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For MD-IQ on Family Practice News, but a regular topic for Rheumatology News
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.
Arthritis joint pain, inactivity vary greatly across U.S.
Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.
Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).
The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.
The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.
“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”
SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.
Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.
Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).
The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.
The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.
“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”
SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.
Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.
Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).
The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.
The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.
“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”
SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.
FROM MMWR
Four biomarkers could distinguish psoriatic arthritis from osteoarthritis
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
FROM ANNALS OF THE RHEUMATIC DISEASES
Industry-funded rheumatology RCTs are higher quality
MAUI, HAWAII – Industry-funded randomized, controlled clinical trials published in the three top-rated rheumatology journals during the past 20 years are of significantly higher overall quality than the nonindustry-funded ones, Michael Putman, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
Dr. Putman, a second-year rheumatology fellow at Northwestern University, Chicago, analyzed all randomized, controlled trials (RCTs) of pharmacotherapy featuring a comparator – either placebo or an active agent – published in 1998, 2008, and 2018 in Annals of the Rheumatic Diseases, Rheumatology, and Arthritis & Rheumatology.
His main takeaway: “Rheumatologic interventions seem to work pretty well. The mean absolute risk reduction in the trials is 17.5%, so the average number of patients who need to be treated with a rheumatologic intervention is about five. This is why it’s such a great specialty to be a part of: A lot of our patients get better.”
He created an RCT quality rating scale that captured the strength of study design, methodology, and findings based upon whether a randomized trial used a double-blind design; identified a prespecified primary outcome; and featured patient-reported outcomes, power calculations, sensitivity analysis, adjustment for multiple hypotheses, and intention-to-treat analysis. He then applied the rating scale to the 85 published RCTs in the three study years.
Of note, 84% of the trials published in 2018 were industry funded, up from 74% in 2008 and 1998.
“Industry funds the vast majority of studies. Industry studies are significantly more likely to be appropriately double blinded, report patient-reported outcome measures, use intention to treat, and they have a higher overall quality,” according to Dr. Putman.
Indeed, the industry-funded studies averaged a 66% score on his quality grading scale, compared with 45% for nonindustry-funded studies.
Utilization of most of the quality metrics remained stable over time. The exceptions: Incorporation of intent-to-treat analysis increased from 58% in 1998 to 87% in 2018, and sensitivity analysis was employed in just 5% of the trials published in 1998, compared with 37% in 2008 and 26% in 2018.
The most important change over the past 2 decades, in his view, has been the shrinking proportion of RCTs featuring an active-drug, head-to-head comparator arm. In 1998, 42% of studies featured that design; for example, comparing methotrexate to sulfasalazine. By 2018, that figure had dropped to just 13%.
“Most of our trials today compare an active compound, such an interleukin-17 inhibitor, to a placebo. I think that’s a big change in how we do things,” Dr. Putman observed. “With 84% of our studies being funded by industry, the incentives in medicine right now don’t support active comparator research. It’s harder to show a difference between two things that work than it is to show a difference between something and nothing.”
However, he’d welcome a revival of head-to-head active comparator trials.
“I’d really love to have that happen,” he said. “We have basic questions we haven’t answered yet about a lot of our basic drugs: Like in myositis, should you start with Imuran [azathioprine], CellCept [mycophenolate mofetil], or methotrexate?”
Another striking change over time has been the dwindling proportion of published trials with a statistically significant finding for the primary outcome: 79% in 1998, 46% in 2008, and 36% last year. Dr. Putman suspects the explanation lies in the steady improvement in the effectiveness of standard background therapy for many conditions, which makes it tougher to show a striking difference between the add-on study drug and add-on placebo.
“We’re a victim of our own success,” he commented.
In any event, many key secondary outcomes in the RCTs were positive, even when the primary endpoint wasn’t, according to Dr. Putman, and there was a notable dearth of completely negative clinical RCTs published in the three top journals.
“The more cynical interpretation is there’s an incredible amount of publication bias, where we’re only publishing studies that show an effect and the journals or investigators are censoring the ones that don’t. The more charitable explanation, which is probably also true, is that by the time you get to putting on an RCT you kind of think, ‘This thing works.’ You’re not testing random stuff, so your pretest probability of a drug being effective when it enters into an RCT is probably shifted toward effectiveness,” Dr. Putman speculated.
He reported having no financial conflicts regarding his study.
MAUI, HAWAII – Industry-funded randomized, controlled clinical trials published in the three top-rated rheumatology journals during the past 20 years are of significantly higher overall quality than the nonindustry-funded ones, Michael Putman, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
Dr. Putman, a second-year rheumatology fellow at Northwestern University, Chicago, analyzed all randomized, controlled trials (RCTs) of pharmacotherapy featuring a comparator – either placebo or an active agent – published in 1998, 2008, and 2018 in Annals of the Rheumatic Diseases, Rheumatology, and Arthritis & Rheumatology.
His main takeaway: “Rheumatologic interventions seem to work pretty well. The mean absolute risk reduction in the trials is 17.5%, so the average number of patients who need to be treated with a rheumatologic intervention is about five. This is why it’s such a great specialty to be a part of: A lot of our patients get better.”
He created an RCT quality rating scale that captured the strength of study design, methodology, and findings based upon whether a randomized trial used a double-blind design; identified a prespecified primary outcome; and featured patient-reported outcomes, power calculations, sensitivity analysis, adjustment for multiple hypotheses, and intention-to-treat analysis. He then applied the rating scale to the 85 published RCTs in the three study years.
Of note, 84% of the trials published in 2018 were industry funded, up from 74% in 2008 and 1998.
“Industry funds the vast majority of studies. Industry studies are significantly more likely to be appropriately double blinded, report patient-reported outcome measures, use intention to treat, and they have a higher overall quality,” according to Dr. Putman.
Indeed, the industry-funded studies averaged a 66% score on his quality grading scale, compared with 45% for nonindustry-funded studies.
