Osteoarthritis

TORONTO – A Swedish national primary care–centered self-management program for patients with knee or hip osteoarthritis (OA) resulted in clinically meaningful improvements through 1 year of follow-up in an observational registry study of 47,035 participants, Therese S. Jönsson reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“The BOA [Better management of patients with Osteoarthritis] program is feasible and demonstrates positive results in a large clinical context. Our results indicate that offering this intervention as the first-line treatment for patients with hip and knee osteoarthritis may reduce the burden of disease,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Indeed, the results of the Swedish BOA program for nonsurgical treatment of OA played an influential role in the new draft of OARSI guidelines for management of knee osteoarthritis. The program could serve as a template for implementation of a similar approach in other health care settings. The BOA program has been rolled out to more than 700 Swedish primary care practice sites, according to Ms. Jönsson, a PhD student at Lund (Sweden) University.

The program was created to meet a defined national goal that, as early as possible in the course of the disease, every Swedish patient with knee or hip OA should receive education about their disease and the importance of exercise as a means of improving their quality of life. The impetus for BOA was a widespread concern that, in Sweden and elsewhere, far too many OA patients were being referred for joint surgery without ever having tried the evidence-based core nonsurgical treatments.
 

The BOA intervention

Following patient referral by a primary care physician, the Swedish BOA program starts off with individual assessment and biomechanical testing by a physical therapist. This is followed by two small-group education sessions of about 90 minutes led by a physical therapist or occupational therapist. Session one includes information about the pathology of OA, risk factors, symptoms, and the available treatments. Session two focuses on coping skills, self-management strategies to reduce pain and symptoms, the central role of exercise as a core treatment in OA, and ways to incorporate physical activity into daily living.

Then comes a decision point. Having listened to a motivational message extolling the benefits of exercise as a means of empowering self-management of their chronic disease, participants next have three choices: They can attend supervised group exercise classes twice weekly for 6 weeks to kick-start a more physically active lifestyle, they can start an individually adapted home exercise program, or they can decline exercise.

Giving patients a choice in this matter is a strategy rooted in the psychological concept of motivational stages of change, which recognizes that some patients with a chronic illness whose course is modifiable through lifestyle change are initially in a precontemplation stage of change. And pushing them hard at that point is counterproductive. The home exercise option, which permits patients to take a low-and-slow approach to exercise, is based upon the BOA program developers’ stated philosophy that 5 minutes of exercise daily, performed as part of everyday life, has a bigger impact upon function than does a 30-minute exercise program that’s abandoned after a few weeks. The goal of the BOA program is for patients to eventually build up to at least 150 minutes of moderate-intensity exercise per week.
 

The results

Roughly 15% of patients enrolled in the registry declined the exercise option. Ms. Jönsson’s analysis focused on those who opted to participate in an exercise program, 40% of whom selected the home exercise option. This analysis included 30,682 patients with knee OA and 16,363 with hip OA. They returned to the physical therapist for a face-to-face reassessment after 3 months, and they completed a mailed outcome-oriented questionnaire at 12 months.

The BOA intervention was more effective in reducing pain in the knee OA group than in those with hip OA. A statistically significant reduction in self-assessed pain scores on a 0-10 scale was seen in both the knee and hip OA groups at 3 and 12 months; however, only the knee OA patients achieved a clinically important decrease in pain, defined as at least a 15% drop in pain scores. Their pain scores improved from 5.24 at baseline to 4.07 at 3 months and 4.23 at 12 months. In the hip OA patients, pain scores went from 5.39 at baseline to 4.56 at 3 months and 4.7 at 12 months.

However, at 3 and 12 months, significantly fewer patients in both the hip and knee OA groups reported experiencing pain more than once per week, compared with baseline. They also took fewer pain-killing medications, reported less avoidance behavior involving fear of movement, were less willing to undergo joint surgery, and scored significantly higher on the five-level EQ-5D quality-of-life measure than at baseline. Moreover, fewer patients were on sick leave at the 12-month follow-up than at baseline, an outcome that wasn’t assessed at 3 months.

Adherence to the group exercise classes was “quite low,” according to Ms. Jönsson, and poor adherence was reflected in smaller reductions in pain scores. Only 30% of patients who elected the supervised group exercise option attended 10 of the 12 sessions, she noted.

Ms. Jönsson reported having no financial conflicts regarding her study. The BOA program is funded by the Swedish government.

[email protected]

SOURCE: Jönsson TS et al. Osteoarthritis Cartilage. 2019 Apr;27(suppl 1):S497, Abstract 717.

TORONTO – A Swedish national primary care–centered self-management program for patients with knee or hip osteoarthritis (OA) resulted in clinically meaningful improvements through 1 year of follow-up in an observational registry study of 47,035 participants, Therese S. Jönsson reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“The BOA [Better management of patients with Osteoarthritis] program is feasible and demonstrates positive results in a large clinical context. Our results indicate that offering this intervention as the first-line treatment for patients with hip and knee osteoarthritis may reduce the burden of disease,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Indeed, the results of the Swedish BOA program for nonsurgical treatment of OA played an influential role in the new draft of OARSI guidelines for management of knee osteoarthritis. The program could serve as a template for implementation of a similar approach in other health care settings. The BOA program has been rolled out to more than 700 Swedish primary care practice sites, according to Ms. Jönsson, a PhD student at Lund (Sweden) University.

The program was created to meet a defined national goal that, as early as possible in the course of the disease, every Swedish patient with knee or hip OA should receive education about their disease and the importance of exercise as a means of improving their quality of life. The impetus for BOA was a widespread concern that, in Sweden and elsewhere, far too many OA patients were being referred for joint surgery without ever having tried the evidence-based core nonsurgical treatments.
 

The BOA intervention

Following patient referral by a primary care physician, the Swedish BOA program starts off with individual assessment and biomechanical testing by a physical therapist. This is followed by two small-group education sessions of about 90 minutes led by a physical therapist or occupational therapist. Session one includes information about the pathology of OA, risk factors, symptoms, and the available treatments. Session two focuses on coping skills, self-management strategies to reduce pain and symptoms, the central role of exercise as a core treatment in OA, and ways to incorporate physical activity into daily living.

Then comes a decision point. Having listened to a motivational message extolling the benefits of exercise as a means of empowering self-management of their chronic disease, participants next have three choices: They can attend supervised group exercise classes twice weekly for 6 weeks to kick-start a more physically active lifestyle, they can start an individually adapted home exercise program, or they can decline exercise.

Giving patients a choice in this matter is a strategy rooted in the psychological concept of motivational stages of change, which recognizes that some patients with a chronic illness whose course is modifiable through lifestyle change are initially in a precontemplation stage of change. And pushing them hard at that point is counterproductive. The home exercise option, which permits patients to take a low-and-slow approach to exercise, is based upon the BOA program developers’ stated philosophy that 5 minutes of exercise daily, performed as part of everyday life, has a bigger impact upon function than does a 30-minute exercise program that’s abandoned after a few weeks. The goal of the BOA program is for patients to eventually build up to at least 150 minutes of moderate-intensity exercise per week.
 

The results

Roughly 15% of patients enrolled in the registry declined the exercise option. Ms. Jönsson’s analysis focused on those who opted to participate in an exercise program, 40% of whom selected the home exercise option. This analysis included 30,682 patients with knee OA and 16,363 with hip OA. They returned to the physical therapist for a face-to-face reassessment after 3 months, and they completed a mailed outcome-oriented questionnaire at 12 months.

The BOA intervention was more effective in reducing pain in the knee OA group than in those with hip OA. A statistically significant reduction in self-assessed pain scores on a 0-10 scale was seen in both the knee and hip OA groups at 3 and 12 months; however, only the knee OA patients achieved a clinically important decrease in pain, defined as at least a 15% drop in pain scores. Their pain scores improved from 5.24 at baseline to 4.07 at 3 months and 4.23 at 12 months. In the hip OA patients, pain scores went from 5.39 at baseline to 4.56 at 3 months and 4.7 at 12 months.

However, at 3 and 12 months, significantly fewer patients in both the hip and knee OA groups reported experiencing pain more than once per week, compared with baseline. They also took fewer pain-killing medications, reported less avoidance behavior involving fear of movement, were less willing to undergo joint surgery, and scored significantly higher on the five-level EQ-5D quality-of-life measure than at baseline. Moreover, fewer patients were on sick leave at the 12-month follow-up than at baseline, an outcome that wasn’t assessed at 3 months.

Adherence to the group exercise classes was “quite low,” according to Ms. Jönsson, and poor adherence was reflected in smaller reductions in pain scores. Only 30% of patients who elected the supervised group exercise option attended 10 of the 12 sessions, she noted.

Ms. Jönsson reported having no financial conflicts regarding her study. The BOA program is funded by the Swedish government.

[email protected]

SOURCE: Jönsson TS et al. Osteoarthritis Cartilage. 2019 Apr;27(suppl 1):S497, Abstract 717.

TORONTO – A Swedish national primary care–centered self-management program for patients with knee or hip osteoarthritis (OA) resulted in clinically meaningful improvements through 1 year of follow-up in an observational registry study of 47,035 participants, Therese S. Jönsson reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“The BOA [Better management of patients with Osteoarthritis] program is feasible and demonstrates positive results in a large clinical context. Our results indicate that offering this intervention as the first-line treatment for patients with hip and knee osteoarthritis may reduce the burden of disease,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Indeed, the results of the Swedish BOA program for nonsurgical treatment of OA played an influential role in the new draft of OARSI guidelines for management of knee osteoarthritis. The program could serve as a template for implementation of a similar approach in other health care settings. The BOA program has been rolled out to more than 700 Swedish primary care practice sites, according to Ms. Jönsson, a PhD student at Lund (Sweden) University.

The program was created to meet a defined national goal that, as early as possible in the course of the disease, every Swedish patient with knee or hip OA should receive education about their disease and the importance of exercise as a means of improving their quality of life. The impetus for BOA was a widespread concern that, in Sweden and elsewhere, far too many OA patients were being referred for joint surgery without ever having tried the evidence-based core nonsurgical treatments.
 

