa.

Bruce Jancin/Frontline Medical News

Dr. Bergman and copanelist Dr. Orrin M. Troum of the University of Southern California in Los Angeles highlighted key developments in osteoarthritis during the past year, including two major studies on total knee replacement, the Food and Drug Administration’s updated stronger warning on the cardiac and stroke risks of NSAIDs, a randomized trial which effectively takes hydroxychloroquine (Plaquenil) off the treatment menu for hand osteoarthritis, and a reassuring report on the safety of repeated intra-articular corticosteroid injections in patients with synovitic knee osteoarthritis.

Acute MI risk after total knee replacement

British investigators utilizing the U.K. National Health Service database retrospectively identified 13,849 patients who underwent total knee replacement (TKR) and an equal number of nonsurgical controls propensity-matched for cardiovascular risk factors. These two very large groups were followed for 5 years.

During the first month after TKR, the acute MI risk was 8.75-fold greater than in the matched controls. The elevated risk gradually declined thereafter, but it remained significantly higher than in controls until 1 year after surgery. At 3 months post surgery the TKR group was at fourfold increased risk of MI, compared with controls, and at 6 months their risk was still nearly double that of controls (Arthritis Rheumatol. 2015 Oct;67[10]:2771-9).

The British investigators also found a prolonged postsurgical elevated risk of MI in a large group of patients who underwent total hip replacement, although the magnitude of the increased risk, compared with matched controls, wasn’t as large as that seen after TKR.

Dr. Troum commented that the increased risk of MI during the first year after TKR identified in this study is something physicians now need to bring up in the risk/benefit discussion with patients considering TKR.

“Also, this study underscores that it may behoove us to make sure that these presurgical patients are really well worked up by a cardiologist or their primary care physician to mitigate that coronary risk as much as possible,” he added.

Another key finding in the U.K. study was that unlike the acute MI risk, the risk of venous thromboembolism following TKR remained elevated throughout the full 5 years of follow-up.

“Once you’ve had that surgery, you are at increased risk for venous thromboembolism. I think that’s something we have to keep in mind when a patient comes in with a history of total knee replacement and a complaint of calf pain or swelling – at that point, you have to think about deep venous thrombosis,” Dr. Bergman said.

TKR – Why wait?

In a Danish trial of 100 knee osteoarthritis patients deemed eligible for TKR, participants were randomized to prompt TKR followed by a 3-month regimen of exercise, dietary weight loss, physical therapy, and pain medication or to the nonsurgical regimen alone. At 12 months of follow-up, the prompt TKR group showed significantly greater improvement in a standardized score encompassing pain, symptoms, quality of life, and activities of daily living, even though one-quarter of patients in the nonsurgical treatment group bailed and underwent TKR before 12 months was up (N Engl J Med. 2015 Oct 22;373[17]:1597-606).

“My conclusion is that once you’ve determined that a patient needs and wants a total knee replacement, the patient should probably get it. Delaying – trying other modalities in an effort to lose weight and improve function – is really not going to buy you much in the way of time,” Dr. Bergman observed.

Hydroxychloroquine for hand osteoarthritis

At the 2015 European League Against Rheumatism (EULAR) meeting in Rome, Dutch investigators presented a randomized, double-blind trial in which 196 patients with symptomatic hand osteoarthritis received 6 months of hydroxychloroquine at 400 mg/day or placebo. Unlike in mild rheumatoid arthritis or lupus, hydroxychloroquine had no beneficial effect on hand osteoarthritis pain, disability, or quality of life measures.

“Plaquenil [Hydroxychloroquine] is not a good choice for patients with osteoarthritis of the hand. I think it’s a dead therapy,” Dr. Troum declared.

FDA expands warning on NSAIDs’ cardiovascular risk

On July 9, 2015, the FDA announced updated labels for NSAIDs. The new warning states that MI and stroke risk can increase as early as in the first week of NSAID use and appear to be dose- and duration-related. The agency also warned that patients who take an NSAID after a first MI are more likely to die within 1 year.

“This really brought a lot of folks to my office,” Dr. Troum recalled.

“Absolutely, this was big stuff,” Dr. Bergman agreed. “This became a nightmare for many of us because all of a sudden patients were scared to death about taking their NSAIDs.”

Intra-articular corticosteroids for knee osteoarthritis don’t accelerate cartilage deterioration

At last fall’s American College of Rheumatology meeting in San Francisco, Jeffrey B. Driban, Ph.D., of Tufts Medical Center, Boston, presented a double-blind, randomized trial of intra-articular injections of triamcinolone hexacetonide 40 mg versus saline quarterly for 2 years in 140 patients with symptomatic knee osteoarthritis with ultrasound evidence of synovitis. Participants underwent annual evaluation of periarticular bone and cartilage changes via MRI and dual-energy x-ray absorptiometry.

After 2 years, there was no difference between the two groups in terms of pain scores, walk time, or other functional measures. The injections – eight in total over 2 years – were safe, with new-onset hypertension and hyperglycemia rates of 3% in this obese population. And most important of all, there were no major differences between the two groups in terms of quantitative or semiquantitative structural endpoints; in other words, the injections didn’t increase the rate of structural disease progression. The intra-articular steroid group showed a modestly greater rate of loss of cartilage thickness, which the investigators deemed of uncertain clinical significance.

“The structural changes were minimal,” Dr. Troum noted. “This is only a 2-year study, but I can say that I now feel more comfortable giving these injections in patients who for whatever reason can’t get surgery.”

Dr. Bergman said that many orthopedic surgeons talk up the potential risk that intra-articular steroid injections will accelerate cartilage damage. They place an arbitrary limit on the number of injections a patient can receive.

“I think this study really helps us push back and say, ‘No, I think you’re fine in getting this procedure,’” the rheumatologist commented.

Dr. Bergman and Dr. Troum reported having no financial conflicts regarding their presentation.

[email protected]

MAUI, HAWAII – One of the major happenings in the field of osteoarthritis in the past year was a disturbing report of dramatically increased risk of acute MI for at least 6 months after total knee replacement, panelists agreed at the 2016 Rheumatology Winter Clinical Symposium.

“What they found borders on frightening,” according to Dr. Martin J. Bergman of Drexel University, Philadelphia, and chief of rheumatology at Taylor Hospital in Ridley Park, Pa.

Bruce Jancin/Frontline Medical News

Dr. Bergman and copanelist Dr. Orrin M. Troum of the University of Southern California in Los Angeles highlighted key developments in osteoarthritis during the past year, including two major studies on total knee replacement, the Food and Drug Administration’s updated stronger warning on the cardiac and stroke risks of NSAIDs, a randomized trial which effectively takes hydroxychloroquine (Plaquenil) off the treatment menu for hand osteoarthritis, and a reassuring report on the safety of repeated intra-articular corticosteroid injections in patients with synovitic knee osteoarthritis.

Acute MI risk after total knee replacement

British investigators utilizing the U.K. National Health Service database retrospectively identified 13,849 patients who underwent total knee replacement (TKR) and an equal number of nonsurgical controls propensity-matched for cardiovascular risk factors. These two very large groups were followed for 5 years.

During the first month after TKR, the acute MI risk was 8.75-fold greater than in the matched controls. The elevated risk gradually declined thereafter, but it remained significantly higher than in controls until 1 year after surgery. At 3 months post surgery the TKR group was at fourfold increased risk of MI, compared with controls, and at 6 months their risk was still nearly double that of controls (Arthritis Rheumatol. 2015 Oct;67[10]:2771-9).

The British investigators also found a prolonged postsurgical elevated risk of MI in a large group of patients who underwent total hip replacement, although the magnitude of the increased risk, compared with matched controls, wasn’t as large as that seen after TKR.

Dr. Troum commented that the increased risk of MI during the first year after TKR identified in this study is something physicians now need to bring up in the risk/benefit discussion with patients considering TKR.

“Also, this study underscores that it may behoove us to make sure that these presurgical patients are really well worked up by a cardiologist or their primary care physician to mitigate that coronary risk as much as possible,” he added.

Another key finding in the U.K. study was that unlike the acute MI risk, the risk of venous thromboembolism following TKR remained elevated throughout the full 5 years of follow-up.

“Once you’ve had that surgery, you are at increased risk for venous thromboembolism. I think that’s something we have to keep in mind when a patient comes in with a history of total knee replacement and a complaint of calf pain or swelling – at that point, you have to think about deep venous thrombosis,” Dr. Bergman said.

TKR – Why wait?

In a Danish trial of 100 knee osteoarthritis patients deemed eligible for TKR, participants were randomized to prompt TKR followed by a 3-month regimen of exercise, dietary weight loss, physical therapy, and pain medication or to the nonsurgical regimen alone. At 12 months of follow-up, the prompt TKR group showed significantly greater improvement in a standardized score encompassing pain, symptoms, quality of life, and activities of daily living, even though one-quarter of patients in the nonsurgical treatment group bailed and underwent TKR before 12 months was up (N Engl J Med. 2015 Oct 22;373[17]:1597-606).