Utilization of most of the quality metrics remained stable over time. The exceptions: Incorporation of intent-to-treat analysis increased from 58% in 1998 to 87% in 2018, and sensitivity analysis was employed in just 5% of the trials published in 1998, compared with 37% in 2008 and 26% in 2018.
The most important change over the past 2 decades, in his view, has been the shrinking proportion of RCTs featuring an active-drug, head-to-head comparator arm. In 1998, 42% of studies featured that design; for example, comparing methotrexate to sulfasalazine. By 2018, that figure had dropped to just 13%.
“Most of our trials today compare an active compound, such an interleukin-17 inhibitor, to a placebo. I think that’s a big change in how we do things,” Dr. Putman observed. “With 84% of our studies being funded by industry, the incentives in medicine right now don’t support active comparator research. It’s harder to show a difference between two things that work than it is to show a difference between something and nothing.”
However, he’d welcome a revival of head-to-head active comparator trials.
“I’d really love to have that happen,” he said. “We have basic questions we haven’t answered yet about a lot of our basic drugs: Like in myositis, should you start with Imuran [azathioprine], CellCept [mycophenolate mofetil], or methotrexate?”
Another striking change over time has been the dwindling proportion of published trials with a statistically significant finding for the primary outcome: 79% in 1998, 46% in 2008, and 36% last year. Dr. Putman suspects the explanation lies in the steady improvement in the effectiveness of standard background therapy for many conditions, which makes it tougher to show a striking difference between the add-on study drug and add-on placebo.
“We’re a victim of our own success,” he commented.
In any event, many key secondary outcomes in the RCTs were positive, even when the primary endpoint wasn’t, according to Dr. Putman, and there was a notable dearth of completely negative clinical RCTs published in the three top journals.
“The more cynical interpretation is there’s an incredible amount of publication bias, where we’re only publishing studies that show an effect and the journals or investigators are censoring the ones that don’t. The more charitable explanation, which is probably also true, is that by the time you get to putting on an RCT you kind of think, ‘This thing works.’ You’re not testing random stuff, so your pretest probability of a drug being effective when it enters into an RCT is probably shifted toward effectiveness,” Dr. Putman speculated.
He reported having no financial conflicts regarding his study.
MAUI, HAWAII – Industry-funded randomized, controlled clinical trials published in the three top-rated rheumatology journals during the past 20 years are of significantly higher overall quality than the nonindustry-funded ones, Michael Putman, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
Dr. Putman, a second-year rheumatology fellow at Northwestern University, Chicago, analyzed all randomized, controlled trials (RCTs) of pharmacotherapy featuring a comparator – either placebo or an active agent – published in 1998, 2008, and 2018 in Annals of the Rheumatic Diseases, Rheumatology, and Arthritis & Rheumatology.
His main takeaway: “Rheumatologic interventions seem to work pretty well. The mean absolute risk reduction in the trials is 17.5%, so the average number of patients who need to be treated with a rheumatologic intervention is about five. This is why it’s such a great specialty to be a part of: A lot of our patients get better.”
He created an RCT quality rating scale that captured the strength of study design, methodology, and findings based upon whether a randomized trial used a double-blind design; identified a prespecified primary outcome; and featured patient-reported outcomes, power calculations, sensitivity analysis, adjustment for multiple hypotheses, and intention-to-treat analysis. He then applied the rating scale to the 85 published RCTs in the three study years.
Of note, 84% of the trials published in 2018 were industry funded, up from 74% in 2008 and 1998.
“Industry funds the vast majority of studies. Industry studies are significantly more likely to be appropriately double blinded, report patient-reported outcome measures, use intention to treat, and they have a higher overall quality,” according to Dr. Putman.
Indeed, the industry-funded studies averaged a 66% score on his quality grading scale, compared with 45% for nonindustry-funded studies.
Utilization of most of the quality metrics remained stable over time. The exceptions: Incorporation of intent-to-treat analysis increased from 58% in 1998 to 87% in 2018, and sensitivity analysis was employed in just 5% of the trials published in 1998, compared with 37% in 2008 and 26% in 2018.
The most important change over the past 2 decades, in his view, has been the shrinking proportion of RCTs featuring an active-drug, head-to-head comparator arm. In 1998, 42% of studies featured that design; for example, comparing methotrexate to sulfasalazine. By 2018, that figure had dropped to just 13%.
“Most of our trials today compare an active compound, such an interleukin-17 inhibitor, to a placebo. I think that’s a big change in how we do things,” Dr. Putman observed. “With 84% of our studies being funded by industry, the incentives in medicine right now don’t support active comparator research. It’s harder to show a difference between two things that work than it is to show a difference between something and nothing.”
However, he’d welcome a revival of head-to-head active comparator trials.
“I’d really love to have that happen,” he said. “We have basic questions we haven’t answered yet about a lot of our basic drugs: Like in myositis, should you start with Imuran [azathioprine], CellCept [mycophenolate mofetil], or methotrexate?”
Another striking change over time has been the dwindling proportion of published trials with a statistically significant finding for the primary outcome: 79% in 1998, 46% in 2008, and 36% last year. Dr. Putman suspects the explanation lies in the steady improvement in the effectiveness of standard background therapy for many conditions, which makes it tougher to show a striking difference between the add-on study drug and add-on placebo.
“We’re a victim of our own success,” he commented.
In any event, many key secondary outcomes in the RCTs were positive, even when the primary endpoint wasn’t, according to Dr. Putman, and there was a notable dearth of completely negative clinical RCTs published in the three top journals.
“The more cynical interpretation is there’s an incredible amount of publication bias, where we’re only publishing studies that show an effect and the journals or investigators are censoring the ones that don’t. The more charitable explanation, which is probably also true, is that by the time you get to putting on an RCT you kind of think, ‘This thing works.’ You’re not testing random stuff, so your pretest probability of a drug being effective when it enters into an RCT is probably shifted toward effectiveness,” Dr. Putman speculated.
He reported having no financial conflicts regarding his study.