The BOA intervention

Following patient referral by a primary care physician, the Swedish BOA program starts off with individual assessment and biomechanical testing by a physical therapist. This is followed by two small-group education sessions of about 90 minutes led by a physical therapist or occupational therapist. Session one includes information about the pathology of OA, risk factors, symptoms, and the available treatments. Session two focuses on coping skills, self-management strategies to reduce pain and symptoms, the central role of exercise as a core treatment in OA, and ways to incorporate physical activity into daily living.

Then comes a decision point. Having listened to a motivational message extolling the benefits of exercise as a means of empowering self-management of their chronic disease, participants next have three choices: They can attend supervised group exercise classes twice weekly for 6 weeks to kick-start a more physically active lifestyle, they can start an individually adapted home exercise program, or they can decline exercise.

Giving patients a choice in this matter is a strategy rooted in the psychological concept of motivational stages of change, which recognizes that some patients with a chronic illness whose course is modifiable through lifestyle change are initially in a precontemplation stage of change. And pushing them hard at that point is counterproductive. The home exercise option, which permits patients to take a low-and-slow approach to exercise, is based upon the BOA program developers’ stated philosophy that 5 minutes of exercise daily, performed as part of everyday life, has a bigger impact upon function than does a 30-minute exercise program that’s abandoned after a few weeks. The goal of the BOA program is for patients to eventually build up to at least 150 minutes of moderate-intensity exercise per week.
 

The results

Roughly 15% of patients enrolled in the registry declined the exercise option. Ms. Jönsson’s analysis focused on those who opted to participate in an exercise program, 40% of whom selected the home exercise option. This analysis included 30,682 patients with knee OA and 16,363 with hip OA. They returned to the physical therapist for a face-to-face reassessment after 3 months, and they completed a mailed outcome-oriented questionnaire at 12 months.

The BOA intervention was more effective in reducing pain in the knee OA group than in those with hip OA. A statistically significant reduction in self-assessed pain scores on a 0-10 scale was seen in both the knee and hip OA groups at 3 and 12 months; however, only the knee OA patients achieved a clinically important decrease in pain, defined as at least a 15% drop in pain scores. Their pain scores improved from 5.24 at baseline to 4.07 at 3 months and 4.23 at 12 months. In the hip OA patients, pain scores went from 5.39 at baseline to 4.56 at 3 months and 4.7 at 12 months.

However, at 3 and 12 months, significantly fewer patients in both the hip and knee OA groups reported experiencing pain more than once per week, compared with baseline. They also took fewer pain-killing medications, reported less avoidance behavior involving fear of movement, were less willing to undergo joint surgery, and scored significantly higher on the five-level EQ-5D quality-of-life measure than at baseline. Moreover, fewer patients were on sick leave at the 12-month follow-up than at baseline, an outcome that wasn’t assessed at 3 months.

Adherence to the group exercise classes was “quite low,” according to Ms. Jönsson, and poor adherence was reflected in smaller reductions in pain scores. Only 30% of patients who elected the supervised group exercise option attended 10 of the 12 sessions, she noted.

Ms. Jönsson reported having no financial conflicts regarding her study. The BOA program is funded by the Swedish government.

[email protected]

SOURCE: Jönsson TS et al. Osteoarthritis Cartilage. 2019 Apr;27(suppl 1):S497, Abstract 717.

TORONTO – Osteoarthritis research doesn’t get nearly the respect it deserves in the medical literature, Elizabeth M. Badley, PhD, asserted at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Osteoarthritis is by far the most common type of arthritis. There are easily 10 times more people who have osteoarthritis than any other joint disease, but when you look at the literature, the situation is kind of reversed. Osteoarthritis is brushed off by society to a degree,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Bradley and colleagues performed a search of MEDLINE for 2007-2016, which turned up a total of 1,625 publications in 2016 on osteoarthritis, excluding those with an orthopedic surgery focus, compared with 10,904 results regarding the broader topic of joint diseases and 28,932 on musculoskeletal diseases.

The bottom line: “Progress is slow, and at this rate osteoarthritis will not be receiving the attention it deserves in our lifetime,” said Dr. Badley, of the department of epidemiology at the University of Toronto and a senior scientist at the Krembil Research Institute, also in Toronto.

The number of publications per year devoted to OA rose by a robust 88% during 2007-2016, while the number on OA not focused on orthopedic procedures grew by 65%. Both of these increases were greater than those for publications on musculoskeletal diseases and joint diseases overall, which were 41% and 51%, respectively. But the absolute number of OA publications was dwarfed by the numbers of those in the other search categories. For example, the number of publications on OA without an orthopedic surgery thrust was 985 in 2007, compared with 7,204 on joint diseases overall.

Among the striking findings of the investigators’ study of the medical literature was the disconnect between the amount of attention devoted to some of the joint-specific manifestations of OA and the actual prevalence of these conditions in the population. For example, the prevalence of hand OA in people living with OA was 52% according to the 2009 Survey on Living with Chronic Diseases in Canada, conducted by Statistics Canada, yet only 6.5% of the publications on OA in 2016 were devoted to hand/thumb OA. Similarly, the prevalence of spine OA was 52% among Canadians with OA, but only 4.3% of OA publications in 2016 focused on that topic. And while the number of publications devoted to elbow OA soared by a seemingly impressive 233% during the study period, the actual numbers were 3 publications in 2007 and 10 in 2016.

“Also, the average number of affected joints in people with osteoarthritis is four. Yet very, very few papers are about multijoint osteoarthritis. And when they do talk about multijoint osteoarthritis, they’re still only talking about hand/hip/knee. So we’re missing the bigger picture of osteoarthritis as a multijoint disease. We’re missing the spine, largely, as a part of osteoarthritis, and we’re missing the peripheral joints,” she said.

Dr. Badley reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Badley EM et al. Osteoarthritis Cartilage. 2019 Apr;27(Suppl 1):S278, Abstract 393.

TORONTO – Osteoarthritis research doesn’t get nearly the respect it deserves in the medical literature, Elizabeth M. Badley, PhD, asserted at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Osteoarthritis is by far the most common type of arthritis. There are easily 10 times more people who have osteoarthritis than any other joint disease, but when you look at the literature, the situation is kind of reversed. Osteoarthritis is brushed off by society to a degree,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Bradley and colleagues performed a search of MEDLINE for 2007-2016, which turned up a total of 1,625 publications in 2016 on osteoarthritis, excluding those with an orthopedic surgery focus, compared with 10,904 results regarding the broader topic of joint diseases and 28,932 on musculoskeletal diseases.

The bottom line: “Progress is slow, and at this rate osteoarthritis will not be receiving the attention it deserves in our lifetime,” said Dr. Badley, of the department of epidemiology at the University of Toronto and a senior scientist at the Krembil Research Institute, also in Toronto.

The number of publications per year devoted to OA rose by a robust 88% during 2007-2016, while the number on OA not focused on orthopedic procedures grew by 65%. Both of these increases were greater than those for publications on musculoskeletal diseases and joint diseases overall, which were 41% and 51%, respectively. But the absolute number of OA publications was dwarfed by the numbers of those in the other search categories. For example, the number of publications on OA without an orthopedic surgery thrust was 985 in 2007, compared with 7,204 on joint diseases overall.

Among the striking findings of the investigators’ study of the medical literature was the disconnect between the amount of attention devoted to some of the joint-specific manifestations of OA and the actual prevalence of these conditions in the population. For example, the prevalence of hand OA in people living with OA was 52% according to the 2009 Survey on Living with Chronic Diseases in Canada, conducted by Statistics Canada, yet only 6.5% of the publications on OA in 2016 were devoted to hand/thumb OA. Similarly, the prevalence of spine OA was 52% among Canadians with OA, but only 4.3% of OA publications in 2016 focused on that topic. And while the number of publications devoted to elbow OA soared by a seemingly impressive 233% during the study period, the actual numbers were 3 publications in 2007 and 10 in 2016.

“Also, the average number of affected joints in people with osteoarthritis is four. Yet very, very few papers are about multijoint osteoarthritis. And when they do talk about multijoint osteoarthritis, they’re still only talking about hand/hip/knee. So we’re missing the bigger picture of osteoarthritis as a multijoint disease. We’re missing the spine, largely, as a part of osteoarthritis, and we’re missing the peripheral joints,” she said.

Dr. Badley reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Badley EM et al. Osteoarthritis Cartilage. 2019 Apr;27(Suppl 1):S278, Abstract 393.

TORONTO – Osteoarthritis research doesn’t get nearly the respect it deserves in the medical literature, Elizabeth M. Badley, PhD, asserted at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Osteoarthritis is by far the most common type of arthritis. There are easily 10 times more people who have osteoarthritis than any other joint disease, but when you look at the literature, the situation is kind of reversed. Osteoarthritis is brushed off by society to a degree,” she said at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Bradley and colleagues performed a search of MEDLINE for 2007-2016, which turned up a total of 1,625 publications in 2016 on osteoarthritis, excluding those with an orthopedic surgery focus, compared with 10,904 results regarding the broader topic of joint diseases and 28,932 on musculoskeletal diseases.

The bottom line: “Progress is slow, and at this rate osteoarthritis will not be receiving the attention it deserves in our lifetime,” said Dr. Badley, of the department of epidemiology at the University of Toronto and a senior scientist at the Krembil Research Institute, also in Toronto.

The number of publications per year devoted to OA rose by a robust 88% during 2007-2016, while the number on OA not focused on orthopedic procedures grew by 65%. Both of these increases were greater than those for publications on musculoskeletal diseases and joint diseases overall, which were 41% and 51%, respectively. But the absolute number of OA publications was dwarfed by the numbers of those in the other search categories. For example, the number of publications on OA without an orthopedic surgery thrust was 985 in 2007, compared with 7,204 on joint diseases overall.

