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Scandinavian studies shed light on OA inheritance
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.
“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.
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.
“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.
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.
“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.
SOURCE: Magnusson K et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S47, Abstract 33
REPORTING FROM OARSI 2019
Tanezumab acts fast for OA pain relief
TORONTO – , according to a secondary analysis of a phase 3 randomized trial.
“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.
SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.
TORONTO – , according to a secondary analysis of a phase 3 randomized trial.
“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.
SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.
TORONTO – , according to a secondary analysis of a phase 3 randomized trial.
“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.
SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.
REPORTING FROM OARSI 2019
Key clinical point: The nerve growth factor inhibitor tanezumab brings rapid improvement in pain.
Major finding: Tanezumab-treated patients experienced significant pain reduction within 3-5 days after their first dose.
Study details: This was a phase 3, prospective, multicenter, double-blind, placebo-controlled trial in 696 patients with refractory pain attributable to knee or hip OA.
Disclosures: The presenter reported serving as a consultant to Pfizer and Eli Lilly, which cosponsored the phase 3 trial.
Source: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.
Warfarin boosts OA risk in Rotterdam Study
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.
In a previous genetic study, she and her coinvestigators identified two genetic variants that result in loss of function of matrix Gla protein (MGP), a key inhibitor of cartilage calcification. They showed that the presence of these alleles was associated with a significantly increased risk of hand OA, which makes sense because increased calcification within a vulnerable joint promotes OA.
“The interesting thing here is that, in order for MGP to inhibit calcification, it needs to be gamma-carboxylated by vitamin K. If it’s not gamma-carboxylated it cannot inhibit calcification,” Ms. Boer said at the meeting sponsored by the Osteoarthritis Research Society International.
This observation led her to hypothesize that patients on warfarin or other vitamin K antagonists might have an increased risk of developing new-onset OA or, if they already had OA, of experiencing disease progression, since their medication inhibits MGP. To test this hypothesis, she and her coinvestigators turned to the landmark Rotterdam Study, a prospective, population-based cohort study of 15,000 participants, ongoing since 1990. Two large cohorts within the study had data available on the incidence and progression of radiographic knee and hip OA, one group over the course of 5 years of follow-up, the other with 10 years.
Serial x-rays of 8,845 knee joints were available, including 657 of warfarin users. Their rate of incident or progressive knee OA was 13%, compared with 5.9% in the nonusers in an analysis adjusted for age, sex, BMI, baseline OA status, and time between study visits.
In a similar vein, the rate of incident or progressive hip OA was 12% in the warfarin users, compared with 3.1% in nonusers.
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.
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.
In a previous genetic study, she and her coinvestigators identified two genetic variants that result in loss of function of matrix Gla protein (MGP), a key inhibitor of cartilage calcification. They showed that the presence of these alleles was associated with a significantly increased risk of hand OA, which makes sense because increased calcification within a vulnerable joint promotes OA.
“The interesting thing here is that, in order for MGP to inhibit calcification, it needs to be gamma-carboxylated by vitamin K. If it’s not gamma-carboxylated it cannot inhibit calcification,” Ms. Boer said at the meeting sponsored by the Osteoarthritis Research Society International.
This observation led her to hypothesize that patients on warfarin or other vitamin K antagonists might have an increased risk of developing new-onset OA or, if they already had OA, of experiencing disease progression, since their medication inhibits MGP. To test this hypothesis, she and her coinvestigators turned to the landmark Rotterdam Study, a prospective, population-based cohort study of 15,000 participants, ongoing since 1990. Two large cohorts within the study had data available on the incidence and progression of radiographic knee and hip OA, one group over the course of 5 years of follow-up, the other with 10 years.
Serial x-rays of 8,845 knee joints were available, including 657 of warfarin users. Their rate of incident or progressive knee OA was 13%, compared with 5.9% in the nonusers in an analysis adjusted for age, sex, BMI, baseline OA status, and time between study visits.
In a similar vein, the rate of incident or progressive hip OA was 12% in the warfarin users, compared with 3.1% in nonusers.
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.
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.
In a previous genetic study, she and her coinvestigators identified two genetic variants that result in loss of function of matrix Gla protein (MGP), a key inhibitor of cartilage calcification. They showed that the presence of these alleles was associated with a significantly increased risk of hand OA, which makes sense because increased calcification within a vulnerable joint promotes OA.
“The interesting thing here is that, in order for MGP to inhibit calcification, it needs to be gamma-carboxylated by vitamin K. If it’s not gamma-carboxylated it cannot inhibit calcification,” Ms. Boer said at the meeting sponsored by the Osteoarthritis Research Society International.
This observation led her to hypothesize that patients on warfarin or other vitamin K antagonists might have an increased risk of developing new-onset OA or, if they already had OA, of experiencing disease progression, since their medication inhibits MGP. To test this hypothesis, she and her coinvestigators turned to the landmark Rotterdam Study, a prospective, population-based cohort study of 15,000 participants, ongoing since 1990. Two large cohorts within the study had data available on the incidence and progression of radiographic knee and hip OA, one group over the course of 5 years of follow-up, the other with 10 years.
Serial x-rays of 8,845 knee joints were available, including 657 of warfarin users. Their rate of incident or progressive knee OA was 13%, compared with 5.9% in the nonusers in an analysis adjusted for age, sex, BMI, baseline OA status, and time between study visits.
In a similar vein, the rate of incident or progressive hip OA was 12% in the warfarin users, compared with 3.1% in nonusers.
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.
REPORTING FROM OARSI 2019
Upcoming OA management guidelines reveal dearth of effective therapies
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.
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.
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.
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.
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.
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.
REPORTING FROM OARSI 2019
Patients rate burden of OA equal to RA
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.
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.
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.
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.
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.
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.
REPORTING FROM OARSI 2019
Bundled payment for OA surgery linked to more emergency department visits
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.
SOURCE: Canizares M. OARSI, Abstract 16.
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.
SOURCE: Canizares M. OARSI, Abstract 16.
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.
SOURCE: Canizares M. OARSI, Abstract 16.
REPORTING FROM OARSI 2019
PT beats steroid injections for knee OA
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.
“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.
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.
“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.
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.
“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.
SOURCE: Rhon DI et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S32, Abstract 13
REPORTING FROM OARSI 2019
High-intensity statins may cut risk of joint replacement
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
REPORTING FROM OARSI 2019
Key clinical point: High-intensity statin therapy may reduce need for joint replacement in arthritis.
Major finding: The risk of knee or hip replacement surgery for rheumatoid arthritis was slashed by 90%, and by 21% for osteoarthritis.
Study details: This study included nearly 180,000 statin users propensity score-matched to an equal number of nonusers and prospectively followed for a mean of 6.5 years.
Disclosures: The study was supported by the National Clinical Research Center of Geriatric Disorders at Central South University in Hunan, China, and by several British universities. The presenter reported having no financial conflicts of interest.
Source: Sarmanova A et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.