REPORTING FROM RWCS 2019
Disease burden in OA worse than RA 6 months post presentation
Patients with osteoarthritis (OA) have RAPID3 scores at their initial visit (16.0) similar to patients with rheumatoid arthritis (RA) and either prior use of disease-modifying antirheumatic drugs (DMARDs) or no exposure to DMARDs (15.6 and 15.5, respectively). After 6 months of treatment, the RAPID3 (Routine Assessment of Patient Index Data 3) score fell by just 1.7 points for patients with OA, compared with 5.7 points in RA patients naive to DMARDs and 4.3 points in those with prior DMARD exposure. These findings were published March 20 in Arthritis & Rheumatology (doi: 10.1002/art.40869).
We reported this story at the 2018 World Congress on Osteoarthritis before it was published in the journal. Read the story at the link above.
Patients with osteoarthritis (OA) have RAPID3 scores at their initial visit (16.0) similar to patients with rheumatoid arthritis (RA) and either prior use of disease-modifying antirheumatic drugs (DMARDs) or no exposure to DMARDs (15.6 and 15.5, respectively). After 6 months of treatment, the RAPID3 (Routine Assessment of Patient Index Data 3) score fell by just 1.7 points for patients with OA, compared with 5.7 points in RA patients naive to DMARDs and 4.3 points in those with prior DMARD exposure. These findings were published March 20 in Arthritis & Rheumatology (doi: 10.1002/art.40869).
We reported this story at the 2018 World Congress on Osteoarthritis before it was published in the journal. Read the story at the link above.
Patients with osteoarthritis (OA) have RAPID3 scores at their initial visit (16.0) similar to patients with rheumatoid arthritis (RA) and either prior use of disease-modifying antirheumatic drugs (DMARDs) or no exposure to DMARDs (15.6 and 15.5, respectively). After 6 months of treatment, the RAPID3 (Routine Assessment of Patient Index Data 3) score fell by just 1.7 points for patients with OA, compared with 5.7 points in RA patients naive to DMARDs and 4.3 points in those with prior DMARD exposure. These findings were published March 20 in Arthritis & Rheumatology (doi: 10.1002/art.40869).
We reported this story at the 2018 World Congress on Osteoarthritis before it was published in the journal. Read the story at the link above.
FROM ARTHRITIS & RHEUMATOLOGY
Possible mortality risk seen with tramadol in osteoarthritis
Tramadol appears to be associated with higher mortality risk among older patients with osteoarthritis when compared against common NSAIDs, according to findings from a study published online March 12 in JAMA.
The findings from the retrospective cohort study are worth noting despite their susceptibility to confounding by indication because “tramadol is a weak opioid agonist and has been considered a potential alternative to NSAIDs and traditional opioids because of its assumed relatively lower risk of serious cardiovascular and gastrointestinal adverse effects than NSAIDs, as well as a lower risk of addiction and respiratory depression compared with other opioids,” wrote Chao Zeng, MD, PhD, of Xiangya Hospital of Central South University, Changsha, China, and his coauthors.
The investigators analyzed data from a combined total of 88,902 individuals aged 50 years and older with knee, hip, or hand osteoarthritis who were seen during 2000-2015 and had visits recorded in the United Kingdom’s The Health Improvement Network (THIN) electronic medical records database. Participants were matched on sociodemographic and lifestyle factors, as well as osteoarthritis duration, comorbidities, other prescriptions, and health care utilization prior to the index date of the study.
Over 1 year of follow-up, researchers saw a 71% higher risk of all-cause mortality in patients taking tramadol than that in seen in those taking naproxen, 88% higher than in those taking diclofenac, 70% higher than in those taking celecoxib, and about twice as high as in patients taking etoricoxib.
However, there was no significant difference in risk of all-cause mortality between tramadol and codeine, the researchers found.
The authors suggested that tramadol may have adverse effects on the neurologic system by inhibiting central serotonin and norepinephrine uptake, which could potentially lead to serotonin syndrome. They also speculated that it could increase the risk of postoperative delirium, cause fatal poisoning or respiratory depression if taken in conjunction with alcohol or other drugs, or increase the risk of hypoglycemia, hyponatremia, fractures, or falls.
The numbers of deaths from cardiovascular, gastrointestinal, infection, cancer, and respiratory diseases were all higher in the tramadol group, compared with patients taking NSAIDs, but the differences were not statistically significant because of the relatively small number of deaths, the authors said.
Overall, 44,451 patients were taking tramadol, 12,397 were taking naproxen, 6,512 were taking diclofenac, 5,674 were taking celecoxib, 2,946 were taking etoricoxib, and 16,922 were taking codeine.
Patients in the tramadol cohort were generally older, with higher body mass index, a longer duration of osteoarthritis, and had a higher prevalence of comorbidities, higher health care utilization, and more prescriptions of other medications.
The authors noted that, while the patients from each medication cohort were matched on propensity score, the results were still susceptible to confounding by indication and should be interpreted with caution.
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Natural Science Foundation of China. One author declared funding from the National Institute on Drug Abuse during the conduct of the study and grants from Optum Labs outside the study. No other conflicts of interest were declared.
SOURCE: Zeng C et al. JAMA. 2019;321:969-82.
Tramadol appears to be associated with higher mortality risk among older patients with osteoarthritis when compared against common NSAIDs, according to findings from a study published online March 12 in JAMA.
The findings from the retrospective cohort study are worth noting despite their susceptibility to confounding by indication because “tramadol is a weak opioid agonist and has been considered a potential alternative to NSAIDs and traditional opioids because of its assumed relatively lower risk of serious cardiovascular and gastrointestinal adverse effects than NSAIDs, as well as a lower risk of addiction and respiratory depression compared with other opioids,” wrote Chao Zeng, MD, PhD, of Xiangya Hospital of Central South University, Changsha, China, and his coauthors.