“My conclusion is that once you’ve determined that a patient needs and wants a total knee replacement, the patient should probably get it. Delaying – trying other modalities in an effort to lose weight and improve function – is really not going to buy you much in the way of time,” Dr. Bergman observed.

Hydroxychloroquine for hand osteoarthritis

At the 2015 European League Against Rheumatism (EULAR) meeting in Rome, Dutch investigators presented a randomized, double-blind trial in which 196 patients with symptomatic hand osteoarthritis received 6 months of hydroxychloroquine at 400 mg/day or placebo. Unlike in mild rheumatoid arthritis or lupus, hydroxychloroquine had no beneficial effect on hand osteoarthritis pain, disability, or quality of life measures.

“Plaquenil [Hydroxychloroquine] is not a good choice for patients with osteoarthritis of the hand. I think it’s a dead therapy,” Dr. Troum declared.

FDA expands warning on NSAIDs’ cardiovascular risk

On July 9, 2015, the FDA announced updated labels for NSAIDs. The new warning states that MI and stroke risk can increase as early as in the first week of NSAID use and appear to be dose- and duration-related. The agency also warned that patients who take an NSAID after a first MI are more likely to die within 1 year.

“This really brought a lot of folks to my office,” Dr. Troum recalled.

“Absolutely, this was big stuff,” Dr. Bergman agreed. “This became a nightmare for many of us because all of a sudden patients were scared to death about taking their NSAIDs.”

Intra-articular corticosteroids for knee osteoarthritis don’t accelerate cartilage deterioration

At last fall’s American College of Rheumatology meeting in San Francisco, Jeffrey B. Driban, Ph.D., of Tufts Medical Center, Boston, presented a double-blind, randomized trial of intra-articular injections of triamcinolone hexacetonide 40 mg versus saline quarterly for 2 years in 140 patients with symptomatic knee osteoarthritis with ultrasound evidence of synovitis. Participants underwent annual evaluation of periarticular bone and cartilage changes via MRI and dual-energy x-ray absorptiometry.

After 2 years, there was no difference between the two groups in terms of pain scores, walk time, or other functional measures. The injections – eight in total over 2 years – were safe, with new-onset hypertension and hyperglycemia rates of 3% in this obese population. And most important of all, there were no major differences between the two groups in terms of quantitative or semiquantitative structural endpoints; in other words, the injections didn’t increase the rate of structural disease progression. The intra-articular steroid group showed a modestly greater rate of loss of cartilage thickness, which the investigators deemed of uncertain clinical significance.

“The structural changes were minimal,” Dr. Troum noted. “This is only a 2-year study, but I can say that I now feel more comfortable giving these injections in patients who for whatever reason can’t get surgery.”

Dr. Bergman said that many orthopedic surgeons talk up the potential risk that intra-articular steroid injections will accelerate cartilage damage. They place an arbitrary limit on the number of injections a patient can receive.

“I think this study really helps us push back and say, ‘No, I think you’re fine in getting this procedure,’” the rheumatologist commented.

Dr. Bergman and Dr. Troum reported having no financial conflicts regarding their presentation.

[email protected]

MAUI, HAWAII – One of the major happenings in the field of osteoarthritis in the past year was a disturbing report of dramatically increased risk of acute MI for at least 6 months after total knee replacement, panelists agreed at the 2016 Rheumatology Winter Clinical Symposium.

“What they found borders on frightening,” according to Dr. Martin J. Bergman of Drexel University, Philadelphia, and chief of rheumatology at Taylor Hospital in Ridley Park, Pa.

Bruce Jancin/Frontline Medical News

Dr. Bergman and copanelist Dr. Orrin M. Troum of the University of Southern California in Los Angeles highlighted key developments in osteoarthritis during the past year, including two major studies on total knee replacement, the Food and Drug Administration’s updated stronger warning on the cardiac and stroke risks of NSAIDs, a randomized trial which effectively takes hydroxychloroquine (Plaquenil) off the treatment menu for hand osteoarthritis, and a reassuring report on the safety of repeated intra-articular corticosteroid injections in patients with synovitic knee osteoarthritis.

Acute MI risk after total knee replacement

British investigators utilizing the U.K. National Health Service database retrospectively identified 13,849 patients who underwent total knee replacement (TKR) and an equal number of nonsurgical controls propensity-matched for cardiovascular risk factors. These two very large groups were followed for 5 years.

During the first month after TKR, the acute MI risk was 8.75-fold greater than in the matched controls. The elevated risk gradually declined thereafter, but it remained significantly higher than in controls until 1 year after surgery. At 3 months post surgery the TKR group was at fourfold increased risk of MI, compared with controls, and at 6 months their risk was still nearly double that of controls (Arthritis Rheumatol. 2015 Oct;67[10]:2771-9).

The British investigators also found a prolonged postsurgical elevated risk of MI in a large group of patients who underwent total hip replacement, although the magnitude of the increased risk, compared with matched controls, wasn’t as large as that seen after TKR.

Dr. Troum commented that the increased risk of MI during the first year after TKR identified in this study is something physicians now need to bring up in the risk/benefit discussion with patients considering TKR.

“Also, this study underscores that it may behoove us to make sure that these presurgical patients are really well worked up by a cardiologist or their primary care physician to mitigate that coronary risk as much as possible,” he added.

Another key finding in the U.K. study was that unlike the acute MI risk, the risk of venous thromboembolism following TKR remained elevated throughout the full 5 years of follow-up.

“Once you’ve had that surgery, you are at increased risk for venous thromboembolism. I think that’s something we have to keep in mind when a patient comes in with a history of total knee replacement and a complaint of calf pain or swelling – at that point, you have to think about deep venous thrombosis,” Dr. Bergman said.

TKR – Why wait?

In a Danish trial of 100 knee osteoarthritis patients deemed eligible for TKR, participants were randomized to prompt TKR followed by a 3-month regimen of exercise, dietary weight loss, physical therapy, and pain medication or to the nonsurgical regimen alone. At 12 months of follow-up, the prompt TKR group showed significantly greater improvement in a standardized score encompassing pain, symptoms, quality of life, and activities of daily living, even though one-quarter of patients in the nonsurgical treatment group bailed and underwent TKR before 12 months was up (N Engl J Med. 2015 Oct 22;373[17]:1597-606).

“My conclusion is that once you’ve determined that a patient needs and wants a total knee replacement, the patient should probably get it. Delaying – trying other modalities in an effort to lose weight and improve function – is really not going to buy you much in the way of time,” Dr. Bergman observed.

Hydroxychloroquine for hand osteoarthritis

At the 2015 European League Against Rheumatism (EULAR) meeting in Rome, Dutch investigators presented a randomized, double-blind trial in which 196 patients with symptomatic hand osteoarthritis received 6 months of hydroxychloroquine at 400 mg/day or placebo. Unlike in mild rheumatoid arthritis or lupus, hydroxychloroquine had no beneficial effect on hand osteoarthritis pain, disability, or quality of life measures.

“Plaquenil [Hydroxychloroquine] is not a good choice for patients with osteoarthritis of the hand. I think it’s a dead therapy,” Dr. Troum declared.

FDA expands warning on NSAIDs’ cardiovascular risk

On July 9, 2015, the FDA announced updated labels for NSAIDs. The new warning states that MI and stroke risk can increase as early as in the first week of NSAID use and appear to be dose- and duration-related. The agency also warned that patients who take an NSAID after a first MI are more likely to die within 1 year.

“This really brought a lot of folks to my office,” Dr. Troum recalled.

“Absolutely, this was big stuff,” Dr. Bergman agreed. “This became a nightmare for many of us because all of a sudden patients were scared to death about taking their NSAIDs.”

Intra-articular corticosteroids for knee osteoarthritis don’t accelerate cartilage deterioration

At last fall’s American College of Rheumatology meeting in San Francisco, Jeffrey B. Driban, Ph.D., of Tufts Medical Center, Boston, presented a double-blind, randomized trial of intra-articular injections of triamcinolone hexacetonide 40 mg versus saline quarterly for 2 years in 140 patients with symptomatic knee osteoarthritis with ultrasound evidence of synovitis. Participants underwent annual evaluation of periarticular bone and cartilage changes via MRI and dual-energy x-ray absorptiometry.

After 2 years, there was no difference between the two groups in terms of pain scores, walk time, or other functional measures. The injections – eight in total over 2 years – were safe, with new-onset hypertension and hyperglycemia rates of 3% in this obese population. And most important of all, there were no major differences between the two groups in terms of quantitative or semiquantitative structural endpoints; in other words, the injections didn’t increase the rate of structural disease progression. The intra-articular steroid group showed a modestly greater rate of loss of cartilage thickness, which the investigators deemed of uncertain clinical significance.

“The structural changes were minimal,” Dr. Troum noted. “This is only a 2-year study, but I can say that I now feel more comfortable giving these injections in patients who for whatever reason can’t get surgery.”

Dr. Bergman said that many orthopedic surgeons talk up the potential risk that intra-articular steroid injections will accelerate cartilage damage. They place an arbitrary limit on the number of injections a patient can receive.