Among the striking findings of the investigators’ study of the medical literature was the disconnect between the amount of attention devoted to some of the joint-specific manifestations of OA and the actual prevalence of these conditions in the population. For example, the prevalence of hand OA in people living with OA was 52% according to the 2009 Survey on Living with Chronic Diseases in Canada, conducted by Statistics Canada, yet only 6.5% of the publications on OA in 2016 were devoted to hand/thumb OA. Similarly, the prevalence of spine OA was 52% among Canadians with OA, but only 4.3% of OA publications in 2016 focused on that topic. And while the number of publications devoted to elbow OA soared by a seemingly impressive 233% during the study period, the actual numbers were 3 publications in 2007 and 10 in 2016.

“Also, the average number of affected joints in people with osteoarthritis is four. Yet very, very few papers are about multijoint osteoarthritis. And when they do talk about multijoint osteoarthritis, they’re still only talking about hand/hip/knee. So we’re missing the bigger picture of osteoarthritis as a multijoint disease. We’re missing the spine, largely, as a part of osteoarthritis, and we’re missing the peripheral joints,” she said.

Dr. Badley reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Badley EM et al. Osteoarthritis Cartilage. 2019 Apr;27(Suppl 1):S278, Abstract 393.

TORONTO – Oral methotrexate therapy was associated with significant reductions in knee osteoarthritis pain, stiffness, and functional impairment, compared with placebo at 6 months in the randomized, double-blind PROMOTE trial, Philip G. Conaghan, MD, PhD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

There is, however, an asterisk attached to these findings. “Despite a moderate standard effect size, the treatment effect was smaller than some of the thresholds for what is considered clinically meaningful,” he noted at the meeting sponsored by the Osteoarthritis Research Society International.

That being said, the rheumatologist is convinced further investigation of methotrexate in osteoarthritis is warranted.

“I have to say that, unlike our earlier hydroxychloroquine trial, which was robustly negative with nothing more to say, I think there is a signal in this study. I need to understand the results of this trial better to understand if there is a subgroup we could treat with methotrexate. It’s a cheap drug, it’s readily available, and we’ve got a lot of experience with it,” noted Dr. Conaghan, professor of musculoskeletal medicine at the University of Leeds (England) and director of the Leeds Institute of Rheumatic and Musculoskeletal Medicine.

The rationale for the 15-center PROMOTE trial is that synovitis is common in OA. Synovitis is associated with pain, methotrexate is the gold-standard treatment for synovitis in inflammatory forms of arthritis, and current treatments for OA are, to say the least, severely limited. Also, an earlier 30-patient, open-label pilot study of methotrexate in patients with painful knee OA conducted by Dr. Conaghan and coworkers suggested the drug was promising (Rheumatology [Oxford]. 2013 May;52[5]:888-92).

PROMOTE included 134 patients with symptomatic and radiographic knee OA who were randomized in double-blind fashion to 6 months of oral methotrexate at 10 mg titrated to a target dose of 25 mg/week or to placebo. All patients also received usual care with oral NSAIDs and/or acetaminophen. Their mean baseline knee pain on a 0-10 numeric rating scale was 6.6.

The primary endpoint, assessed at 6 months, was the difference between the two study arms in average knee pain during the previous week on a 0-10 scale. The score was 5.1 in the methotrexate group and 6.2 in the placebo arm, for a baseline-adjusted treatment difference of 0.83 points, which works out to a standard effect size of 0.36. When the data were reanalyzed after excluding the 15 patients who missed more than four doses of medication within any 3-month period, the between-group difference in pain scores increased to 0.95 points in favor of the methotrexate group.

A significant difference in favor of the methotrexate group was documented in the OARSI-OMERACT response rate at 6 months: 45% in the methotrexate group and 26% in the controls. Some secondary endpoints were positive as well, with statistically significant differences seen at 6 months in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness, WOMAC physical function, and several other endpoints. But there were no significant differences in WOMAC pain, SF-12 physical component or SF-12 mental component scores, or in an OA quality of life measure.

The mean dose of methotrexate used in the study was about 17 mg/week. Dr. Conaghan said that if he could do the trial over again, he would have used subcutaneous methotrexate.

“It’s a more reliable way of getting a dose into people and probably of getting a slightly higher dose into people. In the rheumatoid arthritis world, we use a lot more subcutaneous methotrexate now than we did 10 years ago because it gets around a lot of the minor side effects and helps compliance,” he said.

One audience member suggested that one potentially useful way to zero in on a subgroup of knee OA patients likely to derive the most benefit from methotrexate would be to have screened potential study participants for comorbid fibromyalgia and exclude those with the disorder. Dr. Conaghan replied that the PROMOTE investigators did gather data on participants’ pain at sites other than the knee. That data can be used to identify those at increased likelihood of fibromyalgia, and he agreed that’s worth looking into.

Dr. Conaghan reported having no financial conflicts regarding PROMOTE, which was funded by the U.K. National Institute for Health Research and Versus Arthritis.

[email protected]

SOURCE: Conaghan PG et al. OARSI 2019, Abstract 86.

TORONTO – Oral methotrexate therapy was associated with significant reductions in knee osteoarthritis pain, stiffness, and functional impairment, compared with placebo at 6 months in the randomized, double-blind PROMOTE trial, Philip G. Conaghan, MD, PhD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

There is, however, an asterisk attached to these findings. “Despite a moderate standard effect size, the treatment effect was smaller than some of the thresholds for what is considered clinically meaningful,” he noted at the meeting sponsored by the Osteoarthritis Research Society International.

That being said, the rheumatologist is convinced further investigation of methotrexate in osteoarthritis is warranted.

“I have to say that, unlike our earlier hydroxychloroquine trial, which was robustly negative with nothing more to say, I think there is a signal in this study. I need to understand the results of this trial better to understand if there is a subgroup we could treat with methotrexate. It’s a cheap drug, it’s readily available, and we’ve got a lot of experience with it,” noted Dr. Conaghan, professor of musculoskeletal medicine at the University of Leeds (England) and director of the Leeds Institute of Rheumatic and Musculoskeletal Medicine.

The rationale for the 15-center PROMOTE trial is that synovitis is common in OA. Synovitis is associated with pain, methotrexate is the gold-standard treatment for synovitis in inflammatory forms of arthritis, and current treatments for OA are, to say the least, severely limited. Also, an earlier 30-patient, open-label pilot study of methotrexate in patients with painful knee OA conducted by Dr. Conaghan and coworkers suggested the drug was promising (Rheumatology [Oxford]. 2013 May;52[5]:888-92).

PROMOTE included 134 patients with symptomatic and radiographic knee OA who were randomized in double-blind fashion to 6 months of oral methotrexate at 10 mg titrated to a target dose of 25 mg/week or to placebo. All patients also received usual care with oral NSAIDs and/or acetaminophen. Their mean baseline knee pain on a 0-10 numeric rating scale was 6.6.

The primary endpoint, assessed at 6 months, was the difference between the two study arms in average knee pain during the previous week on a 0-10 scale. The score was 5.1 in the methotrexate group and 6.2 in the placebo arm, for a baseline-adjusted treatment difference of 0.83 points, which works out to a standard effect size of 0.36. When the data were reanalyzed after excluding the 15 patients who missed more than four doses of medication within any 3-month period, the between-group difference in pain scores increased to 0.95 points in favor of the methotrexate group.

A significant difference in favor of the methotrexate group was documented in the OARSI-OMERACT response rate at 6 months: 45% in the methotrexate group and 26% in the controls. Some secondary endpoints were positive as well, with statistically significant differences seen at 6 months in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness, WOMAC physical function, and several other endpoints. But there were no significant differences in WOMAC pain, SF-12 physical component or SF-12 mental component scores, or in an OA quality of life measure.

The mean dose of methotrexate used in the study was about 17 mg/week. Dr. Conaghan said that if he could do the trial over again, he would have used subcutaneous methotrexate.

“It’s a more reliable way of getting a dose into people and probably of getting a slightly higher dose into people. In the rheumatoid arthritis world, we use a lot more subcutaneous methotrexate now than we did 10 years ago because it gets around a lot of the minor side effects and helps compliance,” he said.

One audience member suggested that one potentially useful way to zero in on a subgroup of knee OA patients likely to derive the most benefit from methotrexate would be to have screened potential study participants for comorbid fibromyalgia and exclude those with the disorder. Dr. Conaghan replied that the PROMOTE investigators did gather data on participants’ pain at sites other than the knee. That data can be used to identify those at increased likelihood of fibromyalgia, and he agreed that’s worth looking into.

Dr. Conaghan reported having no financial conflicts regarding PROMOTE, which was funded by the U.K. National Institute for Health Research and Versus Arthritis.

[email protected]

SOURCE: Conaghan PG et al. OARSI 2019, Abstract 86.

TORONTO – Oral methotrexate therapy was associated with significant reductions in knee osteoarthritis pain, stiffness, and functional impairment, compared with placebo at 6 months in the randomized, double-blind PROMOTE trial, Philip G. Conaghan, MD, PhD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

There is, however, an asterisk attached to these findings. “Despite a moderate standard effect size, the treatment effect was smaller than some of the thresholds for what is considered clinically meaningful,” he noted at the meeting sponsored by the Osteoarthritis Research Society International.

That being said, the rheumatologist is convinced further investigation of methotrexate in osteoarthritis is warranted.

“I have to say that, unlike our earlier hydroxychloroquine trial, which was robustly negative with nothing more to say, I think there is a signal in this study. I need to understand the results of this trial better to understand if there is a subgroup we could treat with methotrexate. It’s a cheap drug, it’s readily available, and we’ve got a lot of experience with it,” noted Dr. Conaghan, professor of musculoskeletal medicine at the University of Leeds (England) and director of the Leeds Institute of Rheumatic and Musculoskeletal Medicine.

The rationale for the 15-center PROMOTE trial is that synovitis is common in OA. Synovitis is associated with pain, methotrexate is the gold-standard treatment for synovitis in inflammatory forms of arthritis, and current treatments for OA are, to say the least, severely limited. Also, an earlier 30-patient, open-label pilot study of methotrexate in patients with painful knee OA conducted by Dr. Conaghan and coworkers suggested the drug was promising (Rheumatology [Oxford]. 2013 May;52[5]:888-92).