The investigators analyzed data from a combined total of 88,902 individuals aged 50 years and older with knee, hip, or hand osteoarthritis who were seen during 2000-2015 and had visits recorded in the United Kingdom’s The Health Improvement Network (THIN) electronic medical records database. Participants were matched on sociodemographic and lifestyle factors, as well as osteoarthritis duration, comorbidities, other prescriptions, and health care utilization prior to the index date of the study.
Over 1 year of follow-up, researchers saw a 71% higher risk of all-cause mortality in patients taking tramadol than that in seen in those taking naproxen, 88% higher than in those taking diclofenac, 70% higher than in those taking celecoxib, and about twice as high as in patients taking etoricoxib.
However, there was no significant difference in risk of all-cause mortality between tramadol and codeine, the researchers found.
The authors suggested that tramadol may have adverse effects on the neurologic system by inhibiting central serotonin and norepinephrine uptake, which could potentially lead to serotonin syndrome. They also speculated that it could increase the risk of postoperative delirium, cause fatal poisoning or respiratory depression if taken in conjunction with alcohol or other drugs, or increase the risk of hypoglycemia, hyponatremia, fractures, or falls.
The numbers of deaths from cardiovascular, gastrointestinal, infection, cancer, and respiratory diseases were all higher in the tramadol group, compared with patients taking NSAIDs, but the differences were not statistically significant because of the relatively small number of deaths, the authors said.
Overall, 44,451 patients were taking tramadol, 12,397 were taking naproxen, 6,512 were taking diclofenac, 5,674 were taking celecoxib, 2,946 were taking etoricoxib, and 16,922 were taking codeine.
Patients in the tramadol cohort were generally older, with higher body mass index, a longer duration of osteoarthritis, and had a higher prevalence of comorbidities, higher health care utilization, and more prescriptions of other medications.
The authors noted that, while the patients from each medication cohort were matched on propensity score, the results were still susceptible to confounding by indication and should be interpreted with caution.
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Natural Science Foundation of China. One author declared funding from the National Institute on Drug Abuse during the conduct of the study and grants from Optum Labs outside the study. No other conflicts of interest were declared.
SOURCE: Zeng C et al. JAMA. 2019;321:969-82.
Tramadol appears to be associated with higher mortality risk among older patients with osteoarthritis when compared against common NSAIDs, according to findings from a study published online March 12 in JAMA.
The findings from the retrospective cohort study are worth noting despite their susceptibility to confounding by indication because “tramadol is a weak opioid agonist and has been considered a potential alternative to NSAIDs and traditional opioids because of its assumed relatively lower risk of serious cardiovascular and gastrointestinal adverse effects than NSAIDs, as well as a lower risk of addiction and respiratory depression compared with other opioids,” wrote Chao Zeng, MD, PhD, of Xiangya Hospital of Central South University, Changsha, China, and his coauthors.
The investigators analyzed data from a combined total of 88,902 individuals aged 50 years and older with knee, hip, or hand osteoarthritis who were seen during 2000-2015 and had visits recorded in the United Kingdom’s The Health Improvement Network (THIN) electronic medical records database. Participants were matched on sociodemographic and lifestyle factors, as well as osteoarthritis duration, comorbidities, other prescriptions, and health care utilization prior to the index date of the study.
Over 1 year of follow-up, researchers saw a 71% higher risk of all-cause mortality in patients taking tramadol than that in seen in those taking naproxen, 88% higher than in those taking diclofenac, 70% higher than in those taking celecoxib, and about twice as high as in patients taking etoricoxib.
However, there was no significant difference in risk of all-cause mortality between tramadol and codeine, the researchers found.
The authors suggested that tramadol may have adverse effects on the neurologic system by inhibiting central serotonin and norepinephrine uptake, which could potentially lead to serotonin syndrome. They also speculated that it could increase the risk of postoperative delirium, cause fatal poisoning or respiratory depression if taken in conjunction with alcohol or other drugs, or increase the risk of hypoglycemia, hyponatremia, fractures, or falls.
The numbers of deaths from cardiovascular, gastrointestinal, infection, cancer, and respiratory diseases were all higher in the tramadol group, compared with patients taking NSAIDs, but the differences were not statistically significant because of the relatively small number of deaths, the authors said.
Overall, 44,451 patients were taking tramadol, 12,397 were taking naproxen, 6,512 were taking diclofenac, 5,674 were taking celecoxib, 2,946 were taking etoricoxib, and 16,922 were taking codeine.
Patients in the tramadol cohort were generally older, with higher body mass index, a longer duration of osteoarthritis, and had a higher prevalence of comorbidities, higher health care utilization, and more prescriptions of other medications.
The authors noted that, while the patients from each medication cohort were matched on propensity score, the results were still susceptible to confounding by indication and should be interpreted with caution.
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Natural Science Foundation of China. One author declared funding from the National Institute on Drug Abuse during the conduct of the study and grants from Optum Labs outside the study. No other conflicts of interest were declared.
SOURCE: Zeng C et al. JAMA. 2019;321:969-82.
FROM JAMA
Long-term opioid use substantial in elderly adults prior to total joint replacement
In elderly patients with osteoarthritis, long-term opioid use is highly prevalent and varies substantially by state, suggest the results of a large, observational cohort study.
Long term opioid use prior to total joint replacement (TJR) varied somewhat by access to primary care providers, but not by access to rheumatologists, according to authors of the study, led by Rishi J Desai, MS, PhD, of the department of medicine at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
“These findings suggest that geographically targeted dissemination strategies for safe opioid prescribing guidelines may be required to address the high use observed in certain states,” said Dr. Desai and his colleagues in a report on the study published in Arthritis & Rheumatology.
This study by Dr. Desai and his colleagues looked at long-term use of opioids, which was defined as at least 90 days of use in the year prior to TJR. They analyzed a total of 358,121 Medicare enrollees with advanced osteoarthritis, with a mean age of 74 years.
Geographic areas in the South tended to have higher proportions of long-term opioid users, while the Northeast and Midwest had lower proportions, according to investigators.
