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For MD-IQ on Family Practice News, but a regular topic for Rheumatology News
Targeting inactivity, mood, and cognition could be key to reducing OA mortality
LIVERPOOL, ENGLAND – Osteoarthritis is associated with an increased risk in mortality, but three factors – inactivity, low mood, and cognitive ability – could be important targets to reduce this risk, according to the results of a study presented at the World Congress on Osteoarthritis.
“There’s recently been increasing interest in whether osteoarthritis (OA) is associated with mortality as the literature has failed to find a consistent link,” said Simran Parmar, a third-year medical student at Keele University, Newcastle-Under-Lyme, U.K.
Three years later, data from another study (BMJ. 2011;342:d1165) suggested an increased risk, with standardized mortality ratios calculated to be 1.55 for all-cause mortality and 1.71 for cardiovascular-specific mortality when comparing those with OA to those without OA in the general population.
However, more recent meta-analyses, performed in 2016, have failed to show a relationship between mortality and OA (Semin Arthritis Rheum. 2016;46[2]:160–7; Sci Rep. 2016;6:24393).
“This could be because of heterogeneity among the studies,” Mr. Parmar reasoned, adding that there was still an unclear relationship between OA and mortality.
So the aim of the current study was not only to take another look at the association to determine its strength but also to see what factors might be mediating the association in order to perhaps explain why OA might be associated with an increased risk of death.
The analysis used data on more than 8,000 individuals participating in the NorStOP (North Staffordshire Osteoarthritis Project). This is a large, population-based, prospective cohort initiated in 2002 that includes adults aged 50 years or older who are registered at any of six general practices.
At baseline, the mean age of participants was 65 years, 51% were female, and just under 30% had OA. During 10 years of follow-up, 1,188 (14.7%) participants died.
Osteoarthritis was significantly associated with mortality in both unadjusted and adjusted analyses.
“For the average person presenting to general practice in North Staffordshire, there’s a 39.4% increased risk of mortality if they have osteoarthritis compared to if they don’t,” Mr. Parmar said.
After adjustment for potential confounding factors, such as age, NSAID use, and common comorbidities, the increased mortality risk remained, with around a 15% increased risk of death for those with OA versus those without.
“We proposed six different mediators of this relationship,” Mr. Parmar said. These were depression, anxiety, low walking frequency, cognitive impairment, insomnia, and obesity. “The reason we chose these is because they can be targets for therapy in primary care.”
Three mediators significantly affected the relationship: low walking frequency, depression, and cognitive impairment; the respective hazard ratios and 95% confidence intervals were 1.12 (1.09-1.15), 1.11 (1.08-1.15), and 1.06 (1.03-1.09).
“This tells us that these could possibly be on the pathway between osteoarthritis and mortality, and this could provide further evidence that they could be used for targeted therapy of osteoarthritis,” Mr. Parmar suggested.
“This type of mediation analysis has not been done in the osteoarthritis field before,” Mr. Parmar observed. He conceded that the mediators found might actually have contributed to the development of OA and that pain interference used in the definition of OA could have been caused by other factors.
Nevertheless, these data suggest that there may be actionable factors that could be used in primary care to reduce mortality in OA.
Mr. Parmar suggested that “encouraging physical activity and considering the impact of comorbidities can help reduce the risk of mortality in adults with osteoarthritis.”
The study was funded by Arthritis Research UK, the North Staffordshire Primary Care Consortium, and the Medical Research Council. Mr. Parmar had no conflicts of interest to disclose.
SOURCE: Parmar S et al. Osteoarthritis Cartilage. 2018;26(1):S14-15.
LIVERPOOL, ENGLAND – Osteoarthritis is associated with an increased risk in mortality, but three factors – inactivity, low mood, and cognitive ability – could be important targets to reduce this risk, according to the results of a study presented at the World Congress on Osteoarthritis.
“There’s recently been increasing interest in whether osteoarthritis (OA) is associated with mortality as the literature has failed to find a consistent link,” said Simran Parmar, a third-year medical student at Keele University, Newcastle-Under-Lyme, U.K.
Three years later, data from another study (BMJ. 2011;342:d1165) suggested an increased risk, with standardized mortality ratios calculated to be 1.55 for all-cause mortality and 1.71 for cardiovascular-specific mortality when comparing those with OA to those without OA in the general population.
However, more recent meta-analyses, performed in 2016, have failed to show a relationship between mortality and OA (Semin Arthritis Rheum. 2016;46[2]:160–7; Sci Rep. 2016;6:24393).
“This could be because of heterogeneity among the studies,” Mr. Parmar reasoned, adding that there was still an unclear relationship between OA and mortality.
So the aim of the current study was not only to take another look at the association to determine its strength but also to see what factors might be mediating the association in order to perhaps explain why OA might be associated with an increased risk of death.
The analysis used data on more than 8,000 individuals participating in the NorStOP (North Staffordshire Osteoarthritis Project). This is a large, population-based, prospective cohort initiated in 2002 that includes adults aged 50 years or older who are registered at any of six general practices.
At baseline, the mean age of participants was 65 years, 51% were female, and just under 30% had OA. During 10 years of follow-up, 1,188 (14.7%) participants died.
Osteoarthritis was significantly associated with mortality in both unadjusted and adjusted analyses.
“For the average person presenting to general practice in North Staffordshire, there’s a 39.4% increased risk of mortality if they have osteoarthritis compared to if they don’t,” Mr. Parmar said.
After adjustment for potential confounding factors, such as age, NSAID use, and common comorbidities, the increased mortality risk remained, with around a 15% increased risk of death for those with OA versus those without.
“We proposed six different mediators of this relationship,” Mr. Parmar said. These were depression, anxiety, low walking frequency, cognitive impairment, insomnia, and obesity. “The reason we chose these is because they can be targets for therapy in primary care.”
Three mediators significantly affected the relationship: low walking frequency, depression, and cognitive impairment; the respective hazard ratios and 95% confidence intervals were 1.12 (1.09-1.15), 1.11 (1.08-1.15), and 1.06 (1.03-1.09).
“This tells us that these could possibly be on the pathway between osteoarthritis and mortality, and this could provide further evidence that they could be used for targeted therapy of osteoarthritis,” Mr. Parmar suggested.
“This type of mediation analysis has not been done in the osteoarthritis field before,” Mr. Parmar observed. He conceded that the mediators found might actually have contributed to the development of OA and that pain interference used in the definition of OA could have been caused by other factors.
Nevertheless, these data suggest that there may be actionable factors that could be used in primary care to reduce mortality in OA.
Mr. Parmar suggested that “encouraging physical activity and considering the impact of comorbidities can help reduce the risk of mortality in adults with osteoarthritis.”
The study was funded by Arthritis Research UK, the North Staffordshire Primary Care Consortium, and the Medical Research Council. Mr. Parmar had no conflicts of interest to disclose.
SOURCE: Parmar S et al. Osteoarthritis Cartilage. 2018;26(1):S14-15.
LIVERPOOL, ENGLAND – Osteoarthritis is associated with an increased risk in mortality, but three factors – inactivity, low mood, and cognitive ability – could be important targets to reduce this risk, according to the results of a study presented at the World Congress on Osteoarthritis.