PROMOTE included 134 patients with symptomatic and radiographic knee OA who were randomized in double-blind fashion to 6 months of oral methotrexate at 10 mg titrated to a target dose of 25 mg/week or to placebo. All patients also received usual care with oral NSAIDs and/or acetaminophen. Their mean baseline knee pain on a 0-10 numeric rating scale was 6.6.

The primary endpoint, assessed at 6 months, was the difference between the two study arms in average knee pain during the previous week on a 0-10 scale. The score was 5.1 in the methotrexate group and 6.2 in the placebo arm, for a baseline-adjusted treatment difference of 0.83 points, which works out to a standard effect size of 0.36. When the data were reanalyzed after excluding the 15 patients who missed more than four doses of medication within any 3-month period, the between-group difference in pain scores increased to 0.95 points in favor of the methotrexate group.

A significant difference in favor of the methotrexate group was documented in the OARSI-OMERACT response rate at 6 months: 45% in the methotrexate group and 26% in the controls. Some secondary endpoints were positive as well, with statistically significant differences seen at 6 months in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness, WOMAC physical function, and several other endpoints. But there were no significant differences in WOMAC pain, SF-12 physical component or SF-12 mental component scores, or in an OA quality of life measure.

The mean dose of methotrexate used in the study was about 17 mg/week. Dr. Conaghan said that if he could do the trial over again, he would have used subcutaneous methotrexate.

“It’s a more reliable way of getting a dose into people and probably of getting a slightly higher dose into people. In the rheumatoid arthritis world, we use a lot more subcutaneous methotrexate now than we did 10 years ago because it gets around a lot of the minor side effects and helps compliance,” he said.

One audience member suggested that one potentially useful way to zero in on a subgroup of knee OA patients likely to derive the most benefit from methotrexate would be to have screened potential study participants for comorbid fibromyalgia and exclude those with the disorder. Dr. Conaghan replied that the PROMOTE investigators did gather data on participants’ pain at sites other than the knee. That data can be used to identify those at increased likelihood of fibromyalgia, and he agreed that’s worth looking into.

Dr. Conaghan reported having no financial conflicts regarding PROMOTE, which was funded by the U.K. National Institute for Health Research and Versus Arthritis.

[email protected]

SOURCE: Conaghan PG et al. OARSI 2019, Abstract 86.

TORONTO – Patients with osteoarthritis often want to know if their debilitating disease is likely to be passed on to their children. Karin Magnusson, PhD, believes she can answer that question based upon an analysis of two large Nordic studies.

Bruce Jancin/MDedge News

“OA in the mother, but not in the father, increases the risk of surgical and clinically defined hip, knee, and hand OA in the offspring, and particularly in daughters,” she reported at the OARSI 2019 World Congress.

Dr. Magnusson, an epidemiologist at Lund (Sweden) University, and her coinvestigators, turned to the Musculoskeletal Pain in Ullensaker Study (MUST) of 630 individuals aged 40-79 with rheumatologist-diagnosed hand, hip, or knee OA by American College of Rheumatology clinical criteria and their offspring, as well as the Nor-Twin OA Study of 7,184 twins, aged 30-75, and their children. Linkage with a national registry that records virtually all joint arthroplasties performed in Norway enabled the investigators to identify which subjects in the two studies had joint surgery for OA, she explained at the meeting, sponsored by the Osteoarthritis Research Society International.

The main outcome in this analysis was the relative risk of hip, knee, or hand OA in the sons and daughters of families in which a parent had OA at those sites, compared with the rate when neither parent had OA. The key finding: If the mother had OA, her daughters had a 13% increased risk of OA in MUST and a 44% increased risk in the Nor-Twin OA Study when compared with daughters of women without OA. In contrast, the sons of a mother with OA had no significant increase in risk of OA. And when OA was present in the father, there was no increased risk of OA at any site in his daughters or sons.

“The implication is the heredity of OA is linked to maternal genes and/or maternal-specific factors, such as the fetal environment,” according to Dr. Magnusson.

And for clinical practice, the implication is that it’s important to ask about family history of OA, and in which parent, to better predict future risk of disease transmission to the children, she added.

These Norwegian study results open the door to exploration of the possible role of mitochondrial DNA in familial clustering of OA, since mitochondrial DNA is inherited only from the mother, Dr. Magnusson noted.

David T. Felson, MD, rose from the audience to say, “I’m a little bit worried” about the fact that when he and other Framingham Heart Study investigators looked specifically for possible mother/daughter, mother/son, father/daughter, and father/son associations for knee and hip OA, “we really didn’t find any.

“You can go through all of the explanations that you want about maternal inheritance, but I’m not sure that’s the best explanation. It might just be that what’s going on here is you’re seeing guys who are relatively young and who got their OA through injury or sports, which is fairly common in young men, and not through inheritance,” said Dr. Felson, professor of medicine and epidemiology at Boston University.

So a third observational study in an independent cohort might be needed as a tie breaker regarding the issue of OA inheritance.

Dr. Magnusson reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Magnusson K et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S47, Abstract 33

TORONTO – Patients with osteoarthritis often want to know if their debilitating disease is likely to be passed on to their children. Karin Magnusson, PhD, believes she can answer that question based upon an analysis of two large Nordic studies.

Bruce Jancin/MDedge News

“OA in the mother, but not in the father, increases the risk of surgical and clinically defined hip, knee, and hand OA in the offspring, and particularly in daughters,” she reported at the OARSI 2019 World Congress.

Dr. Magnusson, an epidemiologist at Lund (Sweden) University, and her coinvestigators, turned to the Musculoskeletal Pain in Ullensaker Study (MUST) of 630 individuals aged 40-79 with rheumatologist-diagnosed hand, hip, or knee OA by American College of Rheumatology clinical criteria and their offspring, as well as the Nor-Twin OA Study of 7,184 twins, aged 30-75, and their children. Linkage with a national registry that records virtually all joint arthroplasties performed in Norway enabled the investigators to identify which subjects in the two studies had joint surgery for OA, she explained at the meeting, sponsored by the Osteoarthritis Research Society International.

The main outcome in this analysis was the relative risk of hip, knee, or hand OA in the sons and daughters of families in which a parent had OA at those sites, compared with the rate when neither parent had OA. The key finding: If the mother had OA, her daughters had a 13% increased risk of OA in MUST and a 44% increased risk in the Nor-Twin OA Study when compared with daughters of women without OA. In contrast, the sons of a mother with OA had no significant increase in risk of OA. And when OA was present in the father, there was no increased risk of OA at any site in his daughters or sons.

“The implication is the heredity of OA is linked to maternal genes and/or maternal-specific factors, such as the fetal environment,” according to Dr. Magnusson.

And for clinical practice, the implication is that it’s important to ask about family history of OA, and in which parent, to better predict future risk of disease transmission to the children, she added.

These Norwegian study results open the door to exploration of the possible role of mitochondrial DNA in familial clustering of OA, since mitochondrial DNA is inherited only from the mother, Dr. Magnusson noted.

David T. Felson, MD, rose from the audience to say, “I’m a little bit worried” about the fact that when he and other Framingham Heart Study investigators looked specifically for possible mother/daughter, mother/son, father/daughter, and father/son associations for knee and hip OA, “we really didn’t find any.

“You can go through all of the explanations that you want about maternal inheritance, but I’m not sure that’s the best explanation. It might just be that what’s going on here is you’re seeing guys who are relatively young and who got their OA through injury or sports, which is fairly common in young men, and not through inheritance,” said Dr. Felson, professor of medicine and epidemiology at Boston University.

So a third observational study in an independent cohort might be needed as a tie breaker regarding the issue of OA inheritance.

Dr. Magnusson reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Magnusson K et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S47, Abstract 33

TORONTO – Patients with osteoarthritis often want to know if their debilitating disease is likely to be passed on to their children. Karin Magnusson, PhD, believes she can answer that question based upon an analysis of two large Nordic studies.

Bruce Jancin/MDedge News

“OA in the mother, but not in the father, increases the risk of surgical and clinically defined hip, knee, and hand OA in the offspring, and particularly in daughters,” she reported at the OARSI 2019 World Congress.

Dr. Magnusson, an epidemiologist at Lund (Sweden) University, and her coinvestigators, turned to the Musculoskeletal Pain in Ullensaker Study (MUST) of 630 individuals aged 40-79 with rheumatologist-diagnosed hand, hip, or knee OA by American College of Rheumatology clinical criteria and their offspring, as well as the Nor-Twin OA Study of 7,184 twins, aged 30-75, and their children. Linkage with a national registry that records virtually all joint arthroplasties performed in Norway enabled the investigators to identify which subjects in the two studies had joint surgery for OA, she explained at the meeting, sponsored by the Osteoarthritis Research Society International.

The main outcome in this analysis was the relative risk of hip, knee, or hand OA in the sons and daughters of families in which a parent had OA at those sites, compared with the rate when neither parent had OA. The key finding: If the mother had OA, her daughters had a 13% increased risk of OA in MUST and a 44% increased risk in the Nor-Twin OA Study when compared with daughters of women without OA. In contrast, the sons of a mother with OA had no significant increase in risk of OA. And when OA was present in the father, there was no increased risk of OA at any site in his daughters or sons.

“The implication is the heredity of OA is linked to maternal genes and/or maternal-specific factors, such as the fetal environment,” according to Dr. Magnusson.

And for clinical practice, the implication is that it’s important to ask about family history of OA, and in which parent, to better predict future risk of disease transmission to the children, she added.

These Norwegian study results open the door to exploration of the possible role of mitochondrial DNA in familial clustering of OA, since mitochondrial DNA is inherited only from the mother, Dr. Magnusson noted.

David T. Felson, MD, rose from the audience to say, “I’m a little bit worried” about the fact that when he and other Framingham Heart Study investigators looked specifically for possible mother/daughter, mother/son, father/daughter, and father/son associations for knee and hip OA, “we really didn’t find any.