Long-term use of opioids ranged from a low of 8.9% in Minnesota to 26.4% in Alabama, they reported. Beyond Alabama, the top 10 states included West Virginia, Georgia, Kentucky, Louisiana, Oklahoma, North Carolina, Virginia, Indiana, and Mississippi, with proportions of long-term opioid users ranging from 17% to 25%, the report shows.
Only modest associations were seen between provider density and opioid use, investigators said. There was a 1.4% mean difference (95% confidence interval, 0.8%-2.0%) in long-term opioid users between primary care service areas (PCSAs) with the highest concentrations of primary care providers versus those with the lowest, and there was just a 0.6% mean difference (95% CI, –0.1% to 1.3%) between PCSAs with the highest concentrations of rheumatologists and those with the lowest.
Among long-term opioid users, almost 20% were using an average daily dose of 50 or more morphine milligram equivalents, a range that potentially imparts a high risk of opioid-related harms, according to investigators.
Funding for the study came from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Desai reported disclosures related to Merck and Vertex. Co-authors provided disclosures related to a number of pharmaceutical companies.
SOURCE: Desai RJ et al. Arthritis Rheumatol. 2019. doi: 10.1002/art.40834.
In elderly patients with osteoarthritis, long-term opioid use is highly prevalent and varies substantially by state, suggest the results of a large, observational cohort study.
Long term opioid use prior to total joint replacement (TJR) varied somewhat by access to primary care providers, but not by access to rheumatologists, according to authors of the study, led by Rishi J Desai, MS, PhD, of the department of medicine at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
“These findings suggest that geographically targeted dissemination strategies for safe opioid prescribing guidelines may be required to address the high use observed in certain states,” said Dr. Desai and his colleagues in a report on the study published in Arthritis & Rheumatology.
This study by Dr. Desai and his colleagues looked at long-term use of opioids, which was defined as at least 90 days of use in the year prior to TJR. They analyzed a total of 358,121 Medicare enrollees with advanced osteoarthritis, with a mean age of 74 years.
Geographic areas in the South tended to have higher proportions of long-term opioid users, while the Northeast and Midwest had lower proportions, according to investigators.
Long-term use of opioids ranged from a low of 8.9% in Minnesota to 26.4% in Alabama, they reported. Beyond Alabama, the top 10 states included West Virginia, Georgia, Kentucky, Louisiana, Oklahoma, North Carolina, Virginia, Indiana, and Mississippi, with proportions of long-term opioid users ranging from 17% to 25%, the report shows.
Only modest associations were seen between provider density and opioid use, investigators said. There was a 1.4% mean difference (95% confidence interval, 0.8%-2.0%) in long-term opioid users between primary care service areas (PCSAs) with the highest concentrations of primary care providers versus those with the lowest, and there was just a 0.6% mean difference (95% CI, –0.1% to 1.3%) between PCSAs with the highest concentrations of rheumatologists and those with the lowest.
Among long-term opioid users, almost 20% were using an average daily dose of 50 or more morphine milligram equivalents, a range that potentially imparts a high risk of opioid-related harms, according to investigators.
Funding for the study came from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Desai reported disclosures related to Merck and Vertex. Co-authors provided disclosures related to a number of pharmaceutical companies.
SOURCE: Desai RJ et al. Arthritis Rheumatol. 2019. doi: 10.1002/art.40834.
In elderly patients with osteoarthritis, long-term opioid use is highly prevalent and varies substantially by state, suggest the results of a large, observational cohort study.
Long term opioid use prior to total joint replacement (TJR) varied somewhat by access to primary care providers, but not by access to rheumatologists, according to authors of the study, led by Rishi J Desai, MS, PhD, of the department of medicine at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
“These findings suggest that geographically targeted dissemination strategies for safe opioid prescribing guidelines may be required to address the high use observed in certain states,” said Dr. Desai and his colleagues in a report on the study published in Arthritis & Rheumatology.
This study by Dr. Desai and his colleagues looked at long-term use of opioids, which was defined as at least 90 days of use in the year prior to TJR. They analyzed a total of 358,121 Medicare enrollees with advanced osteoarthritis, with a mean age of 74 years.
Geographic areas in the South tended to have higher proportions of long-term opioid users, while the Northeast and Midwest had lower proportions, according to investigators.
Long-term use of opioids ranged from a low of 8.9% in Minnesota to 26.4% in Alabama, they reported. Beyond Alabama, the top 10 states included West Virginia, Georgia, Kentucky, Louisiana, Oklahoma, North Carolina, Virginia, Indiana, and Mississippi, with proportions of long-term opioid users ranging from 17% to 25%, the report shows.
Only modest associations were seen between provider density and opioid use, investigators said. There was a 1.4% mean difference (95% confidence interval, 0.8%-2.0%) in long-term opioid users between primary care service areas (PCSAs) with the highest concentrations of primary care providers versus those with the lowest, and there was just a 0.6% mean difference (95% CI, –0.1% to 1.3%) between PCSAs with the highest concentrations of rheumatologists and those with the lowest.
Among long-term opioid users, almost 20% were using an average daily dose of 50 or more morphine milligram equivalents, a range that potentially imparts a high risk of opioid-related harms, according to investigators.
Funding for the study came from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Desai reported disclosures related to Merck and Vertex. Co-authors provided disclosures related to a number of pharmaceutical companies.
SOURCE: Desai RJ et al. Arthritis Rheumatol. 2019. doi: 10.1002/art.40834.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Long-term opioid use is highly prevalent among older adults with osteoarthritis who underwent total joint replacement.
Major finding: Long-term use of opioids ranged from a low of 8.9% in Minnesota to 26.4% in Alabama.
Study details: An observational cohort study including 358,121 Medicare enrollees with advanced osteoarthritis.
Disclosures: Funding for the study came from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Desai reported disclosures related to Merck and Vertex. Coauthors provided disclosures related to a number of pharmaceutical companies.
Source: Desai RJ et al. Arthritis Rheumatol. 2019. doi: 10.1002/art.40834.