“I think this study really helps us push back and say, ‘No, I think you’re fine in getting this procedure,’” the rheumatologist commented.

Dr. Bergman and Dr. Troum reported having no financial conflicts regarding their presentation.

[email protected]

All adults, including pregnant and postpartum women, should be screened for depression, according to new recommendations of the U.S. Preventive Services Task Force.

The recommendation also calls for screening to be coupled with “adequate systems” to ensure diagnosis, treatment, and follow-up (JAMA. 2016 Jan 26;315[4]:380-7).

The depression screening recommendation, authored by Dr. Albert L. Siu and the other members of the USPSTF, is a level B recommendation, meaning that it has either high certainty of moderate net benefit, or moderate certainty of moderate to substantial net benefit.

The new guidance in screening for depression helps address a disorder that is “the leading cause of disability among adults in high-income countries,” said Dr. Siu and his coauthors. Lost productivity attributable to depression cost $23 billion in the United States in 2011, and $22.8 billion was spent on treatments for depression in 2009, the last year for which figures are available.

Dr. Siu, chair of geriatrics and palliative medicine at Icahn School of Medicine at Mount Sinai, New York, and his coauthors cited “convincing evidence that screening improves the accurate identification of adult patients with depression in primary care settings, including pregnant and postpartum women.”

In addition, the task force found convincing evidence that for older adults as well as the general adult population, treatment of “depression identified through screening in primary care settings with antidepressants, psychotherapy, or both decreases clinical morbidity.”

For pregnant and postpartum women with depression, Dr. Siu and his coauthors found “adequate” evidence that cognitive behavioral therapy (CBT) improves outcomes.

The recommendation does not identify optimal timing and intervals for depression screening, citing a need for more research in this area. However, “a pragmatic approach might include screening all adults who have not been screened previously and using clinical judgment in consideration of risk factors, comorbid conditions, and life events to determine if additional screening of high-risk patients is warranted,” explained Dr. Siu and his coauthors.

The new depression screening recommendation from USPSTF updates the 2009 recommendation, which recommended universal screening if “staff-assisted depression care supports” were in place, and targeted screening based on clinical judgment and patient preference if such support were unavailable.

The rationale for the current recommendation of universal screening for those 18 years and older is the “recognition that such support is now much more widely available and accepted as part of mental health care,” the task force members said.

Any potential harms of screening, said Dr. Siu and his coauthors, were minimal to nonexistent.

Overall, the USPSTF assigned a small to moderate risk to the use of medication in depression. However, the use of “second-generation” antidepressants – mostly SSRIs – was associated with some harms, including increased risk of suicidal behavior in young adults and of gastrointestinal bleeding in older adults, as well as potential fetal harms in pregnant women taking antidepressants.

Using CBT to treat depression in pregnant and postpartum women was also associated with minimal to no harm.

The USPSTF screening recommendation is aligned with the American Academy of Family Physicians’ recommendation to screen the general adult population for depression, and with the American Academy of Pediatrics’ recommendation that pediatricians screen mothers for depression at their babies’ 1-, 2-, and 4-month office visits.

Released in draft form in July 2015, the depression screening recommendation was available for public comment for a period of 4 weeks. In response to public input, the final recommendation’s implementation section clarifies and characterizes an “adequate system” of screening, and gives more resources for evidence-based depression screening and treatment.

The Agency for Healthcare Research and Quality supports the operations of the USPSTF, but the task force’s recommendations are independent of the federal government. Dr. Siu and the other task force members reported no conflicts of interest.

[email protected]

On Twitter @karioakes

All adults, including pregnant and postpartum women, should be screened for depression, according to new recommendations of the U.S. Preventive Services Task Force.

The recommendation also calls for screening to be coupled with “adequate systems” to ensure diagnosis, treatment, and follow-up (JAMA. 2016 Jan 26;315[4]:380-7).

The depression screening recommendation, authored by Dr. Albert L. Siu and the other members of the USPSTF, is a level B recommendation, meaning that it has either high certainty of moderate net benefit, or moderate certainty of moderate to substantial net benefit.

The new guidance in screening for depression helps address a disorder that is “the leading cause of disability among adults in high-income countries,” said Dr. Siu and his coauthors. Lost productivity attributable to depression cost $23 billion in the United States in 2011, and $22.8 billion was spent on treatments for depression in 2009, the last year for which figures are available.

Dr. Siu, chair of geriatrics and palliative medicine at Icahn School of Medicine at Mount Sinai, New York, and his coauthors cited “convincing evidence that screening improves the accurate identification of adult patients with depression in primary care settings, including pregnant and postpartum women.”

In addition, the task force found convincing evidence that for older adults as well as the general adult population, treatment of “depression identified through screening in primary care settings with antidepressants, psychotherapy, or both decreases clinical morbidity.”

For pregnant and postpartum women with depression, Dr. Siu and his coauthors found “adequate” evidence that cognitive behavioral therapy (CBT) improves outcomes.

The recommendation does not identify optimal timing and intervals for depression screening, citing a need for more research in this area. However, “a pragmatic approach might include screening all adults who have not been screened previously and using clinical judgment in consideration of risk factors, comorbid conditions, and life events to determine if additional screening of high-risk patients is warranted,” explained Dr. Siu and his coauthors.

The new depression screening recommendation from USPSTF updates the 2009 recommendation, which recommended universal screening if “staff-assisted depression care supports” were in place, and targeted screening based on clinical judgment and patient preference if such support were unavailable.

The rationale for the current recommendation of universal screening for those 18 years and older is the “recognition that such support is now much more widely available and accepted as part of mental health care,” the task force members said.

Any potential harms of screening, said Dr. Siu and his coauthors, were minimal to nonexistent.

Overall, the USPSTF assigned a small to moderate risk to the use of medication in depression. However, the use of “second-generation” antidepressants – mostly SSRIs – was associated with some harms, including increased risk of suicidal behavior in young adults and of gastrointestinal bleeding in older adults, as well as potential fetal harms in pregnant women taking antidepressants.

Using CBT to treat depression in pregnant and postpartum women was also associated with minimal to no harm.

The USPSTF screening recommendation is aligned with the American Academy of Family Physicians’ recommendation to screen the general adult population for depression, and with the American Academy of Pediatrics’ recommendation that pediatricians screen mothers for depression at their babies’ 1-, 2-, and 4-month office visits.

Released in draft form in July 2015, the depression screening recommendation was available for public comment for a period of 4 weeks. In response to public input, the final recommendation’s implementation section clarifies and characterizes an “adequate system” of screening, and gives more resources for evidence-based depression screening and treatment.

The Agency for Healthcare Research and Quality supports the operations of the USPSTF, but the task force’s recommendations are independent of the federal government. Dr. Siu and the other task force members reported no conflicts of interest.

[email protected]

On Twitter @karioakes

All adults, including pregnant and postpartum women, should be screened for depression, according to new recommendations of the U.S. Preventive Services Task Force.

The recommendation also calls for screening to be coupled with “adequate systems” to ensure diagnosis, treatment, and follow-up (JAMA. 2016 Jan 26;315[4]:380-7).

The depression screening recommendation, authored by Dr. Albert L. Siu and the other members of the USPSTF, is a level B recommendation, meaning that it has either high certainty of moderate net benefit, or moderate certainty of moderate to substantial net benefit.

The new guidance in screening for depression helps address a disorder that is “the leading cause of disability among adults in high-income countries,” said Dr. Siu and his coauthors. Lost productivity attributable to depression cost $23 billion in the United States in 2011, and $22.8 billion was spent on treatments for depression in 2009, the last year for which figures are available.

Dr. Siu, chair of geriatrics and palliative medicine at Icahn School of Medicine at Mount Sinai, New York, and his coauthors cited “convincing evidence that screening improves the accurate identification of adult patients with depression in primary care settings, including pregnant and postpartum women.”

In addition, the task force found convincing evidence that for older adults as well as the general adult population, treatment of “depression identified through screening in primary care settings with antidepressants, psychotherapy, or both decreases clinical morbidity.”

For pregnant and postpartum women with depression, Dr. Siu and his coauthors found “adequate” evidence that cognitive behavioral therapy (CBT) improves outcomes.

The recommendation does not identify optimal timing and intervals for depression screening, citing a need for more research in this area. However, “a pragmatic approach might include screening all adults who have not been screened previously and using clinical judgment in consideration of risk factors, comorbid conditions, and life events to determine if additional screening of high-risk patients is warranted,” explained Dr. Siu and his coauthors.

The new depression screening recommendation from USPSTF updates the 2009 recommendation, which recommended universal screening if “staff-assisted depression care supports” were in place, and targeted screening based on clinical judgment and patient preference if such support were unavailable.

The rationale for the current recommendation of universal screening for those 18 years and older is the “recognition that such support is now much more widely available and accepted as part of mental health care,” the task force members said.

Any potential harms of screening, said Dr. Siu and his coauthors, were minimal to nonexistent.