“There’s recently been increasing interest in whether osteoarthritis (OA) is associated with mortality as the literature has failed to find a consistent link,” said Simran Parmar, a third-year medical student at Keele University, Newcastle-Under-Lyme, U.K.
Three years later, data from another study (BMJ. 2011;342:d1165) suggested an increased risk, with standardized mortality ratios calculated to be 1.55 for all-cause mortality and 1.71 for cardiovascular-specific mortality when comparing those with OA to those without OA in the general population.
However, more recent meta-analyses, performed in 2016, have failed to show a relationship between mortality and OA (Semin Arthritis Rheum. 2016;46[2]:160–7; Sci Rep. 2016;6:24393).
“This could be because of heterogeneity among the studies,” Mr. Parmar reasoned, adding that there was still an unclear relationship between OA and mortality.
So the aim of the current study was not only to take another look at the association to determine its strength but also to see what factors might be mediating the association in order to perhaps explain why OA might be associated with an increased risk of death.
The analysis used data on more than 8,000 individuals participating in the NorStOP (North Staffordshire Osteoarthritis Project). This is a large, population-based, prospective cohort initiated in 2002 that includes adults aged 50 years or older who are registered at any of six general practices.
At baseline, the mean age of participants was 65 years, 51% were female, and just under 30% had OA. During 10 years of follow-up, 1,188 (14.7%) participants died.
Osteoarthritis was significantly associated with mortality in both unadjusted and adjusted analyses.
“For the average person presenting to general practice in North Staffordshire, there’s a 39.4% increased risk of mortality if they have osteoarthritis compared to if they don’t,” Mr. Parmar said.
After adjustment for potential confounding factors, such as age, NSAID use, and common comorbidities, the increased mortality risk remained, with around a 15% increased risk of death for those with OA versus those without.
“We proposed six different mediators of this relationship,” Mr. Parmar said. These were depression, anxiety, low walking frequency, cognitive impairment, insomnia, and obesity. “The reason we chose these is because they can be targets for therapy in primary care.”
Three mediators significantly affected the relationship: low walking frequency, depression, and cognitive impairment; the respective hazard ratios and 95% confidence intervals were 1.12 (1.09-1.15), 1.11 (1.08-1.15), and 1.06 (1.03-1.09).
“This tells us that these could possibly be on the pathway between osteoarthritis and mortality, and this could provide further evidence that they could be used for targeted therapy of osteoarthritis,” Mr. Parmar suggested.
“This type of mediation analysis has not been done in the osteoarthritis field before,” Mr. Parmar observed. He conceded that the mediators found might actually have contributed to the development of OA and that pain interference used in the definition of OA could have been caused by other factors.
Nevertheless, these data suggest that there may be actionable factors that could be used in primary care to reduce mortality in OA.
Mr. Parmar suggested that “encouraging physical activity and considering the impact of comorbidities can help reduce the risk of mortality in adults with osteoarthritis.”
The study was funded by Arthritis Research UK, the North Staffordshire Primary Care Consortium, and the Medical Research Council. Mr. Parmar had no conflicts of interest to disclose.
SOURCE: Parmar S et al. Osteoarthritis Cartilage. 2018;26(1):S14-15.
REPORTING FROM OARSI 2018
Key clinical point:
Major finding: OA is associated with a 15% increased risk of mortality in the general population.
Study details: A large, prospective cohort study that included more than 8,000 adults older than 50 years in the general population who participated.
Disclosures: The study was funded by Arthritis Research UK, the North Staffordshire Primary Care Consortium, and the Medical Research Council. Mr. Parmar had no conflicts of interest to disclose.
Source: Parmar S et al. Osteoarthritis Cartilage. 2018;26(1):S14-15.
FDA advisory committee votes to recommend update to celecoxib safety labeling
SILVER SPRING, MD. – An FDA advisory committee voted (15 yes, 5 no, 1 abstention) to update the safety information in the label of celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), for use in patients with osteoarthritis (OA) and rheumatoid arthritis, on the basis of results of the PRECISION trial.
A Joint Meeting ofthe Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee was convened April 24-25 to address two issues, the first being the consideration of Pfizer’s application for celecoxib and the second, to assess the safety of celecoxib and other common NSAIDs like ibuprofen and naproxen.
The randomized controlled PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial compared celecoxib, naproxen, and ibuprofen and their cardiovascular outcomes. The PRECISION trial was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that the rates of cardiovascular events (cardiovascular death, myocardial infarction, or stroke) were 2.3% with celecoxib, 2.5% with naproxen, and 2.7% with ibuprofen during a follow-up approaching 3 years, showing noninferiority for celecoxib.
In a post hoc analysis presented by Steven Nissen, MD, patients taking ibuprofen and naproxen experienced adjudicated cardiovascular, GI, or renal events 28% and 15% more than did patients taking celecoxib.
The results of the study could inform clinical strategy, said Dr. Nissen, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “For arthritis patients who require NSAIDs to achieve an acceptable quality of life, particularly those at high cardiovascular, GI, or renal risk, the PRECISION trial suggests that a clinical strategy of starting patients on celecoxib 200 mg daily may be the safest approach, reserving full therapeutic doses of ibuprofen and naproxen for patients who do not respond to celecoxib."
SILVER SPRING, MD. – An FDA advisory committee voted (15 yes, 5 no, 1 abstention) to update the safety information in the label of celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), for use in patients with osteoarthritis (OA) and rheumatoid arthritis, on the basis of results of the PRECISION trial.
A Joint Meeting ofthe Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee was convened April 24-25 to address two issues, the first being the consideration of Pfizer’s application for celecoxib and the second, to assess the safety of celecoxib and other common NSAIDs like ibuprofen and naproxen.
The randomized controlled PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial compared celecoxib, naproxen, and ibuprofen and their cardiovascular outcomes. The PRECISION trial was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that the rates of cardiovascular events (cardiovascular death, myocardial infarction, or stroke) were 2.3% with celecoxib, 2.5% with naproxen, and 2.7% with ibuprofen during a follow-up approaching 3 years, showing noninferiority for celecoxib.
In a post hoc analysis presented by Steven Nissen, MD, patients taking ibuprofen and naproxen experienced adjudicated cardiovascular, GI, or renal events 28% and 15% more than did patients taking celecoxib.
The results of the study could inform clinical strategy, said Dr. Nissen, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “For arthritis patients who require NSAIDs to achieve an acceptable quality of life, particularly those at high cardiovascular, GI, or renal risk, the PRECISION trial suggests that a clinical strategy of starting patients on celecoxib 200 mg daily may be the safest approach, reserving full therapeutic doses of ibuprofen and naproxen for patients who do not respond to celecoxib."
SILVER SPRING, MD. – An FDA advisory committee voted (15 yes, 5 no, 1 abstention) to update the safety information in the label of celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), for use in patients with osteoarthritis (OA) and rheumatoid arthritis, on the basis of results of the PRECISION trial.
A Joint Meeting ofthe Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee was convened April 24-25 to address two issues, the first being the consideration of Pfizer’s application for celecoxib and the second, to assess the safety of celecoxib and other common NSAIDs like ibuprofen and naproxen.