Heberden’s nodes linked to knee OA progression
according to a review of 575 participants in a substudy of the Osteoarthritis Initiative cohort.
After assessing Heberden’s nodes (HNs) – bony enlargements of the last finger joint – and knee MRI findings at baseline and 24 months, the investigators found that HNs were associated with periarticular bone area expansion in the knee. The investigators reported their findings in Arthritis & Rheumatology.
Comparing the 395 subjects with HNs with the 180 without, there was more periarticular bone area expansion among HN patients at 2 years in the knee joint (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.83), especially in the medial femur (aOR, 1.49; 95% CI, 1.05-2.13), lateral femur (aOR, 2.51; 95% CI, 1.58-3.97), femoral notch (aOR, 1.37; 95% CI, 1.02-1.84), and lateral trochlea (aOR, 1.44; 95% CI, 1.08-1.9). The comparisons were adjusted for age, sex, body mass index, and bone remodeling agent use.
“The presence of Heberden’s nodes in a physical examination is associated with a distinct pattern of worsening of osteoarthritis-related structural damage in the knee joint,” lead investigator Arya Haj-Mirzaian, MD, a radiologist and postdoctoral fellow at Johns Hopkins University, Baltimore, said in a press release.
However, HNs were also associated with less worsening of knee osteophytes, especially at the femoral end of the knee joint (aOR, 0.54; 95% CI, 0.31-0.95); the finding seemed to contradict the overall picture of worsening knee osteoarthritis with HNs.
“Although osteophytes are thought to be a late secondary sequel or compensatory repair mechanism in OA and indicator of advanced knee OA, less worsening in osteophytes’ score ... may propose that less ossification is involved in the pathophysiology of knee OA in the presence of HNs,” the investigators wrote. It’s a subject for future research.
Patients with HNs were older, more often female, and had a lower frequency for other knee OA risk factors, such as excessive body mass index and knee injury. Patients with gout were excluded.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Haj-Mirzaian A et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40811.
according to a review of 575 participants in a substudy of the Osteoarthritis Initiative cohort.
After assessing Heberden’s nodes (HNs) – bony enlargements of the last finger joint – and knee MRI findings at baseline and 24 months, the investigators found that HNs were associated with periarticular bone area expansion in the knee. The investigators reported their findings in Arthritis & Rheumatology.
Comparing the 395 subjects with HNs with the 180 without, there was more periarticular bone area expansion among HN patients at 2 years in the knee joint (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.83), especially in the medial femur (aOR, 1.49; 95% CI, 1.05-2.13), lateral femur (aOR, 2.51; 95% CI, 1.58-3.97), femoral notch (aOR, 1.37; 95% CI, 1.02-1.84), and lateral trochlea (aOR, 1.44; 95% CI, 1.08-1.9). The comparisons were adjusted for age, sex, body mass index, and bone remodeling agent use.
“The presence of Heberden’s nodes in a physical examination is associated with a distinct pattern of worsening of osteoarthritis-related structural damage in the knee joint,” lead investigator Arya Haj-Mirzaian, MD, a radiologist and postdoctoral fellow at Johns Hopkins University, Baltimore, said in a press release.
However, HNs were also associated with less worsening of knee osteophytes, especially at the femoral end of the knee joint (aOR, 0.54; 95% CI, 0.31-0.95); the finding seemed to contradict the overall picture of worsening knee osteoarthritis with HNs.
“Although osteophytes are thought to be a late secondary sequel or compensatory repair mechanism in OA and indicator of advanced knee OA, less worsening in osteophytes’ score ... may propose that less ossification is involved in the pathophysiology of knee OA in the presence of HNs,” the investigators wrote. It’s a subject for future research.
Patients with HNs were older, more often female, and had a lower frequency for other knee OA risk factors, such as excessive body mass index and knee injury. Patients with gout were excluded.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Haj-Mirzaian A et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40811.
according to a review of 575 participants in a substudy of the Osteoarthritis Initiative cohort.
After assessing Heberden’s nodes (HNs) – bony enlargements of the last finger joint – and knee MRI findings at baseline and 24 months, the investigators found that HNs were associated with periarticular bone area expansion in the knee. The investigators reported their findings in Arthritis & Rheumatology.
Comparing the 395 subjects with HNs with the 180 without, there was more periarticular bone area expansion among HN patients at 2 years in the knee joint (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.83), especially in the medial femur (aOR, 1.49; 95% CI, 1.05-2.13), lateral femur (aOR, 2.51; 95% CI, 1.58-3.97), femoral notch (aOR, 1.37; 95% CI, 1.02-1.84), and lateral trochlea (aOR, 1.44; 95% CI, 1.08-1.9). The comparisons were adjusted for age, sex, body mass index, and bone remodeling agent use.
“The presence of Heberden’s nodes in a physical examination is associated with a distinct pattern of worsening of osteoarthritis-related structural damage in the knee joint,” lead investigator Arya Haj-Mirzaian, MD, a radiologist and postdoctoral fellow at Johns Hopkins University, Baltimore, said in a press release.
However, HNs were also associated with less worsening of knee osteophytes, especially at the femoral end of the knee joint (aOR, 0.54; 95% CI, 0.31-0.95); the finding seemed to contradict the overall picture of worsening knee osteoarthritis with HNs.
“Although osteophytes are thought to be a late secondary sequel or compensatory repair mechanism in OA and indicator of advanced knee OA, less worsening in osteophytes’ score ... may propose that less ossification is involved in the pathophysiology of knee OA in the presence of HNs,” the investigators wrote. It’s a subject for future research.
Patients with HNs were older, more often female, and had a lower frequency for other knee OA risk factors, such as excessive body mass index and knee injury. Patients with gout were excluded.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Haj-Mirzaian A et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40811.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Heberden’s nodes may be an indicator of knee OA progression.
Major finding: There was more periarticular bone area expansion among patients with Heberden’s nodes at 2 years in the knee joint (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.83).
Study details: A substudy of 575 participants in the Osteoarthritis Initiative cohort
Disclosures: There was no external funding, and the investigators reported no disclosures.