“You can go through all of the explanations that you want about maternal inheritance, but I’m not sure that’s the best explanation. It might just be that what’s going on here is you’re seeing guys who are relatively young and who got their OA through injury or sports, which is fairly common in young men, and not through inheritance,” said Dr. Felson, professor of medicine and epidemiology at Boston University.

So a third observational study in an independent cohort might be needed as a tie breaker regarding the issue of OA inheritance.

Dr. Magnusson reported having no financial conflicts regarding her study, conducted free of commercial support.

[email protected]

SOURCE: Magnusson K et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S47, Abstract 33

TORONTO – Tanezumab, a novel investigational nerve growth factor inhibitor, not only proved effective for the treatment of refractory pain in knee and hip osteoarthritis but was also notably rapidly acting, according to a secondary analysis of a phase 3 randomized trial.

Bruce Jancin/MDedge News

“The onset is relatively quick. It’s a monoclonal antibody, so it doesn’t work overnight, but by 3-5 days you see a significant difference,” Thomas J. Schnitzer, MD, PhD, reported at the OARSI 2019 World Congress.

He had previously presented the primary outcomes of this 696-patient, phase 3, randomized trial at the 2018 annual meeting of the American College of Rheumatology. At OARSI 2019, the rheumatologist presented new data focusing on the speed and durability of the pain relief provided by tanezumab, a humanized monoclonal antibody designed to help keep pain signals produced in the periphery from reaching the CNS.

The double-blind trial included U.S. patients with an average 9.3-year disease duration who were randomized to either two 2.5-mg subcutaneous injections of the nerve growth factor inhibitor 8 weeks apart, a 2.5-mg dose followed 8 weeks later by a 5-mg dose, or two placebo injections. Eighty-five percent of subjects had knee OA, and the rest had hip OA. The patients had fairly severe pain, with average baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores of 7.1-7.4. Notably, all study participants had to have a documented history of previous failure to respond to at least three pain relievers: acetaminophen, oral NSAIDs, and tramadol or opioids, according to Dr. Schnitzer, a rheumatologist who is professor of physical medicine and rehabilitation, anesthesiology, and medicine at Northwestern University in Chicago.

As previously reported, the co–primary endpoint of change from baseline to week 16 in WOMAC pain was –3.22 points with the 2.5-mg tanezumab regimen and –3.45 with the 2.5/5–mg strategy, both significantly better than the 2.56-point improvement with placebo. Improvement in WOMAC physical function followed suit, he said at the meeting sponsored by the Osteoarthritis Research Society International.

Assessments were made at office visits every 2 weeks during the study. By the first visit at week 2, tanezumab was significantly better than placebo on both WOMAC measures, an advantage maintained for the rest of the 16 weeks. Pain relief in the tanezumab-treated groups was maximum at weeks 4 and 12; that is, 4 weeks following the first and second injections.

“This suggests that there’s an immediate effect of the antibody, which then tends to wane as the antibody begins to get cleared,” Dr. Schnitzer observed.

Study participants kept a structured daily pain diary, which enabled investigators to zero in on the timing of pain relief. Statistically significant separation from placebo was documented by day 3 in one group on tanezumab and by day 5 in the other.

An increased rate of rapidly progressive OA was a concern years ago in earlier studies of a now-abandoned intravenous formulation of tanezumab. However, in the phase 3 trial of the subcutaneous humanized monoclonal antibody, rapidly progressive OA occurred in only six patients, or 1.3%, during the 24-week safety follow-up period. Interestingly, the phenomenon was not dose related, as five of the six cases occurred in patients on the twin 2.5-mg regimen, and only one in the 2.5/5-mg group. No cases of osteonecrosis occurred in the trial.

One audience member rose to say she and her fellow rheumatologists are very excited about the prospect of possible access to a novel and more effective OA therapy. But she took issue with the trial’s reliance on WOMAC pain and physical function scores as primary endpoints, noting that OARSI experts have developed and validated several more comprehensive and globally informative assessment tools. Dr. Schnitzer readily agreed. The investigators utilized WOMAC pain and physical function because that’s what the U.S. and European regulatory agencies insist upon, he explained.

Clinicians should stay tuned because the results of much larger, longer-term phase 3 trials of tanezumab are due to be presented soon, he added.

Dr. Schnitzer reported serving as a consultant to Pfizer and Eli Lilly, which are jointly developing tanezumab and sponsored the trial, as well as to a handful of other pharmaceutical companies.

[email protected]

SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.

TORONTO – Tanezumab, a novel investigational nerve growth factor inhibitor, not only proved effective for the treatment of refractory pain in knee and hip osteoarthritis but was also notably rapidly acting, according to a secondary analysis of a phase 3 randomized trial.

Bruce Jancin/MDedge News

“The onset is relatively quick. It’s a monoclonal antibody, so it doesn’t work overnight, but by 3-5 days you see a significant difference,” Thomas J. Schnitzer, MD, PhD, reported at the OARSI 2019 World Congress.

He had previously presented the primary outcomes of this 696-patient, phase 3, randomized trial at the 2018 annual meeting of the American College of Rheumatology. At OARSI 2019, the rheumatologist presented new data focusing on the speed and durability of the pain relief provided by tanezumab, a humanized monoclonal antibody designed to help keep pain signals produced in the periphery from reaching the CNS.

The double-blind trial included U.S. patients with an average 9.3-year disease duration who were randomized to either two 2.5-mg subcutaneous injections of the nerve growth factor inhibitor 8 weeks apart, a 2.5-mg dose followed 8 weeks later by a 5-mg dose, or two placebo injections. Eighty-five percent of subjects had knee OA, and the rest had hip OA. The patients had fairly severe pain, with average baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores of 7.1-7.4. Notably, all study participants had to have a documented history of previous failure to respond to at least three pain relievers: acetaminophen, oral NSAIDs, and tramadol or opioids, according to Dr. Schnitzer, a rheumatologist who is professor of physical medicine and rehabilitation, anesthesiology, and medicine at Northwestern University in Chicago.

As previously reported, the co–primary endpoint of change from baseline to week 16 in WOMAC pain was –3.22 points with the 2.5-mg tanezumab regimen and –3.45 with the 2.5/5–mg strategy, both significantly better than the 2.56-point improvement with placebo. Improvement in WOMAC physical function followed suit, he said at the meeting sponsored by the Osteoarthritis Research Society International.

Assessments were made at office visits every 2 weeks during the study. By the first visit at week 2, tanezumab was significantly better than placebo on both WOMAC measures, an advantage maintained for the rest of the 16 weeks. Pain relief in the tanezumab-treated groups was maximum at weeks 4 and 12; that is, 4 weeks following the first and second injections.

“This suggests that there’s an immediate effect of the antibody, which then tends to wane as the antibody begins to get cleared,” Dr. Schnitzer observed.

Study participants kept a structured daily pain diary, which enabled investigators to zero in on the timing of pain relief. Statistically significant separation from placebo was documented by day 3 in one group on tanezumab and by day 5 in the other.

An increased rate of rapidly progressive OA was a concern years ago in earlier studies of a now-abandoned intravenous formulation of tanezumab. However, in the phase 3 trial of the subcutaneous humanized monoclonal antibody, rapidly progressive OA occurred in only six patients, or 1.3%, during the 24-week safety follow-up period. Interestingly, the phenomenon was not dose related, as five of the six cases occurred in patients on the twin 2.5-mg regimen, and only one in the 2.5/5-mg group. No cases of osteonecrosis occurred in the trial.

One audience member rose to say she and her fellow rheumatologists are very excited about the prospect of possible access to a novel and more effective OA therapy. But she took issue with the trial’s reliance on WOMAC pain and physical function scores as primary endpoints, noting that OARSI experts have developed and validated several more comprehensive and globally informative assessment tools. Dr. Schnitzer readily agreed. The investigators utilized WOMAC pain and physical function because that’s what the U.S. and European regulatory agencies insist upon, he explained.

Clinicians should stay tuned because the results of much larger, longer-term phase 3 trials of tanezumab are due to be presented soon, he added.

Dr. Schnitzer reported serving as a consultant to Pfizer and Eli Lilly, which are jointly developing tanezumab and sponsored the trial, as well as to a handful of other pharmaceutical companies.

[email protected]

SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.

TORONTO – Tanezumab, a novel investigational nerve growth factor inhibitor, not only proved effective for the treatment of refractory pain in knee and hip osteoarthritis but was also notably rapidly acting, according to a secondary analysis of a phase 3 randomized trial.

Bruce Jancin/MDedge News

“The onset is relatively quick. It’s a monoclonal antibody, so it doesn’t work overnight, but by 3-5 days you see a significant difference,” Thomas J. Schnitzer, MD, PhD, reported at the OARSI 2019 World Congress.

He had previously presented the primary outcomes of this 696-patient, phase 3, randomized trial at the 2018 annual meeting of the American College of Rheumatology. At OARSI 2019, the rheumatologist presented new data focusing on the speed and durability of the pain relief provided by tanezumab, a humanized monoclonal antibody designed to help keep pain signals produced in the periphery from reaching the CNS.

The double-blind trial included U.S. patients with an average 9.3-year disease duration who were randomized to either two 2.5-mg subcutaneous injections of the nerve growth factor inhibitor 8 weeks apart, a 2.5-mg dose followed 8 weeks later by a 5-mg dose, or two placebo injections. Eighty-five percent of subjects had knee OA, and the rest had hip OA. The patients had fairly severe pain, with average baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores of 7.1-7.4. Notably, all study participants had to have a documented history of previous failure to respond to at least three pain relievers: acetaminophen, oral NSAIDs, and tramadol or opioids, according to Dr. Schnitzer, a rheumatologist who is professor of physical medicine and rehabilitation, anesthesiology, and medicine at Northwestern University in Chicago.