Overall, the USPSTF assigned a small to moderate risk to the use of medication in depression. However, the use of “second-generation” antidepressants – mostly SSRIs – was associated with some harms, including increased risk of suicidal behavior in young adults and of gastrointestinal bleeding in older adults, as well as potential fetal harms in pregnant women taking antidepressants.

Using CBT to treat depression in pregnant and postpartum women was also associated with minimal to no harm.

The USPSTF screening recommendation is aligned with the American Academy of Family Physicians’ recommendation to screen the general adult population for depression, and with the American Academy of Pediatrics’ recommendation that pediatricians screen mothers for depression at their babies’ 1-, 2-, and 4-month office visits.

Released in draft form in July 2015, the depression screening recommendation was available for public comment for a period of 4 weeks. In response to public input, the final recommendation’s implementation section clarifies and characterizes an “adequate system” of screening, and gives more resources for evidence-based depression screening and treatment.

The Agency for Healthcare Research and Quality supports the operations of the USPSTF, but the task force’s recommendations are independent of the federal government. Dr. Siu and the other task force members reported no conflicts of interest.

[email protected]

On Twitter @karioakes

A wearable pulsed electromagnetic fields device reduced pain intensity and improved physical functioning in patients with painful knee osteoarthritis (OA) in a double-blind, randomized trial.

The commercially available device (ActiPatch, Bioelectronics Corp.) did not improve patients’ mental health, but significantly reduced patients’ intake of NSAIDs and analgesics, compared with placebo.

“Although NSAIDs remain the gold standard for the treatment of pain in OA, there is increasing need to find conservative and alternative approaches, in order to avoid the toxicity associated with the chronic use of the analgesics, mostly in the elderly population,” wrote Dr. Gian Luca Bagnato of the University of Messina (Italy) and his colleagues (Rheumatology [Oxford]. 2015 Dec 24. doi: 10.1093/rheumatology/kev426).

courtesy BioElectronics Corporation

Pulsed electromagnetic fields (PEMF) therapy has been shown to reduce chondrocyte apoptosis and MMP-13 expression of knee cartilage and favorably affect cartilage homeostasis in animal models, but data regarding osteoarthritis (OA) pain and function in humans are mixed.

A recent systematic review found no effect in all 14 trials analyzed, but when only high-quality randomized clinical trials were included, PEMF provided significantly better pain relief at 4 and 8 weeks and better function at 8 weeks than did placebo (Rheumatology [Oxford]. 2013;52[5]:815-24).

Not only has the quality of trials varied, so has the PEMF pulse frequency and duration used in trials, “further limiting the possibility of comparing efficacy and safety,” Dr. Bagnato and associates observed.

The current study evenly randomized 60 patients with radiologic evidence of knee OA and persistent pain to wear the PEMF or a placebo device for a minimum of 12 hours, mainly at night, with the device kept in place with a wrap. The active device emits a form of non-ionizing electromagnetic radiation at a frequency of 27.12 MHz, a pulse rate of 1,000 Hz, and a burst width of 100 microsec.

Persistent pain was defined as a minimal mean score of 40 mm for global pain on the VAS (visual analog scale) and daily pain during the month prior to enrollment despite maximal tolerated doses of conventional medical therapy, including acetaminophen and/or an NSAID. The patients’ mean age was 67.7 years and mean OA duration 12 years.

The primary efficacy endpoint was reduction in pain intensity at 1 month on the VAS and WOMAC (Western Ontario and McMaster Universities Arthritis Index). The mean WOMAC total score at baseline was 132.9.

At 1 month, VAS pain scores were reduced 25.5% with the PEMF device and 3.6% with the placebo device. The standardized treatment effect size induced by PEMF therapy was –0.73 (95% confidence interval, –1.24 to –0.19), the investigators reported.

WOMAC pain subscale and total scores fell 23.4% and 18.4% with the PEMF device versus a 2.3% reduction for both scores with the placebo device. The standardized effect size was –0.61 for WOMAC pain (95% CI, –1.12 to –0.09) and –0.34 for WOMAC total score (95% CI, –0.85 to 0.17).

At 1 month, the mean Short Form-36 physical health score was significantly better in the PEMF group than in the placebo group (55.8 vs. 53.1; P = .024), while SF-36 mental health scores were nearly identical (43.8 vs. 43.6; P = .6).

Patients were allowed per protocol to take prescribed analgesic therapy as needed, but eight patients from the PEMF group stopped these medications, while one patient from the placebo group stopped medication and three started a new therapy for chronic pain. No adverse events were reported during the study.

“Given that our data are limited to a low number of participants and the long-term efficacy of the wearable device is unknown, the generalizability of the results needs to be confirmed in a larger clinical trial with a longer duration of treatment,” Dr. Bagnato and his coauthors concluded. “However, the use of a wearable PEMF therapy in knee OA can be considered as an alternative safe and effective therapy in knee OA, providing the possibility for home-based management of pain, compared with previous studies.”

[email protected]

A wearable pulsed electromagnetic fields device reduced pain intensity and improved physical functioning in patients with painful knee osteoarthritis (OA) in a double-blind, randomized trial.

The commercially available device (ActiPatch, Bioelectronics Corp.) did not improve patients’ mental health, but significantly reduced patients’ intake of NSAIDs and analgesics, compared with placebo.

“Although NSAIDs remain the gold standard for the treatment of pain in OA, there is increasing need to find conservative and alternative approaches, in order to avoid the toxicity associated with the chronic use of the analgesics, mostly in the elderly population,” wrote Dr. Gian Luca Bagnato of the University of Messina (Italy) and his colleagues (Rheumatology [Oxford]. 2015 Dec 24. doi: 10.1093/rheumatology/kev426).

courtesy BioElectronics Corporation

Pulsed electromagnetic fields (PEMF) therapy has been shown to reduce chondrocyte apoptosis and MMP-13 expression of knee cartilage and favorably affect cartilage homeostasis in animal models, but data regarding osteoarthritis (OA) pain and function in humans are mixed.

A recent systematic review found no effect in all 14 trials analyzed, but when only high-quality randomized clinical trials were included, PEMF provided significantly better pain relief at 4 and 8 weeks and better function at 8 weeks than did placebo (Rheumatology [Oxford]. 2013;52[5]:815-24).

Not only has the quality of trials varied, so has the PEMF pulse frequency and duration used in trials, “further limiting the possibility of comparing efficacy and safety,” Dr. Bagnato and associates observed.

The current study evenly randomized 60 patients with radiologic evidence of knee OA and persistent pain to wear the PEMF or a placebo device for a minimum of 12 hours, mainly at night, with the device kept in place with a wrap. The active device emits a form of non-ionizing electromagnetic radiation at a frequency of 27.12 MHz, a pulse rate of 1,000 Hz, and a burst width of 100 microsec.

Persistent pain was defined as a minimal mean score of 40 mm for global pain on the VAS (visual analog scale) and daily pain during the month prior to enrollment despite maximal tolerated doses of conventional medical therapy, including acetaminophen and/or an NSAID. The patients’ mean age was 67.7 years and mean OA duration 12 years.

The primary efficacy endpoint was reduction in pain intensity at 1 month on the VAS and WOMAC (Western Ontario and McMaster Universities Arthritis Index). The mean WOMAC total score at baseline was 132.9.

At 1 month, VAS pain scores were reduced 25.5% with the PEMF device and 3.6% with the placebo device. The standardized treatment effect size induced by PEMF therapy was –0.73 (95% confidence interval, –1.24 to –0.19), the investigators reported.

WOMAC pain subscale and total scores fell 23.4% and 18.4% with the PEMF device versus a 2.3% reduction for both scores with the placebo device. The standardized effect size was –0.61 for WOMAC pain (95% CI, –1.12 to –0.09) and –0.34 for WOMAC total score (95% CI, –0.85 to 0.17).

At 1 month, the mean Short Form-36 physical health score was significantly better in the PEMF group than in the placebo group (55.8 vs. 53.1; P = .024), while SF-36 mental health scores were nearly identical (43.8 vs. 43.6; P = .6).

Patients were allowed per protocol to take prescribed analgesic therapy as needed, but eight patients from the PEMF group stopped these medications, while one patient from the placebo group stopped medication and three started a new therapy for chronic pain. No adverse events were reported during the study.

“Given that our data are limited to a low number of participants and the long-term efficacy of the wearable device is unknown, the generalizability of the results needs to be confirmed in a larger clinical trial with a longer duration of treatment,” Dr. Bagnato and his coauthors concluded. “However, the use of a wearable PEMF therapy in knee OA can be considered as an alternative safe and effective therapy in knee OA, providing the possibility for home-based management of pain, compared with previous studies.”

[email protected]

A wearable pulsed electromagnetic fields device reduced pain intensity and improved physical functioning in patients with painful knee osteoarthritis (OA) in a double-blind, randomized trial.

The commercially available device (ActiPatch, Bioelectronics Corp.) did not improve patients’ mental health, but significantly reduced patients’ intake of NSAIDs and analgesics, compared with placebo.