The randomized controlled PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial compared celecoxib, naproxen, and ibuprofen and their cardiovascular outcomes. The PRECISION trial was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that the rates of cardiovascular events (cardiovascular death, myocardial infarction, or stroke) were 2.3% with celecoxib, 2.5% with naproxen, and 2.7% with ibuprofen during a follow-up approaching 3 years, showing noninferiority for celecoxib.
In a post hoc analysis presented by Steven Nissen, MD, patients taking ibuprofen and naproxen experienced adjudicated cardiovascular, GI, or renal events 28% and 15% more than did patients taking celecoxib.
The results of the study could inform clinical strategy, said Dr. Nissen, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “For arthritis patients who require NSAIDs to achieve an acceptable quality of life, particularly those at high cardiovascular, GI, or renal risk, the PRECISION trial suggests that a clinical strategy of starting patients on celecoxib 200 mg daily may be the safest approach, reserving full therapeutic doses of ibuprofen and naproxen for patients who do not respond to celecoxib."
REPORTING FROM AN FDA ADVISORY COMMITTEE MEETING
Arthritis limits physical activity the most in the South
“Physical activity is a proven strategy for managing arthritis symptoms,” but 35% of Americans with arthritis do not participate in any such activities or exercise, according to investigators who analyzed data from a national survey of more than 440,000 adults.
The low rates of inactivity in the western half of the country were topped by California’s 23.1% and South Dakota’s 23.4%, with Oregon (24.0%) and Wisconsin (24.6%) not too far behind, Dr. Barbour and his associates said based on data for 441,456 adults aged 18 years and older who were interviewed for the Behavioral Risk Factor Surveillance System.
Overall prevalence rates show that arthritis has the greatest effect in southern states, which, in addition to high inactivity, had more arthritis-attributable severe joint pain, more arthritis-attributable social participation restriction, and less leisure-time walking among adults with arthritis. This information, the investigators suggested, may help public health professionals “to better understand and target evidence-based nonpharmaceutical interventions, such as arthritis self-management education and physical activity.”
SOURCE: Barbour KE et al. MMWR Surveill Summ. 2018 Mar 16;67(4):1-28.
“Physical activity is a proven strategy for managing arthritis symptoms,” but 35% of Americans with arthritis do not participate in any such activities or exercise, according to investigators who analyzed data from a national survey of more than 440,000 adults.
The low rates of inactivity in the western half of the country were topped by California’s 23.1% and South Dakota’s 23.4%, with Oregon (24.0%) and Wisconsin (24.6%) not too far behind, Dr. Barbour and his associates said based on data for 441,456 adults aged 18 years and older who were interviewed for the Behavioral Risk Factor Surveillance System.
Overall prevalence rates show that arthritis has the greatest effect in southern states, which, in addition to high inactivity, had more arthritis-attributable severe joint pain, more arthritis-attributable social participation restriction, and less leisure-time walking among adults with arthritis. This information, the investigators suggested, may help public health professionals “to better understand and target evidence-based nonpharmaceutical interventions, such as arthritis self-management education and physical activity.”
SOURCE: Barbour KE et al. MMWR Surveill Summ. 2018 Mar 16;67(4):1-28.
“Physical activity is a proven strategy for managing arthritis symptoms,” but 35% of Americans with arthritis do not participate in any such activities or exercise, according to investigators who analyzed data from a national survey of more than 440,000 adults.
The low rates of inactivity in the western half of the country were topped by California’s 23.1% and South Dakota’s 23.4%, with Oregon (24.0%) and Wisconsin (24.6%) not too far behind, Dr. Barbour and his associates said based on data for 441,456 adults aged 18 years and older who were interviewed for the Behavioral Risk Factor Surveillance System.
Overall prevalence rates show that arthritis has the greatest effect in southern states, which, in addition to high inactivity, had more arthritis-attributable severe joint pain, more arthritis-attributable social participation restriction, and less leisure-time walking among adults with arthritis. This information, the investigators suggested, may help public health professionals “to better understand and target evidence-based nonpharmaceutical interventions, such as arthritis self-management education and physical activity.”
SOURCE: Barbour KE et al. MMWR Surveill Summ. 2018 Mar 16;67(4):1-28.
FROM MMWR SURVEILLANCE SUMMARIES
Intramuscular steroid injection reduced hip OA pain up to 12 weeks
Systemic treatment with an intramuscular glucocorticoid injection is effective, compared with placebo, in reducing pain in people with hip osteoarthritis for up to 12 weeks, a double-blinded, placebo-controlled, randomized trial suggests.
However, the study found benefit with intramuscular (IM) glucocorticoid injection at 2 weeks only when patients were at rest, and did not find any significant benefit with the injection in reducing pain while walking or in reducing Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale scores. The report was published in Annals of the Rheumatic Diseases.
The multicenter, double-blinded, superiority trial randomized 106 patients with painful hip OA who were not responding to oral analgesics to either 40 mg triamcinolone acetate (n = 52) or placebo injection (n = 54) into the gluteus muscle. Overall, 73 patients (68%) were women, and the average age of the cohort was 64 years. Hip OA symptoms had occurred for at least 1 year in 70% of the patients.
The study’s three primary outcomes of hip pain severity 2 weeks after the injection on a 0-10 scale at rest and during walking and on the WOMAC pain subscale revealed inconsistent results with the treatment.
At the 2-week follow-up, patients who had received the IM glucocorticoid injection had a significant and clinically relevant difference in hip pain at rest (between-group difference = –1.3; 95% confidence interval, –2.3 to –0.3; P = .01). But at this time point there were no significant associations between glucocorticoid injection and hip pain during walking (difference = –0.9; 95% CI, –1.9 to 0.1; P = .07) and WOMAC pain subscale score (difference = –6.1; 95% CI, –13.4 to 1.2; P = .10), the researchers reported.
At 2-week follow-up, recipients of the glucocorticoid injection were significantly more likely to perceive improvement (relative risk = 1.7; 95% CI, 1.1 to 2.7; P = .02) or achieve OMERACT-OARSI level of response (RR = 2.0; 95% CI, 1.1 to 3.6; P = .03).
The authors described this finding as “surprising,” speculating that the 7-point Likert scale used to measure perceived improvement could have resulted in less power.
Nineteen patients in the glucocorticoid group reported 27 nonserious adverse events, compared with 13 patients in the placebo group who reported 18 adverse events.
The authors said the greatest effects of the glucocorticoid injection were seen at 4- to 12-week follow-up (the secondary outcomes of the study), instead of at the 2-week follow-up. For example, at 4-week follow-up, the glucocorticoid injection was associated with a significant hip pain reduction at rest (between-group difference = –1.2; 95% CI, –2.1 to –0.2; P = .01) and during walking (difference = –1.1; 95% CI, –2.0 to –0.2; P = .01). At 6 weeks, the corresponding figures for hip pain reduction were –1.4 at rest (95% CI, –2.4 to –0.5; P = .005) and –1.4 while walking (95% CI, –2.3 to –0.4; P = .004). The between-group differences were still significant at 12 weeks while at rest (difference = –1.2; 95% CI, –2.3 to –0.2; P = .02) and during walking (difference = –1.3; 95% CI, –2.2 to –0.3; P = .01).