As previously reported, the co–primary endpoint of change from baseline to week 16 in WOMAC pain was –3.22 points with the 2.5-mg tanezumab regimen and –3.45 with the 2.5/5–mg strategy, both significantly better than the 2.56-point improvement with placebo. Improvement in WOMAC physical function followed suit, he said at the meeting sponsored by the Osteoarthritis Research Society International.

Assessments were made at office visits every 2 weeks during the study. By the first visit at week 2, tanezumab was significantly better than placebo on both WOMAC measures, an advantage maintained for the rest of the 16 weeks. Pain relief in the tanezumab-treated groups was maximum at weeks 4 and 12; that is, 4 weeks following the first and second injections.

“This suggests that there’s an immediate effect of the antibody, which then tends to wane as the antibody begins to get cleared,” Dr. Schnitzer observed.

Study participants kept a structured daily pain diary, which enabled investigators to zero in on the timing of pain relief. Statistically significant separation from placebo was documented by day 3 in one group on tanezumab and by day 5 in the other.

An increased rate of rapidly progressive OA was a concern years ago in earlier studies of a now-abandoned intravenous formulation of tanezumab. However, in the phase 3 trial of the subcutaneous humanized monoclonal antibody, rapidly progressive OA occurred in only six patients, or 1.3%, during the 24-week safety follow-up period. Interestingly, the phenomenon was not dose related, as five of the six cases occurred in patients on the twin 2.5-mg regimen, and only one in the 2.5/5-mg group. No cases of osteonecrosis occurred in the trial.

One audience member rose to say she and her fellow rheumatologists are very excited about the prospect of possible access to a novel and more effective OA therapy. But she took issue with the trial’s reliance on WOMAC pain and physical function scores as primary endpoints, noting that OARSI experts have developed and validated several more comprehensive and globally informative assessment tools. Dr. Schnitzer readily agreed. The investigators utilized WOMAC pain and physical function because that’s what the U.S. and European regulatory agencies insist upon, he explained.

Clinicians should stay tuned because the results of much larger, longer-term phase 3 trials of tanezumab are due to be presented soon, he added.

Dr. Schnitzer reported serving as a consultant to Pfizer and Eli Lilly, which are jointly developing tanezumab and sponsored the trial, as well as to a handful of other pharmaceutical companies.

[email protected]

SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.

TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.

A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.

Bruce Jancin/MDedge News

About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.

There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.

Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.

She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.

[email protected]

TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.

A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.

Bruce Jancin/MDedge News

About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.

There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.

Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.

She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.

[email protected]

TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.

A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.

Bruce Jancin/MDedge News

About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.

There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.

Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.

She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.

[email protected]

TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.

Bruce Jancin/MDedge News

Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.

A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.

The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.

The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.

“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.

For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.

Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.

Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.

The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.

[email protected]

TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.

Bruce Jancin/MDedge News

Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.

A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.

The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.

The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.

“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.

For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.

Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.

Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.

The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.

[email protected]

TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.

Bruce Jancin/MDedge News

Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.

A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.

The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.

The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.

“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.

For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.

Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.

Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.

The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.

[email protected]

TORONTO – The disease burden of osteoarthritis at the time of the first visit to a rheumatologist is similar to that of a new rheumatoid arthritis patient; the big difference between the two diseases is that a year later the disease burden of RA is significantly diminished, while it remains unchanged over time in OA patients, Theodore Pincus, MD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

These divergent trajectories of disease burden, as measured using a validated patient self-assessment instrument, reflect the far superior and more numerous therapies available for treatment of RA. It’s an unfortunate disparity, especially given that OA is more than 20 times as prevalent as RA.

But the side-by-side, patient self-reported disease burden data presented by Dr. Pincus also underscored another point: “The severity of disease burden in OA to the patient appears to be underrated by the medical community, general public, and even patients,” he said at the meeting sponsored by the Osteoarthritis Research Society International.

Dr. Pincus, a pioneer in outcomes assessment in rheumatology, is credited with codeveloping the RAPID 3 (Routine Assessment of Patient Index Data 3) score, widely utilized by rheumatologists as part of routine care in clinical practice (Bull NYU Hosp Jt Dis. 2009;67[2]:211-25).

At OARSI 2019, he presented results of a longitudinal study of disease burden over the course of 2 years in 101 patients with OA and 175 with RA who completed the Multidimensional Health Assessment Questionnaire (MDHAQ) and RAPID 3 in the waiting room before their first and all subsequent office visits with a rheumatologist. The MDHAQ, another self-assessment tool codeveloped by Dr. Pincus, is a two-page questionnaire that includes scores for pain, physical function in 10 activities, fatigue, and a self-reported painful joint count.

At the first visit with a rheumatologist, the mean MDHAQ/RAPID 3 score on a 0-30 scale was 11.9 in the OA group and 13.7 in the RA patients, a difference small enough that Dr. Pincus dismissed it as not clinically significant. After 1 year, the mean score was 11.5 in the OA group, and 2 years later it was 11.9, identical to the OA patients’ score back at their first visit. Meanwhile, the RA patients improved from 13.7 at baseline to 10.9 at 1 year and 9.0 at 2 years, according to Dr. Pincus, professor of rheumatology at Rush Medical College, Chicago.

The between-group differences over time in pain and physical function were particularly telling. Pain on a 0-10 scale stuttered from 5.0 at first visit in the OA group to 4.9 at 1 year and 4.7 at 2 years, while the RA group registered much greater improvement, going from a mean of 5.5 at first visit to 4.3 at 1 year and 3.6 at 2 years. Meanwhile, physical function worsened over time in the OA group while improving in the RA group from 0.78 at first visit to 0.66 at 1 year and 0.53 at 2 years, he noted.

Dr. Pincus reported having no financial conflicts regarding this study.

[email protected]

TORONTO – The disease burden of osteoarthritis at the time of the first visit to a rheumatologist is similar to that of a new rheumatoid arthritis patient; the big difference between the two diseases is that a year later the disease burden of RA is significantly diminished, while it remains unchanged over time in OA patients, Theodore Pincus, MD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

These divergent trajectories of disease burden, as measured using a validated patient self-assessment instrument, reflect the far superior and more numerous therapies available for treatment of RA. It’s an unfortunate disparity, especially given that OA is more than 20 times as prevalent as RA.

But the side-by-side, patient self-reported disease burden data presented by Dr. Pincus also underscored another point: “The severity of disease burden in OA to the patient appears to be underrated by the medical community, general public, and even patients,” he said at the meeting sponsored by the Osteoarthritis Research Society International.

Dr. Pincus, a pioneer in outcomes assessment in rheumatology, is credited with codeveloping the RAPID 3 (Routine Assessment of Patient Index Data 3) score, widely utilized by rheumatologists as part of routine care in clinical practice (Bull NYU Hosp Jt Dis. 2009;67[2]:211-25).

At OARSI 2019, he presented results of a longitudinal study of disease burden over the course of 2 years in 101 patients with OA and 175 with RA who completed the Multidimensional Health Assessment Questionnaire (MDHAQ) and RAPID 3 in the waiting room before their first and all subsequent office visits with a rheumatologist. The MDHAQ, another self-assessment tool codeveloped by Dr. Pincus, is a two-page questionnaire that includes scores for pain, physical function in 10 activities, fatigue, and a self-reported painful joint count.

At the first visit with a rheumatologist, the mean MDHAQ/RAPID 3 score on a 0-30 scale was 11.9 in the OA group and 13.7 in the RA patients, a difference small enough that Dr. Pincus dismissed it as not clinically significant. After 1 year, the mean score was 11.5 in the OA group, and 2 years later it was 11.9, identical to the OA patients’ score back at their first visit. Meanwhile, the RA patients improved from 13.7 at baseline to 10.9 at 1 year and 9.0 at 2 years, according to Dr. Pincus, professor of rheumatology at Rush Medical College, Chicago.

The between-group differences over time in pain and physical function were particularly telling. Pain on a 0-10 scale stuttered from 5.0 at first visit in the OA group to 4.9 at 1 year and 4.7 at 2 years, while the RA group registered much greater improvement, going from a mean of 5.5 at first visit to 4.3 at 1 year and 3.6 at 2 years. Meanwhile, physical function worsened over time in the OA group while improving in the RA group from 0.78 at first visit to 0.66 at 1 year and 0.53 at 2 years, he noted.

Dr. Pincus reported having no financial conflicts regarding this study.

[email protected]

TORONTO – The disease burden of osteoarthritis at the time of the first visit to a rheumatologist is similar to that of a new rheumatoid arthritis patient; the big difference between the two diseases is that a year later the disease burden of RA is significantly diminished, while it remains unchanged over time in OA patients, Theodore Pincus, MD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

These divergent trajectories of disease burden, as measured using a validated patient self-assessment instrument, reflect the far superior and more numerous therapies available for treatment of RA. It’s an unfortunate disparity, especially given that OA is more than 20 times as prevalent as RA.

But the side-by-side, patient self-reported disease burden data presented by Dr. Pincus also underscored another point: “The severity of disease burden in OA to the patient appears to be underrated by the medical community, general public, and even patients,” he said at the meeting sponsored by the Osteoarthritis Research Society International.

Dr. Pincus, a pioneer in outcomes assessment in rheumatology, is credited with codeveloping the RAPID 3 (Routine Assessment of Patient Index Data 3) score, widely utilized by rheumatologists as part of routine care in clinical practice (Bull NYU Hosp Jt Dis. 2009;67[2]:211-25).

At OARSI 2019, he presented results of a longitudinal study of disease burden over the course of 2 years in 101 patients with OA and 175 with RA who completed the Multidimensional Health Assessment Questionnaire (MDHAQ) and RAPID 3 in the waiting room before their first and all subsequent office visits with a rheumatologist. The MDHAQ, another self-assessment tool codeveloped by Dr. Pincus, is a two-page questionnaire that includes scores for pain, physical function in 10 activities, fatigue, and a self-reported painful joint count.