“Although NSAIDs remain the gold standard for the treatment of pain in OA, there is increasing need to find conservative and alternative approaches, in order to avoid the toxicity associated with the chronic use of the analgesics, mostly in the elderly population,” wrote Dr. Gian Luca Bagnato of the University of Messina (Italy) and his colleagues (Rheumatology [Oxford]. 2015 Dec 24. doi: 10.1093/rheumatology/kev426).

courtesy BioElectronics Corporation

Pulsed electromagnetic fields (PEMF) therapy has been shown to reduce chondrocyte apoptosis and MMP-13 expression of knee cartilage and favorably affect cartilage homeostasis in animal models, but data regarding osteoarthritis (OA) pain and function in humans are mixed.

A recent systematic review found no effect in all 14 trials analyzed, but when only high-quality randomized clinical trials were included, PEMF provided significantly better pain relief at 4 and 8 weeks and better function at 8 weeks than did placebo (Rheumatology [Oxford]. 2013;52[5]:815-24).

Not only has the quality of trials varied, so has the PEMF pulse frequency and duration used in trials, “further limiting the possibility of comparing efficacy and safety,” Dr. Bagnato and associates observed.

The current study evenly randomized 60 patients with radiologic evidence of knee OA and persistent pain to wear the PEMF or a placebo device for a minimum of 12 hours, mainly at night, with the device kept in place with a wrap. The active device emits a form of non-ionizing electromagnetic radiation at a frequency of 27.12 MHz, a pulse rate of 1,000 Hz, and a burst width of 100 microsec.

Persistent pain was defined as a minimal mean score of 40 mm for global pain on the VAS (visual analog scale) and daily pain during the month prior to enrollment despite maximal tolerated doses of conventional medical therapy, including acetaminophen and/or an NSAID. The patients’ mean age was 67.7 years and mean OA duration 12 years.

The primary efficacy endpoint was reduction in pain intensity at 1 month on the VAS and WOMAC (Western Ontario and McMaster Universities Arthritis Index). The mean WOMAC total score at baseline was 132.9.

At 1 month, VAS pain scores were reduced 25.5% with the PEMF device and 3.6% with the placebo device. The standardized treatment effect size induced by PEMF therapy was –0.73 (95% confidence interval, –1.24 to –0.19), the investigators reported.

WOMAC pain subscale and total scores fell 23.4% and 18.4% with the PEMF device versus a 2.3% reduction for both scores with the placebo device. The standardized effect size was –0.61 for WOMAC pain (95% CI, –1.12 to –0.09) and –0.34 for WOMAC total score (95% CI, –0.85 to 0.17).

At 1 month, the mean Short Form-36 physical health score was significantly better in the PEMF group than in the placebo group (55.8 vs. 53.1; P = .024), while SF-36 mental health scores were nearly identical (43.8 vs. 43.6; P = .6).

Patients were allowed per protocol to take prescribed analgesic therapy as needed, but eight patients from the PEMF group stopped these medications, while one patient from the placebo group stopped medication and three started a new therapy for chronic pain. No adverse events were reported during the study.

“Given that our data are limited to a low number of participants and the long-term efficacy of the wearable device is unknown, the generalizability of the results needs to be confirmed in a larger clinical trial with a longer duration of treatment,” Dr. Bagnato and his coauthors concluded. “However, the use of a wearable PEMF therapy in knee OA can be considered as an alternative safe and effective therapy in knee OA, providing the possibility for home-based management of pain, compared with previous studies.”

[email protected]

The coming year in rheumatology brings with it a variety of trends and concerns about how rheumatologists can chart the best course for their practices and patients amid mounting fiscal and regulatory pressures.

Questions also arise as to how rheumatology can improve its attractiveness to students and residents in 2016 with the current level of effort in mentoring, outreach, and competition against higher-paying subspecialties.

There’s also high interest and expectations in the new year for studies on systemic sclerosis and microbiome research, as well as questions about what the future holds for intra-articular hyaluronic acid and over-the-counter topical nonsteroidal anti-inflammatory drugs for osteoarthritis (OA).

Rheumatology News editorial advisory board members gave their thoughts on these areas of rheumatology in 2016.

Insurance and reimbursement problems

The changing landscape in insurance plans, brought about largely by the Affordable Care Act, is having a big impact on patients and physicians, particularly in Florida, where more than 1.5 million people signed up for an ACA federal marketplace plan in 2015. Difficulty in accessing and affording care in 2016 figures to be an even greater problem, said Dr. Norman Gaylis, who is in private practice in Aventura, Fla.

In general, many policies are passing an increased burden onto patients in regard to deductibles, copayments, and costs of medications, he said. “That’s putting tremendous stress on practices. I think this is nationwide, where we’re finding that rheumatology patients are not getting access to the drugs for [several] reasons: they’ve become unaffordable, the various pharmaceutical support programs have run out of money, and the amount of work that practices are now performing in trying to get authorization for the patients far exceeds any type of revenue [it] could be generating or should be generating to cover these increased costs. So essentially there’s a reduction in reimbursement and a reduction in revenue going along at the same time.”

Dr. Gaylis noted that there is “tremendous pressure” from all sides to reduce access to rheumatology drugs, which have rising costs. For instance, the cost of a monthly supply of generic celebrex in his practice’s area is on average $120-$200, “which is almost prohibitive for many of our patients.”

“We’re finding that this year [2015] alone, 20% of patients who are on standard infusion therapy as a routine part of their management of rheumatoid arthritis have basically dropped out,” he said. “If that’s equal across the board, that means a very high number of patients are not getting optimal care.”

The trend for rheumatologists, particularly those in solo practice, to make contracts with fewer insurance companies could accelerate in 2016, Dr. Gaylis said.

Some rheumatologists are beginning to not accept insured patients with coverage from managed care companies or the lower-tier payers, and “that’s a significant trend if it starts evolving because it will create a two-tiered system in that you’ll have the more affluent patient going to one of these practices, and then you’ll have clinics where you’ll have a totally different level of care.” Whether it builds up enough to where rheumatologists begin to develop hybrid concierge practices is a fair question, he said. “It’s very difficult to conceive of a patient paying for both primary care and subspecialist concierge service. But I am starting to see signals where there may well be some integration between concierge primary care and concierge subspecialties.”

Training, mentoring more rheumatologists

Another issue going into 2016 is the lack of mentoring and assistance to medical students and residents to draw them to the subspecialty and keep them there, as well as the viability of rheumatology as an attractive subspecialty. “It’s difficult to see how we can attract medical students and residents to the specialty when the cost of their education leaves them with staggering bills to be paid. You’ve got to be extremely passionate to want to be a rheumatologist,” Dr. Gaylis said.

Dr. Elizabeth Volkmann, clinical instructor in rheumatology at the University of California, Los Angeles, agreed and said she looked forward to seeing how the future of mentoring programs in rheumatology will progress in 2016 and beyond. She noted that the American College of Rheumatology (ACR)/Childhood Arthritis and Rheumatology Research Alliance Mentoring Interest Group (AMIGO), a career-mentoring program that serves most fellows and many junior faculty in pediatric rheumatology across the United States and Canada, recently reported success in establishing mentor contact, suitability of mentor-mentee pairing, as well as benefit with respect to career development, scholarship, and work-life balance, and was especially useful to fellows, compared with junior faculty (Arthritis Care Res. 2015 Sep 28. doi: 10.1002/acr.22732).

Dr. Volkmann expressed interest in seeing how the ACR’s Choose Rheumatology! mentorship program is performing. The program seeks to pair students and residents with rheumatologist mentors who will offer advice and help to guide them. She also pointed to the European League Against Rheumatism’s working group for young rheumatologists, the Emerging EULAR Network (EMEUNET), which seeks to promote the educational, research, and mentoring needs of young clinicians and researchers in rheumatology in Europe. as a potential model for the ACR to use in the United States.

Some of the conference-based resources available to rheumatology fellows include the ACR’s 2016 State-of-the-Art Clinical Symposium, which provides a presymposium course specifically for fellows and has sessions on choosing career paths, and the Rheumatology Research Workshop, which targets rheumatologists interested in pursuing an academic research career. Fellows-in-training travel scholarships are available for both conferences.

New systemic sclerosis and microbiome research

Many new studies in systemic sclerosis will build on results obtained in earlier-phase trials or unanswered questions arising out of treatment comparison studies. “It is a very exciting time in the world of scleroderma,” said Dr. Virginia Steen, professor of medicine at Georgetown University, Washington.

At least four new trials are studying treatments for skin manifestations of systemic sclerosis, noted Dr. Steen. In patients with diffuse cutaneous systemic sclerosis, the phase II ASSET study is testing abatacept (Orencia) against placebo and another phase II study is testing riociguat (Adempas). Roche has started enrolling patients for a phase III trial of tocilizumab (Actemra) on the heels of positive findings from its phase II study. Dr. Steen and colleagues at Johns Hopkins University are also finishing up a pilot study of the effects of intravenous immunoglobulin (Privigen) on skin disease in systemic sclerosis and should have results ready for 2016.