Significant differences in favor of the glucocorticoid injection overall occurred on the WOMAC subscale scores for pain, function, and stiffness, as well as total Hip disability and Osteoarthritis Outcome Score for pain and total, intermittent, and constant pain measures on the Intermittent and Constant Osteoarthritis Pain scale. At 12 weeks, the between-group difference on the WOMAC total score was –9.4 (95% CI, –17.8 to –0.9; P = .03).
The researchers said it was surprising that hip pain reduction after IM glucocorticoid injection was still present at a similar degree at 12 weeks since previous studies had shown the effect usually peaked after 1-3 weeks.
“Our findings should be replicated in future research,” they said.
“An IM glucocorticoid injection showed effectiveness in patients with hip OA on one of the three primary outcomes at a 2 weeks post injection ... The effect is probably clinically relevant,” the authors concluded.
The investigators noted that in clinical practice patients are sometimes offered multiple injections per year, whereas in the current study patients received only one injection. There has also been concern that intra-articular glucocorticoid injections could cause toxicity to chondrocytes and potentially lead to OA progression, but the effect of a single IM injection is unknown.
Financial support for the study came from the Dutch Arthritis Foundation and the NutsOhra fund. Two of the authors reported receiving grants from several pharmaceutical companies, research consortia, and foundations.
SOURCE: Dorleijn D et al. Ann Rheum Dis. 2018 March 7. doi: 10.1136/annrheumdis-2017-212628
Systemic treatment with an intramuscular glucocorticoid injection is effective, compared with placebo, in reducing pain in people with hip osteoarthritis for up to 12 weeks, a double-blinded, placebo-controlled, randomized trial suggests.
However, the study found benefit with intramuscular (IM) glucocorticoid injection at 2 weeks only when patients were at rest, and did not find any significant benefit with the injection in reducing pain while walking or in reducing Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale scores. The report was published in Annals of the Rheumatic Diseases.
The multicenter, double-blinded, superiority trial randomized 106 patients with painful hip OA who were not responding to oral analgesics to either 40 mg triamcinolone acetate (n = 52) or placebo injection (n = 54) into the gluteus muscle. Overall, 73 patients (68%) were women, and the average age of the cohort was 64 years. Hip OA symptoms had occurred for at least 1 year in 70% of the patients.
The study’s three primary outcomes of hip pain severity 2 weeks after the injection on a 0-10 scale at rest and during walking and on the WOMAC pain subscale revealed inconsistent results with the treatment.
At the 2-week follow-up, patients who had received the IM glucocorticoid injection had a significant and clinically relevant difference in hip pain at rest (between-group difference = –1.3; 95% confidence interval, –2.3 to –0.3; P = .01). But at this time point there were no significant associations between glucocorticoid injection and hip pain during walking (difference = –0.9; 95% CI, –1.9 to 0.1; P = .07) and WOMAC pain subscale score (difference = –6.1; 95% CI, –13.4 to 1.2; P = .10), the researchers reported.
At 2-week follow-up, recipients of the glucocorticoid injection were significantly more likely to perceive improvement (relative risk = 1.7; 95% CI, 1.1 to 2.7; P = .02) or achieve OMERACT-OARSI level of response (RR = 2.0; 95% CI, 1.1 to 3.6; P = .03).
The authors described this finding as “surprising,” speculating that the 7-point Likert scale used to measure perceived improvement could have resulted in less power.
Nineteen patients in the glucocorticoid group reported 27 nonserious adverse events, compared with 13 patients in the placebo group who reported 18 adverse events.
The authors said the greatest effects of the glucocorticoid injection were seen at 4- to 12-week follow-up (the secondary outcomes of the study), instead of at the 2-week follow-up. For example, at 4-week follow-up, the glucocorticoid injection was associated with a significant hip pain reduction at rest (between-group difference = –1.2; 95% CI, –2.1 to –0.2; P = .01) and during walking (difference = –1.1; 95% CI, –2.0 to –0.2; P = .01). At 6 weeks, the corresponding figures for hip pain reduction were –1.4 at rest (95% CI, –2.4 to –0.5; P = .005) and –1.4 while walking (95% CI, –2.3 to –0.4; P = .004). The between-group differences were still significant at 12 weeks while at rest (difference = –1.2; 95% CI, –2.3 to –0.2; P = .02) and during walking (difference = –1.3; 95% CI, –2.2 to –0.3; P = .01).
Significant differences in favor of the glucocorticoid injection overall occurred on the WOMAC subscale scores for pain, function, and stiffness, as well as total Hip disability and Osteoarthritis Outcome Score for pain and total, intermittent, and constant pain measures on the Intermittent and Constant Osteoarthritis Pain scale. At 12 weeks, the between-group difference on the WOMAC total score was –9.4 (95% CI, –17.8 to –0.9; P = .03).
The researchers said it was surprising that hip pain reduction after IM glucocorticoid injection was still present at a similar degree at 12 weeks since previous studies had shown the effect usually peaked after 1-3 weeks.
“Our findings should be replicated in future research,” they said.
“An IM glucocorticoid injection showed effectiveness in patients with hip OA on one of the three primary outcomes at a 2 weeks post injection ... The effect is probably clinically relevant,” the authors concluded.
The investigators noted that in clinical practice patients are sometimes offered multiple injections per year, whereas in the current study patients received only one injection. There has also been concern that intra-articular glucocorticoid injections could cause toxicity to chondrocytes and potentially lead to OA progression, but the effect of a single IM injection is unknown.
Financial support for the study came from the Dutch Arthritis Foundation and the NutsOhra fund. Two of the authors reported receiving grants from several pharmaceutical companies, research consortia, and foundations.
SOURCE: Dorleijn D et al. Ann Rheum Dis. 2018 March 7. doi: 10.1136/annrheumdis-2017-212628
Systemic treatment with an intramuscular glucocorticoid injection is effective, compared with placebo, in reducing pain in people with hip osteoarthritis for up to 12 weeks, a double-blinded, placebo-controlled, randomized trial suggests.
However, the study found benefit with intramuscular (IM) glucocorticoid injection at 2 weeks only when patients were at rest, and did not find any significant benefit with the injection in reducing pain while walking or in reducing Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale scores. The report was published in Annals of the Rheumatic Diseases.
The multicenter, double-blinded, superiority trial randomized 106 patients with painful hip OA who were not responding to oral analgesics to either 40 mg triamcinolone acetate (n = 52) or placebo injection (n = 54) into the gluteus muscle. Overall, 73 patients (68%) were women, and the average age of the cohort was 64 years. Hip OA symptoms had occurred for at least 1 year in 70% of the patients.
The study’s three primary outcomes of hip pain severity 2 weeks after the injection on a 0-10 scale at rest and during walking and on the WOMAC pain subscale revealed inconsistent results with the treatment.
At the 2-week follow-up, patients who had received the IM glucocorticoid injection had a significant and clinically relevant difference in hip pain at rest (between-group difference = –1.3; 95% confidence interval, –2.3 to –0.3; P = .01). But at this time point there were no significant associations between glucocorticoid injection and hip pain during walking (difference = –0.9; 95% CI, –1.9 to 0.1; P = .07) and WOMAC pain subscale score (difference = –6.1; 95% CI, –13.4 to 1.2; P = .10), the researchers reported.