At the first visit with a rheumatologist, the mean MDHAQ/RAPID 3 score on a 0-30 scale was 11.9 in the OA group and 13.7 in the RA patients, a difference small enough that Dr. Pincus dismissed it as not clinically significant. After 1 year, the mean score was 11.5 in the OA group, and 2 years later it was 11.9, identical to the OA patients’ score back at their first visit. Meanwhile, the RA patients improved from 13.7 at baseline to 10.9 at 1 year and 9.0 at 2 years, according to Dr. Pincus, professor of rheumatology at Rush Medical College, Chicago.

The between-group differences over time in pain and physical function were particularly telling. Pain on a 0-10 scale stuttered from 5.0 at first visit in the OA group to 4.9 at 1 year and 4.7 at 2 years, while the RA group registered much greater improvement, going from a mean of 5.5 at first visit to 4.3 at 1 year and 3.6 at 2 years. Meanwhile, physical function worsened over time in the OA group while improving in the RA group from 0.78 at first visit to 0.66 at 1 year and 0.53 at 2 years, he noted.

Dr. Pincus reported having no financial conflicts regarding this study.

[email protected]

TORONTO – As Ontario moved toward bundled payments for services related to orthopedic surgeries for osteoarthritis, procedural volume climbed, average hospital length of stay dropped, and the 30-day postdischarge readmission rate declined modestly. However, emergency department visits shot up by 62%.

Bruce Jancin/MDedge News

And therein lies a key lesson for health policy makers who have embraced bundled payments to reduce rising health care costs, Mayilee Canizares, PhD, observed at the OARSI 2019 World Congress.

In Ontario, with patients discharged sooner and directly to home, there was the negative impact of increased emergency department visits after surgery, Dr. Canizares, of the University Health Network in Toronto, said at OARSI 2019 World Congress, sponsored by the Osteoarthritis Research Society International. “Our findings highlight the importance of coordinating the appropriate support services as well as the need to continue assessing the optimal discharge care plan for osteoarthritis patients undergoing surgery.”

Dr. Canizares’ study of the Ontario-wide experience with orthopedic surgery for osteoarthritis during 2004-2016 received the OARSI 2019 award for the meeting’s top-rated study in clinical epidemiology/health services research.

Using administrative data from Canada’s national health care system, Dr. Canizares and her coinvestigators found that the number of individuals undergoing elective orthopedic surgery for osteoarthritis ballooned from 22,700 in 2004 to 41,900 in 2016, representing an increase from 246 to 381 procedures per 100,000 people. During this time, the mean length of stay declined from about 5 days to just under 3 days, the 30-day readmission rate dropped from 4.2% to 3.4%, and the rate of emergency department visits within 30 days post discharge rose steadily from 8.7% in 2004 to 14.1% in 2016.

Roughly half of the operations were total knee replacements and one-third were hip replacements. The profile of patients undergoing surgery changed little over the course of the 12-year study with the exception that in more recent years patients presented with more comorbidities: Indeed, three or more comorbid conditions were present in 2.9% of the surgical patients in 2004 compared to 4.2% in 2016.

In multivariate logistic regression analyses, patient characteristics didn’t explain the change over time in early readmission or unplanned emergency department visit rates. However, discharge disposition did: By 2014, more patients were being discharged home, and in nearly half of cases that was being done without support.

Dr. Canizares reported having no financial conflicts regarding her study, funded by the Toronto General and Western Hospital Foundation.

[email protected]

SOURCE: Canizares M. OARSI, Abstract 16.

TORONTO – As Ontario moved toward bundled payments for services related to orthopedic surgeries for osteoarthritis, procedural volume climbed, average hospital length of stay dropped, and the 30-day postdischarge readmission rate declined modestly. However, emergency department visits shot up by 62%.

Bruce Jancin/MDedge News

And therein lies a key lesson for health policy makers who have embraced bundled payments to reduce rising health care costs, Mayilee Canizares, PhD, observed at the OARSI 2019 World Congress.

In Ontario, with patients discharged sooner and directly to home, there was the negative impact of increased emergency department visits after surgery, Dr. Canizares, of the University Health Network in Toronto, said at OARSI 2019 World Congress, sponsored by the Osteoarthritis Research Society International. “Our findings highlight the importance of coordinating the appropriate support services as well as the need to continue assessing the optimal discharge care plan for osteoarthritis patients undergoing surgery.”

Dr. Canizares’ study of the Ontario-wide experience with orthopedic surgery for osteoarthritis during 2004-2016 received the OARSI 2019 award for the meeting’s top-rated study in clinical epidemiology/health services research.

Using administrative data from Canada’s national health care system, Dr. Canizares and her coinvestigators found that the number of individuals undergoing elective orthopedic surgery for osteoarthritis ballooned from 22,700 in 2004 to 41,900 in 2016, representing an increase from 246 to 381 procedures per 100,000 people. During this time, the mean length of stay declined from about 5 days to just under 3 days, the 30-day readmission rate dropped from 4.2% to 3.4%, and the rate of emergency department visits within 30 days post discharge rose steadily from 8.7% in 2004 to 14.1% in 2016.

Roughly half of the operations were total knee replacements and one-third were hip replacements. The profile of patients undergoing surgery changed little over the course of the 12-year study with the exception that in more recent years patients presented with more comorbidities: Indeed, three or more comorbid conditions were present in 2.9% of the surgical patients in 2004 compared to 4.2% in 2016.

In multivariate logistic regression analyses, patient characteristics didn’t explain the change over time in early readmission or unplanned emergency department visit rates. However, discharge disposition did: By 2014, more patients were being discharged home, and in nearly half of cases that was being done without support.

Dr. Canizares reported having no financial conflicts regarding her study, funded by the Toronto General and Western Hospital Foundation.

[email protected]

SOURCE: Canizares M. OARSI, Abstract 16.

TORONTO – As Ontario moved toward bundled payments for services related to orthopedic surgeries for osteoarthritis, procedural volume climbed, average hospital length of stay dropped, and the 30-day postdischarge readmission rate declined modestly. However, emergency department visits shot up by 62%.

Bruce Jancin/MDedge News

And therein lies a key lesson for health policy makers who have embraced bundled payments to reduce rising health care costs, Mayilee Canizares, PhD, observed at the OARSI 2019 World Congress.

In Ontario, with patients discharged sooner and directly to home, there was the negative impact of increased emergency department visits after surgery, Dr. Canizares, of the University Health Network in Toronto, said at OARSI 2019 World Congress, sponsored by the Osteoarthritis Research Society International. “Our findings highlight the importance of coordinating the appropriate support services as well as the need to continue assessing the optimal discharge care plan for osteoarthritis patients undergoing surgery.”

Dr. Canizares’ study of the Ontario-wide experience with orthopedic surgery for osteoarthritis during 2004-2016 received the OARSI 2019 award for the meeting’s top-rated study in clinical epidemiology/health services research.

Using administrative data from Canada’s national health care system, Dr. Canizares and her coinvestigators found that the number of individuals undergoing elective orthopedic surgery for osteoarthritis ballooned from 22,700 in 2004 to 41,900 in 2016, representing an increase from 246 to 381 procedures per 100,000 people. During this time, the mean length of stay declined from about 5 days to just under 3 days, the 30-day readmission rate dropped from 4.2% to 3.4%, and the rate of emergency department visits within 30 days post discharge rose steadily from 8.7% in 2004 to 14.1% in 2016.

Roughly half of the operations were total knee replacements and one-third were hip replacements. The profile of patients undergoing surgery changed little over the course of the 12-year study with the exception that in more recent years patients presented with more comorbidities: Indeed, three or more comorbid conditions were present in 2.9% of the surgical patients in 2004 compared to 4.2% in 2016.

In multivariate logistic regression analyses, patient characteristics didn’t explain the change over time in early readmission or unplanned emergency department visit rates. However, discharge disposition did: By 2014, more patients were being discharged home, and in nearly half of cases that was being done without support.

Dr. Canizares reported having no financial conflicts regarding her study, funded by the Toronto General and Western Hospital Foundation.

[email protected]

SOURCE: Canizares M. OARSI, Abstract 16.

TORONTO – Eight physical therapy sessions spread over 4-6 weeks in patients with knee osteoarthritis provided significantly greater and longer-lasting improvements in both pain and function than an intra-articular corticosteroid injection in a randomized, multicenter trial with 12 months of prospective, blinded follow-up, Daniel I. Rhon, DPT, DSc, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Considering the very low utilization rate of physical therapy prior to arthroplasty, perhaps we should more often give it a try before declaring that conservative care has failed and moving on to surgical management,” concluded Dr. Rhon, director of the primary care musculoskeletal research center at Brooke Army Medical Center in San Antonio.

Various studies have shown that close to 50% of patients with knee OA receive one or more intra-articular corticosteroid injections within 5 years prior to undergoing total knee arthroplasty, compared with physical therapy in only about 10% of patients, even though most guidelines rate both as first-line therapies, he noted at the meeting sponsored by the Osteoarthritis Research Society International.

He presented a randomized trial of 156 patients who sought treatment for pain caused by knee OA at army medical center primary care clinics. To his knowledge, this was the first-ever randomized, head-to-head comparison of the effectiveness of a physical therapy regimen versus corticosteroid injections for knee OA. Because he and his coinvestigators wanted a pragmatic study giving each treatment strategy its due, booster therapy was available to patients who requested it. Patients in the corticosteroid arm were able to receive up to two additional spaced intra-articular injections as needed, while those assigned to the individualized manual physical therapy intervention, which utilized exercises targeting the typical strength and movement deficits found in patients with knee OA, could have up to three additional sessions. At the outset, all participants received education about the benefits of regular low-impact physical activity, weight reduction, and strength and flexibility exercises.

The two treatment groups were comparable except that the physical therapy group had a longer disease duration – a mean of 123 months as compared with 89 in the corticosteroid group – and more radiographically severe disease. Indeed, 60% of patients randomized to physical therapy were Kellgren-Lawrence scale grade III-IV, versus 45% of those assigned to intra-articular corticosteroid injection.