Two additional trials will be investigating treatments for interstitial lung disease associated with systemic sclerosis: the Scleroderma Lung Study III, testing the use of mycophenolate mofetil in all patients with the addition of pirfenidone (Esbriet) or placebo, and a separate phase III study of nintedanib (Ofev) vs. placebo that just began enrolling patients.

There are also several trials of add-on therapies, including topical nitroglycerin for Raynaud’s phenomenon or riociguat for digital ulcers, and another that is testing autologous adipose–derived regenerative cells for the treatment of hand dysfunction.

In addition to these trials now underway, the expected 2016 publication of the validation of the Combined Response Index for Systemic Sclerosis will hopefully “lead to real movement forward in the treatment of systemic sclerosis,” said Dr. Daniel E. Furst, the Carl Pearson Professor of Medicine at University of California, Los Angeles.

Further examination of the Wnt signaling pathway in systemic sclerosis should also bring better insights into the disease’s pathogenesis and potential for treatment, Dr. Furst noted, as recent experimental results have shown that its activation induces fibroblast activation with subsequent myofibroblast differentiation and excessive collagen release. Small-molecule inhibitors of Wnt signaling in early clinical trials have shown promising results.

Dr. Furst and Dr. Volkmann said they also hope for studies describing better and more specific data regarding the microbiome in rheumatic disease, especially systemic sclerosis and rheumatoid arthritis, both of which have microbiome data linked with clinically meaningful outcomes (Nat Med. 2015 Aug;21[8]:895-905).

An important unanswered question, Dr. Volkmann said, is whether differences found in GI microbial composition between diseases and between different disease subtypes are clinically meaningful.

OA treatments: AAOS guidelines, OTC topical NSAIDs

The repercussions of the American Academy of Orthopaedic Surgeons 2013 clinical practice guideline’s statement on intra-articular hyaluronic acid treatment of knee OA will continue to be felt in 2016, according to Dr. Roy D. Altman, professor emeritus of medicine at University of California, Los Angeles.

The AAOS took a different stance from all other recent treatment guidelines for knee OA by stating: “Intra-articular hyaluronic acid is no longer recommended as a method of treatment for patients with symptomatic osteoarthritis of the knee.” The AAOS’s recommendation didn’t create much confusion with physicians and patients because its use continues to increase, but instead it has contributed to “a plethora of contradictory publications and increasing resistance on coverage by insurance carriers,” Dr. Altman said.

Another unresolved issue in OA treatment is “the resistance of the FDA to approve over-the-counter topical NSAIDs,” Dr. Altman said. The FDA requires a new drug application for OTC topical NSAIDs demonstrating efficacy and safety, “as if they were completely new,” when the safety exceeds presently approved OTC oral NSAIDs and has already been shown for prescription topical NSAIDs, he said.

[email protected]

The coming year in rheumatology brings with it a variety of trends and concerns about how rheumatologists can chart the best course for their practices and patients amid mounting fiscal and regulatory pressures.

Questions also arise as to how rheumatology can improve its attractiveness to students and residents in 2016 with the current level of effort in mentoring, outreach, and competition against higher-paying subspecialties.

There’s also high interest and expectations in the new year for studies on systemic sclerosis and microbiome research, as well as questions about what the future holds for intra-articular hyaluronic acid and over-the-counter topical nonsteroidal anti-inflammatory drugs for osteoarthritis (OA).

Rheumatology News editorial advisory board members gave their thoughts on these areas of rheumatology in 2016.

Insurance and reimbursement problems

The changing landscape in insurance plans, brought about largely by the Affordable Care Act, is having a big impact on patients and physicians, particularly in Florida, where more than 1.5 million people signed up for an ACA federal marketplace plan in 2015. Difficulty in accessing and affording care in 2016 figures to be an even greater problem, said Dr. Norman Gaylis, who is in private practice in Aventura, Fla.

In general, many policies are passing an increased burden onto patients in regard to deductibles, copayments, and costs of medications, he said. “That’s putting tremendous stress on practices. I think this is nationwide, where we’re finding that rheumatology patients are not getting access to the drugs for [several] reasons: they’ve become unaffordable, the various pharmaceutical support programs have run out of money, and the amount of work that practices are now performing in trying to get authorization for the patients far exceeds any type of revenue [it] could be generating or should be generating to cover these increased costs. So essentially there’s a reduction in reimbursement and a reduction in revenue going along at the same time.”

Dr. Gaylis noted that there is “tremendous pressure” from all sides to reduce access to rheumatology drugs, which have rising costs. For instance, the cost of a monthly supply of generic celebrex in his practice’s area is on average $120-$200, “which is almost prohibitive for many of our patients.”

“We’re finding that this year [2015] alone, 20% of patients who are on standard infusion therapy as a routine part of their management of rheumatoid arthritis have basically dropped out,” he said. “If that’s equal across the board, that means a very high number of patients are not getting optimal care.”

The trend for rheumatologists, particularly those in solo practice, to make contracts with fewer insurance companies could accelerate in 2016, Dr. Gaylis said.

Some rheumatologists are beginning to not accept insured patients with coverage from managed care companies or the lower-tier payers, and “that’s a significant trend if it starts evolving because it will create a two-tiered system in that you’ll have the more affluent patient going to one of these practices, and then you’ll have clinics where you’ll have a totally different level of care.” Whether it builds up enough to where rheumatologists begin to develop hybrid concierge practices is a fair question, he said. “It’s very difficult to conceive of a patient paying for both primary care and subspecialist concierge service. But I am starting to see signals where there may well be some integration between concierge primary care and concierge subspecialties.”

Training, mentoring more rheumatologists

Another issue going into 2016 is the lack of mentoring and assistance to medical students and residents to draw them to the subspecialty and keep them there, as well as the viability of rheumatology as an attractive subspecialty. “It’s difficult to see how we can attract medical students and residents to the specialty when the cost of their education leaves them with staggering bills to be paid. You’ve got to be extremely passionate to want to be a rheumatologist,” Dr. Gaylis said.

Dr. Elizabeth Volkmann, clinical instructor in rheumatology at the University of California, Los Angeles, agreed and said she looked forward to seeing how the future of mentoring programs in rheumatology will progress in 2016 and beyond. She noted that the American College of Rheumatology (ACR)/Childhood Arthritis and Rheumatology Research Alliance Mentoring Interest Group (AMIGO), a career-mentoring program that serves most fellows and many junior faculty in pediatric rheumatology across the United States and Canada, recently reported success in establishing mentor contact, suitability of mentor-mentee pairing, as well as benefit with respect to career development, scholarship, and work-life balance, and was especially useful to fellows, compared with junior faculty (Arthritis Care Res. 2015 Sep 28. doi: 10.1002/acr.22732).

Dr. Volkmann expressed interest in seeing how the ACR’s Choose Rheumatology! mentorship program is performing. The program seeks to pair students and residents with rheumatologist mentors who will offer advice and help to guide them. She also pointed to the European League Against Rheumatism’s working group for young rheumatologists, the Emerging EULAR Network (EMEUNET), which seeks to promote the educational, research, and mentoring needs of young clinicians and researchers in rheumatology in Europe. as a potential model for the ACR to use in the United States.

Some of the conference-based resources available to rheumatology fellows include the ACR’s 2016 State-of-the-Art Clinical Symposium, which provides a presymposium course specifically for fellows and has sessions on choosing career paths, and the Rheumatology Research Workshop, which targets rheumatologists interested in pursuing an academic research career. Fellows-in-training travel scholarships are available for both conferences.

New systemic sclerosis and microbiome research

Many new studies in systemic sclerosis will build on results obtained in earlier-phase trials or unanswered questions arising out of treatment comparison studies. “It is a very exciting time in the world of scleroderma,” said Dr. Virginia Steen, professor of medicine at Georgetown University, Washington.

At least four new trials are studying treatments for skin manifestations of systemic sclerosis, noted Dr. Steen. In patients with diffuse cutaneous systemic sclerosis, the phase II ASSET study is testing abatacept (Orencia) against placebo and another phase II study is testing riociguat (Adempas). Roche has started enrolling patients for a phase III trial of tocilizumab (Actemra) on the heels of positive findings from its phase II study. Dr. Steen and colleagues at Johns Hopkins University are also finishing up a pilot study of the effects of intravenous immunoglobulin (Privigen) on skin disease in systemic sclerosis and should have results ready for 2016.

Two additional trials will be investigating treatments for interstitial lung disease associated with systemic sclerosis: the Scleroderma Lung Study III, testing the use of mycophenolate mofetil in all patients with the addition of pirfenidone (Esbriet) or placebo, and a separate phase III study of nintedanib (Ofev) vs. placebo that just began enrolling patients.

There are also several trials of add-on therapies, including topical nitroglycerin for Raynaud’s phenomenon or riociguat for digital ulcers, and another that is testing autologous adipose–derived regenerative cells for the treatment of hand dysfunction.