Source: Haj-Mirzaian A et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40811.
Knee pathologies, including multiple meniscal tears, predict accelerated OA
Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.
The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.
“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.
The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.
Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.
Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.
Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.
At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.
Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.
Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).
“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.
The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.
“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.
“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.
The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.
SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.
Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.
The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.
“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.
The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.
Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.
Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.
Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.
At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.
Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.
Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).
“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.
The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.
“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.
“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.
The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.
SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.
Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.
The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.
“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.
The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.
Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.
Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.
Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.
At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.
Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.
Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).
“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.
The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.
“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.
“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.
The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.
SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: One year before the knee OA index visit, more than 75% of patients with accelerated knee OA had meniscal damage in at least two regions.
Study details: The data come from 375 adults with typical knee OA, accelerated knee OA, or no knee OA in the longitudinal Osteoarthritis Initiative cohort study.
Disclosures: The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.
Source: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.
Canakinumab reduces arthroplasty rates
CHICAGO – Canakinumab, a human monoclonal antibody targeting interleukin-1 beta, was associated with an eye-popping 45% relative risk reduction in the rate of total knee or hip replacement in a prespecified secondary analysis of the landmark CANTOS trial, Matthias Schieker, MD, reported at the annual meeting of the American College of Rheumatology.
For the broader composite endpoint of all osteoarthritis-related adverse events, including new-onset OA or worsening of symptoms in those with OA at baseline, the relative risk reduction was 23% in patients randomized to canakinumab rather than placebo. For CANTOS participants who already had OA at baseline, the relative risk reduction was 31%, according to Dr. Schieker, who is head of the joint, bone, and tendon disease group at the Novartis Institute for Biomedical Research in Basel, Switzerland, and professor of regenerative medicine at the University of Munich.
CANTOS (the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) was designed as a massive phase 3 secondary cardiovascular prevention trial. It included 10,061 patients with a history of acute MI and an elevated high-sensitivity C-reactive protein (hsCRP) level of 2 mg/L or more who were randomized double blind to subcutaneous canakinumab at 50, 150, or 300 mg or placebo given once every 3 months. During a median 3.7 years of prospective follow-up, patients in the 150-mg group had a highly significant 17% reduction relative to placebo in the risk of the composite efficacy endpoint comprising cardiovascular death, MI, stroke, or hospitalization for unstable angina resulting in urgent coronary revascularization (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
Since this result was achieved with a 39% reduction in CRP, compared with placebo, and involved no lipid-lowering effect, it was hailed in the cardiology world as the long-awaited proof of the inflammatory hypothesis of atherosclerotic cardiovascular disease.
CANTOS has proved to be the gift that keeps on giving. Secondary analyses of the study data have found statistically significant reductions in the incidence of and mortality caused by lung cancer in the coronary disease patients on canakinumab, as well as a decreased risk of developing gout. Moreover, the CANTOS investigators, well aware that there are no approved therapies to prevent disease progression in OA, had the foresight to prospectively collect data on OA-related symptoms and outcomes.
At baseline, 15.6% of CANTOS participants had a history of OA. During follow-up, patients in that subgroup had a 3.4% incidence of total knee replacement or total hip replacement if they had been assigned to canakinumab, compared with a 6.3% incidence if they got placebo. In the full 10,000-plus CANTOS cohort, the arthroplasty rates were 0.8% and 1.4%, respectively.
The combined rate of OA-related adverse events in the full CANTOS cohort was 5.4% with canakinumab and 7.0% with placebo. In the subgroup with baseline OA, the rates were 14.5% and 20.8%.
Canakinumab is marketed by Novartis as Ilaris and is already approved for cryopyrin-associated periodic syndromes, familial Mediterranean fever, juvenile idiopathic arthritis, and other rare autoimmune inflammatory diseases. Based upon the positive primary outcomes of the CANTOS trial, Novartis applied to the Food and Drug Administration for a major expanded indication of the IL-1B inhibitor for cardiovascular risk reduction. However, the regulatory agency has turned down that bid.
Although the CANTOS OA-related outcomes data caused quite a stir at the meeting, Dr. Schieker said in an interview that the impressive findings didn’t really come as a surprise to him.
“I think everyone in the field has assumed that IL-1 plays a role in OA. That idea has been around for quite a long time, but until now no effects could be shown in OA. We were lucky to have an enriched population with elevated hsCRP that was so large and followed for so long that we could finally show these relative risk reductions,” he explained.
SOURCE: Schieker M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 445.
CHICAGO – Canakinumab, a human monoclonal antibody targeting interleukin-1 beta, was associated with an eye-popping 45% relative risk reduction in the rate of total knee or hip replacement in a prespecified secondary analysis of the landmark CANTOS trial, Matthias Schieker, MD, reported at the annual meeting of the American College of Rheumatology.
For the broader composite endpoint of all osteoarthritis-related adverse events, including new-onset OA or worsening of symptoms in those with OA at baseline, the relative risk reduction was 23% in patients randomized to canakinumab rather than placebo. For CANTOS participants who already had OA at baseline, the relative risk reduction was 31%, according to Dr. Schieker, who is head of the joint, bone, and tendon disease group at the Novartis Institute for Biomedical Research in Basel, Switzerland, and professor of regenerative medicine at the University of Munich.
CANTOS (the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) was designed as a massive phase 3 secondary cardiovascular prevention trial. It included 10,061 patients with a history of acute MI and an elevated high-sensitivity C-reactive protein (hsCRP) level of 2 mg/L or more who were randomized double blind to subcutaneous canakinumab at 50, 150, or 300 mg or placebo given once every 3 months. During a median 3.7 years of prospective follow-up, patients in the 150-mg group had a highly significant 17% reduction relative to placebo in the risk of the composite efficacy endpoint comprising cardiovascular death, MI, stroke, or hospitalization for unstable angina resulting in urgent coronary revascularization (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
Since this result was achieved with a 39% reduction in CRP, compared with placebo, and involved no lipid-lowering effect, it was hailed in the cardiology world as the long-awaited proof of the inflammatory hypothesis of atherosclerotic cardiovascular disease.