At 2-week follow-up, recipients of the glucocorticoid injection were significantly more likely to perceive improvement (relative risk = 1.7; 95% CI, 1.1 to 2.7; P = .02) or achieve OMERACT-OARSI level of response (RR = 2.0; 95% CI, 1.1 to 3.6; P = .03).
The authors described this finding as “surprising,” speculating that the 7-point Likert scale used to measure perceived improvement could have resulted in less power.
Nineteen patients in the glucocorticoid group reported 27 nonserious adverse events, compared with 13 patients in the placebo group who reported 18 adverse events.
The authors said the greatest effects of the glucocorticoid injection were seen at 4- to 12-week follow-up (the secondary outcomes of the study), instead of at the 2-week follow-up. For example, at 4-week follow-up, the glucocorticoid injection was associated with a significant hip pain reduction at rest (between-group difference = –1.2; 95% CI, –2.1 to –0.2; P = .01) and during walking (difference = –1.1; 95% CI, –2.0 to –0.2; P = .01). At 6 weeks, the corresponding figures for hip pain reduction were –1.4 at rest (95% CI, –2.4 to –0.5; P = .005) and –1.4 while walking (95% CI, –2.3 to –0.4; P = .004). The between-group differences were still significant at 12 weeks while at rest (difference = –1.2; 95% CI, –2.3 to –0.2; P = .02) and during walking (difference = –1.3; 95% CI, –2.2 to –0.3; P = .01).
Significant differences in favor of the glucocorticoid injection overall occurred on the WOMAC subscale scores for pain, function, and stiffness, as well as total Hip disability and Osteoarthritis Outcome Score for pain and total, intermittent, and constant pain measures on the Intermittent and Constant Osteoarthritis Pain scale. At 12 weeks, the between-group difference on the WOMAC total score was –9.4 (95% CI, –17.8 to –0.9; P = .03).
The researchers said it was surprising that hip pain reduction after IM glucocorticoid injection was still present at a similar degree at 12 weeks since previous studies had shown the effect usually peaked after 1-3 weeks.
“Our findings should be replicated in future research,” they said.
“An IM glucocorticoid injection showed effectiveness in patients with hip OA on one of the three primary outcomes at a 2 weeks post injection ... The effect is probably clinically relevant,” the authors concluded.
The investigators noted that in clinical practice patients are sometimes offered multiple injections per year, whereas in the current study patients received only one injection. There has also been concern that intra-articular glucocorticoid injections could cause toxicity to chondrocytes and potentially lead to OA progression, but the effect of a single IM injection is unknown.
Financial support for the study came from the Dutch Arthritis Foundation and the NutsOhra fund. Two of the authors reported receiving grants from several pharmaceutical companies, research consortia, and foundations.
SOURCE: Dorleijn D et al. Ann Rheum Dis. 2018 March 7. doi: 10.1136/annrheumdis-2017-212628
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: At 2 weeks, patients who had received the intramuscular glucocorticoid injection had a significant and clinically relevant difference in hip pain at rest (between-group difference = –1.3; 95% CI, –2.3 to –0.3; P = .01).
Study details: A 12-week, double blinded, placebo-controlled trial of 106 patients with hip OA randomized to 40 mg triamcinolone acetate or placebo injection.
Disclosures: Financial support for the study came from the Dutch Arthritis Foundation and the NutsOhra fund. Two of the authors reported receiving grants from several pharmaceutical companies, research consortia, and foundations.
Source: Dorleijn D et al. Ann Rheum Dis. 2018 Mar 7. doi: 10.1136/annrheumdis-2017-212628.
Nonopioid analgesics have no major disadvantages vs. opioids for chronic pain
Patients treated with opioids for moderate to severe chronic back pain or knee or hip osteoarthritis pain saw no significant improvement when results were compared with treatment using acetaminophen or nonsteroidal anti-inflammatory drugs in the randomized SPACE study.
These findings may help restructure how physicians treat patients with chronic pain in order to decrease the risk of opioid addiction in a population that is particularly susceptible.
“Long-term opioid therapy became a standard approach to managing chronic musculoskeletal pain despite a lack of high-quality data on benefits and harms,” wrote Erin E. Krebs, MD, MPH, core investigator at the Minneapolis Veterans Affairs Center for Chronic Disease Outcomes Research, and her colleagues. “Rising rates of opioid overdose deaths have raised questions about prescribing opioids for chronic pain management.”
In the 12-month SPACE (Strategies for Prescribing Analgesics Comparative Effectiveness) trial published March 6 in JAMA, the investigators reported randomizing a total of 240 patients to treatment with immediate-release opioids (morphine, oxycodone, or hydrocodone/acetaminophen) or acetaminophen or nonsteroidal anti-inflammatory drugs. The patients came from the Minneapolis VA system between June 2013 and December 2015. Patients in the opioid group were on average 57 years old, while those in the nonopioid group had an average age of 60 years. Men comprised 87% of all patients, and both groups were predominantly white (86%-88%) with chronic back pain (65%). The investigators excluded patients with physiological opioid dependence from ongoing opioid use.
Patients taking opioids saw no significant improvement in the primary outcome of pain-related function on the seven-item Brief Pain Inventory (BPI) interference scale over those taking nonopioids at the end of the 12-month period (P = .58), according to Dr. Krebs and her fellow investigators.
The main secondary outcome of pain intensity using the four-item BPI severity scale improved significantly more among the nonopioid group, which reported an average score of 3.5, compared with 4.0 in the opioid group (P = .03). However, the small difference of 0.5 is less than the minimal clinically important difference of 1.0, according to the investigators.
Anxiety control was the only secondary outcome measure that was significantly better among patients in the opioid group, which was unsurprising to the investigators. “This finding is consistent with the role of the endogenous opioid system in stress and emotional suffering,” they wrote.
The investigators were uncertain about the significance of this small difference because overall anxiety levels were low, with 9% of patients reporting moderate severity anxiety symptoms at baseline.
Patients in the opioid group took a mean of 1.7 analgesics during the study period, compared with 3.8 in the nonopioid group. In the nonopioid group, the mean number of months that nonopioid analgesics were prescribed ranged from 2.6 for acetaminophen to 5.9 with oral NSAIDs. In this group, tramadol was prescribed to no more than 11% of patients during any particular month and was dispensed for a mean of 0.4 months overall.
Patients in the opioid group took opioids for a mean of 8.1 months, with all other analgesics taken for a mean of 0.4 months or less. The authors noted that in “each 90-day follow-up period, fewer than 15% of patients in the opioid group had a mean dispensed dosage of 50 morphine-equivalent mg/day or more.” Patients could be titrated up to a maximum daily dosage of 100 morphine-equivalent mg/day.
Patients prescribed opioids were significantly more likely to report medication-related symptoms, and while misuse was not significantly higher in the opioid group, the investigators said that “Overall, opioids did not demonstrate any advantage over nonopioid medications that could potentially outweigh their greater risk of harms.”