In addition to these trials now underway, the expected 2016 publication of the validation of the Combined Response Index for Systemic Sclerosis will hopefully “lead to real movement forward in the treatment of systemic sclerosis,” said Dr. Daniel E. Furst, the Carl Pearson Professor of Medicine at University of California, Los Angeles.

Further examination of the Wnt signaling pathway in systemic sclerosis should also bring better insights into the disease’s pathogenesis and potential for treatment, Dr. Furst noted, as recent experimental results have shown that its activation induces fibroblast activation with subsequent myofibroblast differentiation and excessive collagen release. Small-molecule inhibitors of Wnt signaling in early clinical trials have shown promising results.

Dr. Furst and Dr. Volkmann said they also hope for studies describing better and more specific data regarding the microbiome in rheumatic disease, especially systemic sclerosis and rheumatoid arthritis, both of which have microbiome data linked with clinically meaningful outcomes (Nat Med. 2015 Aug;21[8]:895-905).

An important unanswered question, Dr. Volkmann said, is whether differences found in GI microbial composition between diseases and between different disease subtypes are clinically meaningful.

OA treatments: AAOS guidelines, OTC topical NSAIDs

The repercussions of the American Academy of Orthopaedic Surgeons 2013 clinical practice guideline’s statement on intra-articular hyaluronic acid treatment of knee OA will continue to be felt in 2016, according to Dr. Roy D. Altman, professor emeritus of medicine at University of California, Los Angeles.

The AAOS took a different stance from all other recent treatment guidelines for knee OA by stating: “Intra-articular hyaluronic acid is no longer recommended as a method of treatment for patients with symptomatic osteoarthritis of the knee.” The AAOS’s recommendation didn’t create much confusion with physicians and patients because its use continues to increase, but instead it has contributed to “a plethora of contradictory publications and increasing resistance on coverage by insurance carriers,” Dr. Altman said.

Another unresolved issue in OA treatment is “the resistance of the FDA to approve over-the-counter topical NSAIDs,” Dr. Altman said. The FDA requires a new drug application for OTC topical NSAIDs demonstrating efficacy and safety, “as if they were completely new,” when the safety exceeds presently approved OTC oral NSAIDs and has already been shown for prescription topical NSAIDs, he said.

[email protected]

The coming year in rheumatology brings with it a variety of trends and concerns about how rheumatologists can chart the best course for their practices and patients amid mounting fiscal and regulatory pressures.

Questions also arise as to how rheumatology can improve its attractiveness to students and residents in 2016 with the current level of effort in mentoring, outreach, and competition against higher-paying subspecialties.

There’s also high interest and expectations in the new year for studies on systemic sclerosis and microbiome research, as well as questions about what the future holds for intra-articular hyaluronic acid and over-the-counter topical nonsteroidal anti-inflammatory drugs for osteoarthritis (OA).

Rheumatology News editorial advisory board members gave their thoughts on these areas of rheumatology in 2016.

Insurance and reimbursement problems

The changing landscape in insurance plans, brought about largely by the Affordable Care Act, is having a big impact on patients and physicians, particularly in Florida, where more than 1.5 million people signed up for an ACA federal marketplace plan in 2015. Difficulty in accessing and affording care in 2016 figures to be an even greater problem, said Dr. Norman Gaylis, who is in private practice in Aventura, Fla.

In general, many policies are passing an increased burden onto patients in regard to deductibles, copayments, and costs of medications, he said. “That’s putting tremendous stress on practices. I think this is nationwide, where we’re finding that rheumatology patients are not getting access to the drugs for [several] reasons: they’ve become unaffordable, the various pharmaceutical support programs have run out of money, and the amount of work that practices are now performing in trying to get authorization for the patients far exceeds any type of revenue [it] could be generating or should be generating to cover these increased costs. So essentially there’s a reduction in reimbursement and a reduction in revenue going along at the same time.”

Dr. Gaylis noted that there is “tremendous pressure” from all sides to reduce access to rheumatology drugs, which have rising costs. For instance, the cost of a monthly supply of generic celebrex in his practice’s area is on average $120-$200, “which is almost prohibitive for many of our patients.”

“We’re finding that this year [2015] alone, 20% of patients who are on standard infusion therapy as a routine part of their management of rheumatoid arthritis have basically dropped out,” he said. “If that’s equal across the board, that means a very high number of patients are not getting optimal care.”

The trend for rheumatologists, particularly those in solo practice, to make contracts with fewer insurance companies could accelerate in 2016, Dr. Gaylis said.

Some rheumatologists are beginning to not accept insured patients with coverage from managed care companies or the lower-tier payers, and “that’s a significant trend if it starts evolving because it will create a two-tiered system in that you’ll have the more affluent patient going to one of these practices, and then you’ll have clinics where you’ll have a totally different level of care.” Whether it builds up enough to where rheumatologists begin to develop hybrid concierge practices is a fair question, he said. “It’s very difficult to conceive of a patient paying for both primary care and subspecialist concierge service. But I am starting to see signals where there may well be some integration between concierge primary care and concierge subspecialties.”

Training, mentoring more rheumatologists

Another issue going into 2016 is the lack of mentoring and assistance to medical students and residents to draw them to the subspecialty and keep them there, as well as the viability of rheumatology as an attractive subspecialty. “It’s difficult to see how we can attract medical students and residents to the specialty when the cost of their education leaves them with staggering bills to be paid. You’ve got to be extremely passionate to want to be a rheumatologist,” Dr. Gaylis said.

Dr. Elizabeth Volkmann, clinical instructor in rheumatology at the University of California, Los Angeles, agreed and said she looked forward to seeing how the future of mentoring programs in rheumatology will progress in 2016 and beyond. She noted that the American College of Rheumatology (ACR)/Childhood Arthritis and Rheumatology Research Alliance Mentoring Interest Group (AMIGO), a career-mentoring program that serves most fellows and many junior faculty in pediatric rheumatology across the United States and Canada, recently reported success in establishing mentor contact, suitability of mentor-mentee pairing, as well as benefit with respect to career development, scholarship, and work-life balance, and was especially useful to fellows, compared with junior faculty (Arthritis Care Res. 2015 Sep 28. doi: 10.1002/acr.22732).

Dr. Volkmann expressed interest in seeing how the ACR’s Choose Rheumatology! mentorship program is performing. The program seeks to pair students and residents with rheumatologist mentors who will offer advice and help to guide them. She also pointed to the European League Against Rheumatism’s working group for young rheumatologists, the Emerging EULAR Network (EMEUNET), which seeks to promote the educational, research, and mentoring needs of young clinicians and researchers in rheumatology in Europe. as a potential model for the ACR to use in the United States.

Some of the conference-based resources available to rheumatology fellows include the ACR’s 2016 State-of-the-Art Clinical Symposium, which provides a presymposium course specifically for fellows and has sessions on choosing career paths, and the Rheumatology Research Workshop, which targets rheumatologists interested in pursuing an academic research career. Fellows-in-training travel scholarships are available for both conferences.

New systemic sclerosis and microbiome research

Many new studies in systemic sclerosis will build on results obtained in earlier-phase trials or unanswered questions arising out of treatment comparison studies. “It is a very exciting time in the world of scleroderma,” said Dr. Virginia Steen, professor of medicine at Georgetown University, Washington.

At least four new trials are studying treatments for skin manifestations of systemic sclerosis, noted Dr. Steen. In patients with diffuse cutaneous systemic sclerosis, the phase II ASSET study is testing abatacept (Orencia) against placebo and another phase II study is testing riociguat (Adempas). Roche has started enrolling patients for a phase III trial of tocilizumab (Actemra) on the heels of positive findings from its phase II study. Dr. Steen and colleagues at Johns Hopkins University are also finishing up a pilot study of the effects of intravenous immunoglobulin (Privigen) on skin disease in systemic sclerosis and should have results ready for 2016.

Two additional trials will be investigating treatments for interstitial lung disease associated with systemic sclerosis: the Scleroderma Lung Study III, testing the use of mycophenolate mofetil in all patients with the addition of pirfenidone (Esbriet) or placebo, and a separate phase III study of nintedanib (Ofev) vs. placebo that just began enrolling patients.

There are also several trials of add-on therapies, including topical nitroglycerin for Raynaud’s phenomenon or riociguat for digital ulcers, and another that is testing autologous adipose–derived regenerative cells for the treatment of hand dysfunction.

In addition to these trials now underway, the expected 2016 publication of the validation of the Combined Response Index for Systemic Sclerosis will hopefully “lead to real movement forward in the treatment of systemic sclerosis,” said Dr. Daniel E. Furst, the Carl Pearson Professor of Medicine at University of California, Los Angeles.

Further examination of the Wnt signaling pathway in systemic sclerosis should also bring better insights into the disease’s pathogenesis and potential for treatment, Dr. Furst noted, as recent experimental results have shown that its activation induces fibroblast activation with subsequent myofibroblast differentiation and excessive collagen release. Small-molecule inhibitors of Wnt signaling in early clinical trials have shown promising results.