The primary outcome in the study was change in Western Ontario & McMaster Universities Arthritis Index (WOMAC) score at 12 months. As early as 4 weeks into the study, the physical therapy group showed significantly greater improvement than in the comparison arm: from a mean baseline WOMAC score of 115 to 42.9 at 4 weeks, 42.5 at 6 months, and 38.4 at 1 year. The comparable figures in the intra-articular corticosteroid group were 113.3 at baseline, 53.3 at 4 weeks, 57.9 at 6 months, and 53.8 at 1 year.

“Physical therapy provided clinically important benefit that was superior to corticosteroid injection out to 1 year, while also providing the short-term benefit typically sought from corticosteroid injection,” Dr. Rhon observed.

The median improvement in WOMAC score at 1 year was 52% in the corticosteroid group and 71% in the physical therapy arm. About 59% of the physical therapy group experienced at least a 50% reduction in WOMAC score at 12 months, as did 38% of intra-articular injection recipients. The number needed to treat with physical therapy instead of intra-articular corticosteroids in order for one additional patient to achieve at least a 50% improvement in WOMAC score through 1 year of follow-up was four.

“We were a little bit surprised that there was such a large effect size in the study. The effect size in the injection group was bigger than reported in some other trials,” according to Dr. Rhon.

In terms of downstream utilization of health care, there were two knee arthroplasties and one arthroscopy in the study population, all in the intra-articular corticosteroid group. Seven patients in the intra-articular steroid group received more than three injections, including one patient with nine. And 13 patients in the physical therapy arm went outside the study in order to receive at least one corticosteroid injection.

One audience member pointed out that the physical therapy approach offers an important side benefit: In addition to improving pain and function, the exercise regimen has a favorable effect on comorbid metabolic diseases commonly associated with knee OA.

“An injection doesn’t achieve that,” he noted.

Dr. Rhon reported having no financial conflicts of interest regarding the randomized trial, sponsored by Madigan Army Medical Center. He receives research funding from the National Institutes of Health and the Congressionally Directed Medical Research Programs.

[email protected]

SOURCE: Rhon DI et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S32, Abstract 13

TORONTO – Eight physical therapy sessions spread over 4-6 weeks in patients with knee osteoarthritis provided significantly greater and longer-lasting improvements in both pain and function than an intra-articular corticosteroid injection in a randomized, multicenter trial with 12 months of prospective, blinded follow-up, Daniel I. Rhon, DPT, DSc, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Considering the very low utilization rate of physical therapy prior to arthroplasty, perhaps we should more often give it a try before declaring that conservative care has failed and moving on to surgical management,” concluded Dr. Rhon, director of the primary care musculoskeletal research center at Brooke Army Medical Center in San Antonio.

Various studies have shown that close to 50% of patients with knee OA receive one or more intra-articular corticosteroid injections within 5 years prior to undergoing total knee arthroplasty, compared with physical therapy in only about 10% of patients, even though most guidelines rate both as first-line therapies, he noted at the meeting sponsored by the Osteoarthritis Research Society International.

He presented a randomized trial of 156 patients who sought treatment for pain caused by knee OA at army medical center primary care clinics. To his knowledge, this was the first-ever randomized, head-to-head comparison of the effectiveness of a physical therapy regimen versus corticosteroid injections for knee OA. Because he and his coinvestigators wanted a pragmatic study giving each treatment strategy its due, booster therapy was available to patients who requested it. Patients in the corticosteroid arm were able to receive up to two additional spaced intra-articular injections as needed, while those assigned to the individualized manual physical therapy intervention, which utilized exercises targeting the typical strength and movement deficits found in patients with knee OA, could have up to three additional sessions. At the outset, all participants received education about the benefits of regular low-impact physical activity, weight reduction, and strength and flexibility exercises.

The two treatment groups were comparable except that the physical therapy group had a longer disease duration – a mean of 123 months as compared with 89 in the corticosteroid group – and more radiographically severe disease. Indeed, 60% of patients randomized to physical therapy were Kellgren-Lawrence scale grade III-IV, versus 45% of those assigned to intra-articular corticosteroid injection.

The primary outcome in the study was change in Western Ontario & McMaster Universities Arthritis Index (WOMAC) score at 12 months. As early as 4 weeks into the study, the physical therapy group showed significantly greater improvement than in the comparison arm: from a mean baseline WOMAC score of 115 to 42.9 at 4 weeks, 42.5 at 6 months, and 38.4 at 1 year. The comparable figures in the intra-articular corticosteroid group were 113.3 at baseline, 53.3 at 4 weeks, 57.9 at 6 months, and 53.8 at 1 year.

“Physical therapy provided clinically important benefit that was superior to corticosteroid injection out to 1 year, while also providing the short-term benefit typically sought from corticosteroid injection,” Dr. Rhon observed.

The median improvement in WOMAC score at 1 year was 52% in the corticosteroid group and 71% in the physical therapy arm. About 59% of the physical therapy group experienced at least a 50% reduction in WOMAC score at 12 months, as did 38% of intra-articular injection recipients. The number needed to treat with physical therapy instead of intra-articular corticosteroids in order for one additional patient to achieve at least a 50% improvement in WOMAC score through 1 year of follow-up was four.

“We were a little bit surprised that there was such a large effect size in the study. The effect size in the injection group was bigger than reported in some other trials,” according to Dr. Rhon.

In terms of downstream utilization of health care, there were two knee arthroplasties and one arthroscopy in the study population, all in the intra-articular corticosteroid group. Seven patients in the intra-articular steroid group received more than three injections, including one patient with nine. And 13 patients in the physical therapy arm went outside the study in order to receive at least one corticosteroid injection.

One audience member pointed out that the physical therapy approach offers an important side benefit: In addition to improving pain and function, the exercise regimen has a favorable effect on comorbid metabolic diseases commonly associated with knee OA.

“An injection doesn’t achieve that,” he noted.

Dr. Rhon reported having no financial conflicts of interest regarding the randomized trial, sponsored by Madigan Army Medical Center. He receives research funding from the National Institutes of Health and the Congressionally Directed Medical Research Programs.

[email protected]

SOURCE: Rhon DI et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S32, Abstract 13

TORONTO – Eight physical therapy sessions spread over 4-6 weeks in patients with knee osteoarthritis provided significantly greater and longer-lasting improvements in both pain and function than an intra-articular corticosteroid injection in a randomized, multicenter trial with 12 months of prospective, blinded follow-up, Daniel I. Rhon, DPT, DSc, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

“Considering the very low utilization rate of physical therapy prior to arthroplasty, perhaps we should more often give it a try before declaring that conservative care has failed and moving on to surgical management,” concluded Dr. Rhon, director of the primary care musculoskeletal research center at Brooke Army Medical Center in San Antonio.

Various studies have shown that close to 50% of patients with knee OA receive one or more intra-articular corticosteroid injections within 5 years prior to undergoing total knee arthroplasty, compared with physical therapy in only about 10% of patients, even though most guidelines rate both as first-line therapies, he noted at the meeting sponsored by the Osteoarthritis Research Society International.

He presented a randomized trial of 156 patients who sought treatment for pain caused by knee OA at army medical center primary care clinics. To his knowledge, this was the first-ever randomized, head-to-head comparison of the effectiveness of a physical therapy regimen versus corticosteroid injections for knee OA. Because he and his coinvestigators wanted a pragmatic study giving each treatment strategy its due, booster therapy was available to patients who requested it. Patients in the corticosteroid arm were able to receive up to two additional spaced intra-articular injections as needed, while those assigned to the individualized manual physical therapy intervention, which utilized exercises targeting the typical strength and movement deficits found in patients with knee OA, could have up to three additional sessions. At the outset, all participants received education about the benefits of regular low-impact physical activity, weight reduction, and strength and flexibility exercises.

The two treatment groups were comparable except that the physical therapy group had a longer disease duration – a mean of 123 months as compared with 89 in the corticosteroid group – and more radiographically severe disease. Indeed, 60% of patients randomized to physical therapy were Kellgren-Lawrence scale grade III-IV, versus 45% of those assigned to intra-articular corticosteroid injection.

The primary outcome in the study was change in Western Ontario & McMaster Universities Arthritis Index (WOMAC) score at 12 months. As early as 4 weeks into the study, the physical therapy group showed significantly greater improvement than in the comparison arm: from a mean baseline WOMAC score of 115 to 42.9 at 4 weeks, 42.5 at 6 months, and 38.4 at 1 year. The comparable figures in the intra-articular corticosteroid group were 113.3 at baseline, 53.3 at 4 weeks, 57.9 at 6 months, and 53.8 at 1 year.

“Physical therapy provided clinically important benefit that was superior to corticosteroid injection out to 1 year, while also providing the short-term benefit typically sought from corticosteroid injection,” Dr. Rhon observed.

The median improvement in WOMAC score at 1 year was 52% in the corticosteroid group and 71% in the physical therapy arm. About 59% of the physical therapy group experienced at least a 50% reduction in WOMAC score at 12 months, as did 38% of intra-articular injection recipients. The number needed to treat with physical therapy instead of intra-articular corticosteroids in order for one additional patient to achieve at least a 50% improvement in WOMAC score through 1 year of follow-up was four.

“We were a little bit surprised that there was such a large effect size in the study. The effect size in the injection group was bigger than reported in some other trials,” according to Dr. Rhon.

In terms of downstream utilization of health care, there were two knee arthroplasties and one arthroscopy in the study population, all in the intra-articular corticosteroid group. Seven patients in the intra-articular steroid group received more than three injections, including one patient with nine. And 13 patients in the physical therapy arm went outside the study in order to receive at least one corticosteroid injection.

One audience member pointed out that the physical therapy approach offers an important side benefit: In addition to improving pain and function, the exercise regimen has a favorable effect on comorbid metabolic diseases commonly associated with knee OA.

“An injection doesn’t achieve that,” he noted.

Dr. Rhon reported having no financial conflicts of interest regarding the randomized trial, sponsored by Madigan Army Medical Center. He receives research funding from the National Institutes of Health and the Congressionally Directed Medical Research Programs.

[email protected]

SOURCE: Rhon DI et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S32, Abstract 13