Further studies will need to include a more diverse population, they noted.
The study was funded by an award from the U.S. Department of Veterans Affairs Health Services Research and Development Service. The investigators reported no relevant disclosures.
SOURCE: Krebs EE et al. JAMA. 2018 Mar 6;319(9):872-82
Patients treated with opioids for moderate to severe chronic back pain or knee or hip osteoarthritis pain saw no significant improvement when results were compared with treatment using acetaminophen or nonsteroidal anti-inflammatory drugs in the randomized SPACE study.
These findings may help restructure how physicians treat patients with chronic pain in order to decrease the risk of opioid addiction in a population that is particularly susceptible.
“Long-term opioid therapy became a standard approach to managing chronic musculoskeletal pain despite a lack of high-quality data on benefits and harms,” wrote Erin E. Krebs, MD, MPH, core investigator at the Minneapolis Veterans Affairs Center for Chronic Disease Outcomes Research, and her colleagues. “Rising rates of opioid overdose deaths have raised questions about prescribing opioids for chronic pain management.”
In the 12-month SPACE (Strategies for Prescribing Analgesics Comparative Effectiveness) trial published March 6 in JAMA, the investigators reported randomizing a total of 240 patients to treatment with immediate-release opioids (morphine, oxycodone, or hydrocodone/acetaminophen) or acetaminophen or nonsteroidal anti-inflammatory drugs. The patients came from the Minneapolis VA system between June 2013 and December 2015. Patients in the opioid group were on average 57 years old, while those in the nonopioid group had an average age of 60 years. Men comprised 87% of all patients, and both groups were predominantly white (86%-88%) with chronic back pain (65%). The investigators excluded patients with physiological opioid dependence from ongoing opioid use.
Patients taking opioids saw no significant improvement in the primary outcome of pain-related function on the seven-item Brief Pain Inventory (BPI) interference scale over those taking nonopioids at the end of the 12-month period (P = .58), according to Dr. Krebs and her fellow investigators.
The main secondary outcome of pain intensity using the four-item BPI severity scale improved significantly more among the nonopioid group, which reported an average score of 3.5, compared with 4.0 in the opioid group (P = .03). However, the small difference of 0.5 is less than the minimal clinically important difference of 1.0, according to the investigators.
Anxiety control was the only secondary outcome measure that was significantly better among patients in the opioid group, which was unsurprising to the investigators. “This finding is consistent with the role of the endogenous opioid system in stress and emotional suffering,” they wrote.
The investigators were uncertain about the significance of this small difference because overall anxiety levels were low, with 9% of patients reporting moderate severity anxiety symptoms at baseline.
Patients in the opioid group took a mean of 1.7 analgesics during the study period, compared with 3.8 in the nonopioid group. In the nonopioid group, the mean number of months that nonopioid analgesics were prescribed ranged from 2.6 for acetaminophen to 5.9 with oral NSAIDs. In this group, tramadol was prescribed to no more than 11% of patients during any particular month and was dispensed for a mean of 0.4 months overall.
Patients in the opioid group took opioids for a mean of 8.1 months, with all other analgesics taken for a mean of 0.4 months or less. The authors noted that in “each 90-day follow-up period, fewer than 15% of patients in the opioid group had a mean dispensed dosage of 50 morphine-equivalent mg/day or more.” Patients could be titrated up to a maximum daily dosage of 100 morphine-equivalent mg/day.
Patients prescribed opioids were significantly more likely to report medication-related symptoms, and while misuse was not significantly higher in the opioid group, the investigators said that “Overall, opioids did not demonstrate any advantage over nonopioid medications that could potentially outweigh their greater risk of harms.”
Further studies will need to include a more diverse population, they noted.
The study was funded by an award from the U.S. Department of Veterans Affairs Health Services Research and Development Service. The investigators reported no relevant disclosures.
SOURCE: Krebs EE et al. JAMA. 2018 Mar 6;319(9):872-82
Patients treated with opioids for moderate to severe chronic back pain or knee or hip osteoarthritis pain saw no significant improvement when results were compared with treatment using acetaminophen or nonsteroidal anti-inflammatory drugs in the randomized SPACE study.
These findings may help restructure how physicians treat patients with chronic pain in order to decrease the risk of opioid addiction in a population that is particularly susceptible.
“Long-term opioid therapy became a standard approach to managing chronic musculoskeletal pain despite a lack of high-quality data on benefits and harms,” wrote Erin E. Krebs, MD, MPH, core investigator at the Minneapolis Veterans Affairs Center for Chronic Disease Outcomes Research, and her colleagues. “Rising rates of opioid overdose deaths have raised questions about prescribing opioids for chronic pain management.”
In the 12-month SPACE (Strategies for Prescribing Analgesics Comparative Effectiveness) trial published March 6 in JAMA, the investigators reported randomizing a total of 240 patients to treatment with immediate-release opioids (morphine, oxycodone, or hydrocodone/acetaminophen) or acetaminophen or nonsteroidal anti-inflammatory drugs. The patients came from the Minneapolis VA system between June 2013 and December 2015. Patients in the opioid group were on average 57 years old, while those in the nonopioid group had an average age of 60 years. Men comprised 87% of all patients, and both groups were predominantly white (86%-88%) with chronic back pain (65%). The investigators excluded patients with physiological opioid dependence from ongoing opioid use.
Patients taking opioids saw no significant improvement in the primary outcome of pain-related function on the seven-item Brief Pain Inventory (BPI) interference scale over those taking nonopioids at the end of the 12-month period (P = .58), according to Dr. Krebs and her fellow investigators.
The main secondary outcome of pain intensity using the four-item BPI severity scale improved significantly more among the nonopioid group, which reported an average score of 3.5, compared with 4.0 in the opioid group (P = .03). However, the small difference of 0.5 is less than the minimal clinically important difference of 1.0, according to the investigators.
Anxiety control was the only secondary outcome measure that was significantly better among patients in the opioid group, which was unsurprising to the investigators. “This finding is consistent with the role of the endogenous opioid system in stress and emotional suffering,” they wrote.
The investigators were uncertain about the significance of this small difference because overall anxiety levels were low, with 9% of patients reporting moderate severity anxiety symptoms at baseline.
Patients in the opioid group took a mean of 1.7 analgesics during the study period, compared with 3.8 in the nonopioid group. In the nonopioid group, the mean number of months that nonopioid analgesics were prescribed ranged from 2.6 for acetaminophen to 5.9 with oral NSAIDs. In this group, tramadol was prescribed to no more than 11% of patients during any particular month and was dispensed for a mean of 0.4 months overall.
Patients in the opioid group took opioids for a mean of 8.1 months, with all other analgesics taken for a mean of 0.4 months or less. The authors noted that in “each 90-day follow-up period, fewer than 15% of patients in the opioid group had a mean dispensed dosage of 50 morphine-equivalent mg/day or more.” Patients could be titrated up to a maximum daily dosage of 100 morphine-equivalent mg/day.
Patients prescribed opioids were significantly more likely to report medication-related symptoms, and while misuse was not significantly higher in the opioid group, the investigators said that “Overall, opioids did not demonstrate any advantage over nonopioid medications that could potentially outweigh their greater risk of harms.”