Dr. Furst and Dr. Volkmann said they also hope for studies describing better and more specific data regarding the microbiome in rheumatic disease, especially systemic sclerosis and rheumatoid arthritis, both of which have microbiome data linked with clinically meaningful outcomes (Nat Med. 2015 Aug;21[8]:895-905).

An important unanswered question, Dr. Volkmann said, is whether differences found in GI microbial composition between diseases and between different disease subtypes are clinically meaningful.

OA treatments: AAOS guidelines, OTC topical NSAIDs

The repercussions of the American Academy of Orthopaedic Surgeons 2013 clinical practice guideline’s statement on intra-articular hyaluronic acid treatment of knee OA will continue to be felt in 2016, according to Dr. Roy D. Altman, professor emeritus of medicine at University of California, Los Angeles.

The AAOS took a different stance from all other recent treatment guidelines for knee OA by stating: “Intra-articular hyaluronic acid is no longer recommended as a method of treatment for patients with symptomatic osteoarthritis of the knee.” The AAOS’s recommendation didn’t create much confusion with physicians and patients because its use continues to increase, but instead it has contributed to “a plethora of contradictory publications and increasing resistance on coverage by insurance carriers,” Dr. Altman said.

Another unresolved issue in OA treatment is “the resistance of the FDA to approve over-the-counter topical NSAIDs,” Dr. Altman said. The FDA requires a new drug application for OTC topical NSAIDs demonstrating efficacy and safety, “as if they were completely new,” when the safety exceeds presently approved OTC oral NSAIDs and has already been shown for prescription topical NSAIDs, he said.

[email protected]

Women with knee osteoarthritis who had low thigh muscle strength were more likely to need a knee replacement in a case-control study of participants in the Osteoarthritis Initiative (OAI).

In particular, predictors of knee replacement included knee extensor weakness in the year prior to knee replacement and longitudinal deterioration in knee extensor strength over a 2-year observation period prior to surgery. Measurement of knee extensor strength in women with knee osteoarthritis may then indicate who could benefit from weight training exercises to potentially delay or prevent the need for knee replacement surgery, said the researchers, led by Dr. Adam Culvenor of Paracelsus Medical University in Salzburg, Austria (Arthritis Rheumatol. 2015 Dec 14. doi: 10.1002/art.39540).

The optimal knee extensor strength threshold for differentiating those with and without knee replacement risk was approximately 200 N or 0.9 Nm/kg; or prevention of any loss of knee extensor strength over 2 years.

©pixologicstudio/thinkstockphotos.com

“There appears to be a considerable window for women below this threshold to obtain realistic strength gains and potentially lower the risk of knee replacement,” the study authors concluded.

In the multicenter, longitudinal, case-control study of 4,796 participants in the OAI (60% of whom were women), the investigators identified 136 participants who had received a knee replacement and matched them with controls who had not received a knee replacement and were similar in age, body mass index (BMI), and radiographic stage. The mean age of the women was 65 years and the mean BMI was 29 kg/m².

The results showed that knee extensor strength at the examination prior to knee replacement (time T₀), which occurred 2 years or less before surgery, was significantly lower in females who had received a knee replacement than in matched controls (pain-adjusted odds ratio, 1.72; 95% confidence interval, 1.16-2.56; P = .007). Measurement of the longitudinal change in knee extensor and flexor strength between T₀ and 2 years prior to T₀ (T_-2) also provided similar results (pain-adjusted OR, 4.30; 95% CI, 1.34-13.79; P = .014). The findings were independent of age, BMI, and radiographic disease severity, the researchers noted.

The investigators found no relationship between knee extensor or flexor muscle strength in men and subsequent need for knee replacement surgery. The relationship between thigh muscle strength and knee replacement for women did not extend to measurements made at T_-2 or T_-4 or the change in thigh muscle strength between T_-2 and T_-4.

The OAI receives funding from the National Institutes of Health, Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. The work was also funded by a grant from the European Union Seventh Framework Programme. One author disclosed consulting or preparing educational sessions for pharmaceutical companies and for receiving research support. Two authors reported being employees of Chondrometrics GmbH, a company providing MR image analysis services to academic researchers and to industry.

Women with knee osteoarthritis who had low thigh muscle strength were more likely to need a knee replacement in a case-control study of participants in the Osteoarthritis Initiative (OAI).

In particular, predictors of knee replacement included knee extensor weakness in the year prior to knee replacement and longitudinal deterioration in knee extensor strength over a 2-year observation period prior to surgery. Measurement of knee extensor strength in women with knee osteoarthritis may then indicate who could benefit from weight training exercises to potentially delay or prevent the need for knee replacement surgery, said the researchers, led by Dr. Adam Culvenor of Paracelsus Medical University in Salzburg, Austria (Arthritis Rheumatol. 2015 Dec 14. doi: 10.1002/art.39540).

The optimal knee extensor strength threshold for differentiating those with and without knee replacement risk was approximately 200 N or 0.9 Nm/kg; or prevention of any loss of knee extensor strength over 2 years.

©pixologicstudio/thinkstockphotos.com

“There appears to be a considerable window for women below this threshold to obtain realistic strength gains and potentially lower the risk of knee replacement,” the study authors concluded.

In the multicenter, longitudinal, case-control study of 4,796 participants in the OAI (60% of whom were women), the investigators identified 136 participants who had received a knee replacement and matched them with controls who had not received a knee replacement and were similar in age, body mass index (BMI), and radiographic stage. The mean age of the women was 65 years and the mean BMI was 29 kg/m².

The results showed that knee extensor strength at the examination prior to knee replacement (time T₀), which occurred 2 years or less before surgery, was significantly lower in females who had received a knee replacement than in matched controls (pain-adjusted odds ratio, 1.72; 95% confidence interval, 1.16-2.56; P = .007). Measurement of the longitudinal change in knee extensor and flexor strength between T₀ and 2 years prior to T₀ (T_-2) also provided similar results (pain-adjusted OR, 4.30; 95% CI, 1.34-13.79; P = .014). The findings were independent of age, BMI, and radiographic disease severity, the researchers noted.

The investigators found no relationship between knee extensor or flexor muscle strength in men and subsequent need for knee replacement surgery. The relationship between thigh muscle strength and knee replacement for women did not extend to measurements made at T_-2 or T_-4 or the change in thigh muscle strength between T_-2 and T_-4.

The OAI receives funding from the National Institutes of Health, Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. The work was also funded by a grant from the European Union Seventh Framework Programme. One author disclosed consulting or preparing educational sessions for pharmaceutical companies and for receiving research support. Two authors reported being employees of Chondrometrics GmbH, a company providing MR image analysis services to academic researchers and to industry.

Women with knee osteoarthritis who had low thigh muscle strength were more likely to need a knee replacement in a case-control study of participants in the Osteoarthritis Initiative (OAI).

In particular, predictors of knee replacement included knee extensor weakness in the year prior to knee replacement and longitudinal deterioration in knee extensor strength over a 2-year observation period prior to surgery. Measurement of knee extensor strength in women with knee osteoarthritis may then indicate who could benefit from weight training exercises to potentially delay or prevent the need for knee replacement surgery, said the researchers, led by Dr. Adam Culvenor of Paracelsus Medical University in Salzburg, Austria (Arthritis Rheumatol. 2015 Dec 14. doi: 10.1002/art.39540).

The optimal knee extensor strength threshold for differentiating those with and without knee replacement risk was approximately 200 N or 0.9 Nm/kg; or prevention of any loss of knee extensor strength over 2 years.

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“There appears to be a considerable window for women below this threshold to obtain realistic strength gains and potentially lower the risk of knee replacement,” the study authors concluded.

In the multicenter, longitudinal, case-control study of 4,796 participants in the OAI (60% of whom were women), the investigators identified 136 participants who had received a knee replacement and matched them with controls who had not received a knee replacement and were similar in age, body mass index (BMI), and radiographic stage. The mean age of the women was 65 years and the mean BMI was 29 kg/m².

The results showed that knee extensor strength at the examination prior to knee replacement (time T₀), which occurred 2 years or less before surgery, was significantly lower in females who had received a knee replacement than in matched controls (pain-adjusted odds ratio, 1.72; 95% confidence interval, 1.16-2.56; P = .007). Measurement of the longitudinal change in knee extensor and flexor strength between T₀ and 2 years prior to T₀ (T_-2) also provided similar results (pain-adjusted OR, 4.30; 95% CI, 1.34-13.79; P = .014). The findings were independent of age, BMI, and radiographic disease severity, the researchers noted.

The investigators found no relationship between knee extensor or flexor muscle strength in men and subsequent need for knee replacement surgery. The relationship between thigh muscle strength and knee replacement for women did not extend to measurements made at T_-2 or T_-4 or the change in thigh muscle strength between T_-2 and T_-4.

The OAI receives funding from the National Institutes of Health, Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. The work was also funded by a grant from the European Union Seventh Framework Programme. One author disclosed consulting or preparing educational sessions for pharmaceutical companies and for receiving research support. Two authors reported being employees of Chondrometrics GmbH, a company providing MR image analysis services to academic researchers and to industry.