CANTOS has proved to be the gift that keeps on giving. Secondary analyses of the study data have found statistically significant reductions in the incidence of and mortality caused by lung cancer in the coronary disease patients on canakinumab, as well as a decreased risk of developing gout. Moreover, the CANTOS investigators, well aware that there are no approved therapies to prevent disease progression in OA, had the foresight to prospectively collect data on OA-related symptoms and outcomes.
At baseline, 15.6% of CANTOS participants had a history of OA. During follow-up, patients in that subgroup had a 3.4% incidence of total knee replacement or total hip replacement if they had been assigned to canakinumab, compared with a 6.3% incidence if they got placebo. In the full 10,000-plus CANTOS cohort, the arthroplasty rates were 0.8% and 1.4%, respectively.
The combined rate of OA-related adverse events in the full CANTOS cohort was 5.4% with canakinumab and 7.0% with placebo. In the subgroup with baseline OA, the rates were 14.5% and 20.8%.
Canakinumab is marketed by Novartis as Ilaris and is already approved for cryopyrin-associated periodic syndromes, familial Mediterranean fever, juvenile idiopathic arthritis, and other rare autoimmune inflammatory diseases. Based upon the positive primary outcomes of the CANTOS trial, Novartis applied to the Food and Drug Administration for a major expanded indication of the IL-1B inhibitor for cardiovascular risk reduction. However, the regulatory agency has turned down that bid.
Although the CANTOS OA-related outcomes data caused quite a stir at the meeting, Dr. Schieker said in an interview that the impressive findings didn’t really come as a surprise to him.
“I think everyone in the field has assumed that IL-1 plays a role in OA. That idea has been around for quite a long time, but until now no effects could be shown in OA. We were lucky to have an enriched population with elevated hsCRP that was so large and followed for so long that we could finally show these relative risk reductions,” he explained.
SOURCE: Schieker M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 445.
CHICAGO – Canakinumab, a human monoclonal antibody targeting interleukin-1 beta, was associated with an eye-popping 45% relative risk reduction in the rate of total knee or hip replacement in a prespecified secondary analysis of the landmark CANTOS trial, Matthias Schieker, MD, reported at the annual meeting of the American College of Rheumatology.
For the broader composite endpoint of all osteoarthritis-related adverse events, including new-onset OA or worsening of symptoms in those with OA at baseline, the relative risk reduction was 23% in patients randomized to canakinumab rather than placebo. For CANTOS participants who already had OA at baseline, the relative risk reduction was 31%, according to Dr. Schieker, who is head of the joint, bone, and tendon disease group at the Novartis Institute for Biomedical Research in Basel, Switzerland, and professor of regenerative medicine at the University of Munich.
CANTOS (the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) was designed as a massive phase 3 secondary cardiovascular prevention trial. It included 10,061 patients with a history of acute MI and an elevated high-sensitivity C-reactive protein (hsCRP) level of 2 mg/L or more who were randomized double blind to subcutaneous canakinumab at 50, 150, or 300 mg or placebo given once every 3 months. During a median 3.7 years of prospective follow-up, patients in the 150-mg group had a highly significant 17% reduction relative to placebo in the risk of the composite efficacy endpoint comprising cardiovascular death, MI, stroke, or hospitalization for unstable angina resulting in urgent coronary revascularization (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
Since this result was achieved with a 39% reduction in CRP, compared with placebo, and involved no lipid-lowering effect, it was hailed in the cardiology world as the long-awaited proof of the inflammatory hypothesis of atherosclerotic cardiovascular disease.
CANTOS has proved to be the gift that keeps on giving. Secondary analyses of the study data have found statistically significant reductions in the incidence of and mortality caused by lung cancer in the coronary disease patients on canakinumab, as well as a decreased risk of developing gout. Moreover, the CANTOS investigators, well aware that there are no approved therapies to prevent disease progression in OA, had the foresight to prospectively collect data on OA-related symptoms and outcomes.
At baseline, 15.6% of CANTOS participants had a history of OA. During follow-up, patients in that subgroup had a 3.4% incidence of total knee replacement or total hip replacement if they had been assigned to canakinumab, compared with a 6.3% incidence if they got placebo. In the full 10,000-plus CANTOS cohort, the arthroplasty rates were 0.8% and 1.4%, respectively.
The combined rate of OA-related adverse events in the full CANTOS cohort was 5.4% with canakinumab and 7.0% with placebo. In the subgroup with baseline OA, the rates were 14.5% and 20.8%.
Canakinumab is marketed by Novartis as Ilaris and is already approved for cryopyrin-associated periodic syndromes, familial Mediterranean fever, juvenile idiopathic arthritis, and other rare autoimmune inflammatory diseases. Based upon the positive primary outcomes of the CANTOS trial, Novartis applied to the Food and Drug Administration for a major expanded indication of the IL-1B inhibitor for cardiovascular risk reduction. However, the regulatory agency has turned down that bid.
Although the CANTOS OA-related outcomes data caused quite a stir at the meeting, Dr. Schieker said in an interview that the impressive findings didn’t really come as a surprise to him.
“I think everyone in the field has assumed that IL-1 plays a role in OA. That idea has been around for quite a long time, but until now no effects could be shown in OA. We were lucky to have an enriched population with elevated hsCRP that was so large and followed for so long that we could finally show these relative risk reductions,” he explained.
SOURCE: Schieker M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 445.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Patients on the IL-1B inhibitor canakinumab for secondary cardiovascular prevention also experienced a 45% risk reduction in total knee or total hip replacement, compared with placebo.
Study details: This was a prespecified secondary analysis of OA-related outcomes in the 10,061 participants in the randomized, double-blind CANTOS trial.
Disclosures: The presenter is an employee of Novartis, which markets canakinumab and sponsored CANTOS.
Source: Schieker M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 445.