Further studies will need to include a more diverse population, they noted.
The study was funded by an award from the U.S. Department of Veterans Affairs Health Services Research and Development Service. The investigators reported no relevant disclosures.
SOURCE: Krebs EE et al. JAMA. 2018 Mar 6;319(9):872-82
FROM JAMA
Key clinical point: Opioids and nonopioid analgesics provided similar improvements in pain-related function for patients with chronic pain.
Major finding: Patients taking opioids did not show significant improvement in pain-related function, compared with those taking nonopioids (P = .58).
Study details: A 12-month, randomized trial of 240 patients with chronic back, knee, or hip pain, gathered from a Veterans Affairs clinic between June 2013 to December 2015.
Disclosures: The study was funded by an award from the U.S. Department of Veterans Affairs Health Services Research and Development Service. The investigators reported no relevant disclosures.
Source: Krebs E et al. JAMA. 2018;319(9):872-82
Experts review the year in rheumatology ... and what lies ahead
MAUI, HAWAII – Arthur Kavanaugh, MD, program director for the Rheumatology Winter Clinical Symposium, likes to close out the meeting each year in high style by assembling selected conference faculty to offer their personal picks for the top developments in the field during the past year and make predictions about the year to come.
Here’s how they called it:
The top events in rheumatology during the last year
The rise of oral small molecules: The Janus kinase (JAK) inhibitors and other oral small molecules that have begun reaching the marketplace, with many more in development, will bring a paradigm shift in the treatment not only of rheumatic diseases, but in inflammatory bowel disease and skin diseases as well, predicted Alvin F. Wells, MD, PhD, a rheumatologist at Duke University in Durham, N.C., who is also director of the Rheumatology and Immunotherapy Center in Franklin, Wisc.
“The challenge is whether Medicare will cover the pills the way they cover the infusions and the other things we do,” according to Dr. Wells.
A bevy of new drugs for psoriatic arthritis and psoriasis: “I think the most important advance in the past year was the approval of a profusion of drugs for psoriatic arthritis and psoriasis. It’s really opened up the landscape for us in terms of treatment options. The downside is it’s going to take us a while to sort through which drugs fit where,” noted Eric J. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University in Chicago.
“The drug I was most impressed with was tofacitinib [Xeljanz, an oral JAK inhibitor], not just by its effectiveness but by its potential to change the game, and particularly the data in tumor necrosis factor inhibitor inadequate responders. That was pretty solid data. It really opens the way to oral small molecules for joint diseases,” he added.
Interleukin-18 binding protein for monogenic inflammasome diseases: The biggest recent breakthrough in pediatric rheumatology was the Food and Drug Administration’s April 2017 designation of Breakthrough Therapy status for the recombinant human IL-18 binding protein known as tadekinig alfa for monogenic IL-18-associated autoinflammatory conditions, as well as the biologic’s Orphan Drug Designation for treatment of hemophagocytic lymphohistiocytosis, according to Anne M. Stevens, MD, PhD, professor of pediatrics at the University of Washington, Seattle, and chief of pediatric rheumatology at Seattle Children’s Hospital.
Novel treatment concept emerges in severe SLE: The study that knocked the socks off of Martin J. Bergman, MD, in 2017 was the Dutch SymBiose study, presented at both the European League Against Rheumatism and American College of Rheumatology annual meetings. It included just 14 patients with severe refractory SLE – including 10 with lupus nephritis – and tested a treatment strategy of rituximab (Rituxan) followed a few weeks later by a course of belimumab (Benlysta).
“The results were very dramatic, to say the least,” said Dr. Bergman of Drexel University in Philadelphia. Indeed, this one-two therapeutic punch resulted in sharply reduced levels of pathogenic autoantibodies and immune complex-mediated neutrophil extracellular traps while also knocking down very high baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores to near zero, even while enabling patients to discontinue systemic corticosteroids and mycophenolate mofetil (CellCept). Several much larger clinical trials of this regimen and other similar ones are ongoing in an effort to duplicate the results.
Dr. Kavanaugh said the SymBiose study was one of his own top picks for study of the year as well.
Mainstream use of dupilumab (Dupixent) for moderate to severe atopic dermatitis: “This is a total game changer. It’s really changed a lot of people’s lives,” commented George M. Martin, MD, a dermatologist in private practice on Maui.
“Interestingly, historically drugs that started out in your realm later made their way to dermatology, but now we’re seeing the IL-23 inhibitors starting with us and then making their way into rheumatology and gastroenterology. The IL-23 inhibitors are very powerful drugs; when we’re seeing half of our psoriasis patients achieve PASI 100 responses, it’s very exciting. And these are durable responses,” he noted.
The opioid crisis: What’s the most important recent event in rheumatology?
“That’s easy: The biggest thing in all of medicine is the opioid crisis. Whether you recognize it or not, it’s gigantic. It’s $500 billion of the U.S. economy, every year. Forty percent of rheumatoid arthritis patients and 30% with ankylosing spondylitis are on opioids, and what goes along with that is a lot of ugly stuff,” said John J. Cush, MD, professor of medicine and rheumatology at Baylor University in Dallas.
Moreover, the FDA is now so leery of opioids that the agency has set the bar unrealistically high for approval of newer agents offering reduced abuse potential.
“I’ve been involved with or watched at least six FDA advisory panels looking at new, lower abuse-potential opioids in the last couple years. Only one agent got through,” according to Dr. Cush.
Dr. Troum commented, “I really think this whole opioid epidemic started with the campaign to make pain the fifth vital sign back in the 1990s. Some of the pharmaceutical companies took that concept and really ran with it.”
Rapamycin for inclusion body myositis: Dr. Kavanaugh’s pick for study of the year was what he described as “a brilliant presentation” of a French multicenter, placebo-controlled clinical trial of rapamycin for patients with inclusion body myositis at the 2017 ACR annual meeting.
“The French group considers IBM [inclusion body myositis] to be essentially Alzheimer’s disease of the muscle, marked by amyloid deposition. They chose to study rapamycin, which not only has immunosuppressive properties because it binds to mTOR [the mammalian target of rapamycin], but it also has the ability to inhibit amyloid protein deposition,” he explained.
The investigators reported improved 6-minute-walk distance and pulmonary function in the rapamycin group, whereas placebo-treated controls rapidly deteriorated.
“This is an approved drug for other indications, and we scratch our heads with IBM. It’s super nice to have something like that,” Dr. Kavanaugh observed.
A look at what’s in store
More tele-rheumatology: “I think the biggest thing is going to be more tele-rheumatology, more tele-ultrasound. Kaiser Permanente said 49% of their visits last year were virtual visits; that number is just going to grow,” predicted Dr. Wells.
Especially in medically underserved areas of the country, including large rural expanses, demand for remote tele-rheumatologic consults with high-quality imaging is going to increase, he added.
Here come cannabinoids for pain control: Dr. Troum predicted that in the depths of the national opioid epidemic, in a climate that discourages legitimate prescribing of traditional pain medications, rheumatologists can anticipate growing patient demand for cannabidiol and other cannabinoids for pain relief.
“I have patients coming in their 60s, 70s, and 80s – these are not young people – who are whispering to me, ‘Can I use this for my chronic pain?’ I think there’s going to be a big push for ways other than opioids to treat our patients’ pain,” according to Dr. Troum.
Tipping point nears for JAK inhibitors: In 2018, it will become clear just how seriously the Food and Drug Administration views the signal of possible increased venous thromboembolic risk associated with the oral JAK inhibitors for rheumatoid arthritis. The agency is expected to rule on Eli Lilly and Incyte’s resubmitted application for marketing approval for the JAK inhibitor baricitinib, which was tripped up earlier based in part upon VTE concerns.
“I think the big story in 2018 will be how the JAK story shakes out – whether this VTE thing has legs,” Dr. Ruderman predicted. “A sea change could be coming in our field, and it’s not coming next year or the year after, but 10 years from now: Are we going to move past the era of methotrexate and use generic small molecules instead? We’re going to find out within the next year whether that’s going to happen.”
Phase 3 results coming on tocilizumab for systemic sclerosis: “I think we’re going to see some really exciting systemic sclerosis data coming out this year,” Dr. Stevens said. Based upon the positive phase 2 results presented for tocilizumab (Actemra) last year, she’s optimistic that the ongoing phase 3 randomized trial will demonstrate a significant advantage over placebo in lung function. Also, ongoing separate clinical trials are evaluating an antifibrotic drug and rapamycin for systemic sclerosis.
Dr. Bergman, too, has high hopes for these studies: “I think we may finally be getting to a place where we can see effective drugs in systemic sclerosis.”
Amazon, Berkshire Hathaway, and JPMorgan Chase form a nonprofit to improve employee health care: In a recent press conference, the three CEOs weren’t specific about their plans, but Dr. Martin predicted the companies are likely to self-insure, bypassing Cigna and the other major health insurance companies and then contracting with physicians. He forecast that “probably within the next 5 years, what they do is going to affect everybody in this room.”
Rheumatologists will need to master a new mindset: Many rheumatologists have gotten comfortable with an all-tumor necrosis factor inhibitor treatment menu for their patients with moderate or severe rheumatoid arthritis. That’s got to change, according to Dr. Cush.
“We now have two IL-6 inhibitors, two IL-17 inhibitors, and we’ll soon have two JAK inhibitors. That’s going to be a direct threat to the not right- or left-brain, but the TNF-brain rheumatologist who now writes prescriptions for three TNF inhibitors in a row before questioning the efficacy. The idea is you will now be using drugs with other mechanisms of action first-line, or at the very least, second-line, and that’s going to be a paradigm shift for a lot of people,” he explained.
None of the speakers reported having financial conflicts regarding their comments.
MAUI, HAWAII – Arthur Kavanaugh, MD, program director for the Rheumatology Winter Clinical Symposium, likes to close out the meeting each year in high style by assembling selected conference faculty to offer their personal picks for the top developments in the field during the past year and make predictions about the year to come.
Here’s how they called it:
The top events in rheumatology during the last year
The rise of oral small molecules: The Janus kinase (JAK) inhibitors and other oral small molecules that have begun reaching the marketplace, with many more in development, will bring a paradigm shift in the treatment not only of rheumatic diseases, but in inflammatory bowel disease and skin diseases as well, predicted Alvin F. Wells, MD, PhD, a rheumatologist at Duke University in Durham, N.C., who is also director of the Rheumatology and Immunotherapy Center in Franklin, Wisc.
“The challenge is whether Medicare will cover the pills the way they cover the infusions and the other things we do,” according to Dr. Wells.
A bevy of new drugs for psoriatic arthritis and psoriasis: “I think the most important advance in the past year was the approval of a profusion of drugs for psoriatic arthritis and psoriasis. It’s really opened up the landscape for us in terms of treatment options. The downside is it’s going to take us a while to sort through which drugs fit where,” noted Eric J. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University in Chicago.
“The drug I was most impressed with was tofacitinib [Xeljanz, an oral JAK inhibitor], not just by its effectiveness but by its potential to change the game, and particularly the data in tumor necrosis factor inhibitor inadequate responders. That was pretty solid data. It really opens the way to oral small molecules for joint diseases,” he added.
Interleukin-18 binding protein for monogenic inflammasome diseases: The biggest recent breakthrough in pediatric rheumatology was the Food and Drug Administration’s April 2017 designation of Breakthrough Therapy status for the recombinant human IL-18 binding protein known as tadekinig alfa for monogenic IL-18-associated autoinflammatory conditions, as well as the biologic’s Orphan Drug Designation for treatment of hemophagocytic lymphohistiocytosis, according to Anne M. Stevens, MD, PhD, professor of pediatrics at the University of Washington, Seattle, and chief of pediatric rheumatology at Seattle Children’s Hospital.
Novel treatment concept emerges in severe SLE: The study that knocked the socks off of Martin J. Bergman, MD, in 2017 was the Dutch SymBiose study, presented at both the European League Against Rheumatism and American College of Rheumatology annual meetings. It included just 14 patients with severe refractory SLE – including 10 with lupus nephritis – and tested a treatment strategy of rituximab (Rituxan) followed a few weeks later by a course of belimumab (Benlysta).
“The results were very dramatic, to say the least,” said Dr. Bergman of Drexel University in Philadelphia. Indeed, this one-two therapeutic punch resulted in sharply reduced levels of pathogenic autoantibodies and immune complex-mediated neutrophil extracellular traps while also knocking down very high baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores to near zero, even while enabling patients to discontinue systemic corticosteroids and mycophenolate mofetil (CellCept). Several much larger clinical trials of this regimen and other similar ones are ongoing in an effort to duplicate the results.
Dr. Kavanaugh said the SymBiose study was one of his own top picks for study of the year as well.
Mainstream use of dupilumab (Dupixent) for moderate to severe atopic dermatitis: “This is a total game changer. It’s really changed a lot of people’s lives,” commented George M. Martin, MD, a dermatologist in private practice on Maui.
“Interestingly, historically drugs that started out in your realm later made their way to dermatology, but now we’re seeing the IL-23 inhibitors starting with us and then making their way into rheumatology and gastroenterology. The IL-23 inhibitors are very powerful drugs; when we’re seeing half of our psoriasis patients achieve PASI 100 responses, it’s very exciting. And these are durable responses,” he noted.
The opioid crisis: What’s the most important recent event in rheumatology?
“That’s easy: The biggest thing in all of medicine is the opioid crisis. Whether you recognize it or not, it’s gigantic. It’s $500 billion of the U.S. economy, every year. Forty percent of rheumatoid arthritis patients and 30% with ankylosing spondylitis are on opioids, and what goes along with that is a lot of ugly stuff,” said John J. Cush, MD, professor of medicine and rheumatology at Baylor University in Dallas.
Moreover, the FDA is now so leery of opioids that the agency has set the bar unrealistically high for approval of newer agents offering reduced abuse potential.
“I’ve been involved with or watched at least six FDA advisory panels looking at new, lower abuse-potential opioids in the last couple years. Only one agent got through,” according to Dr. Cush.
Dr. Troum commented, “I really think this whole opioid epidemic started with the campaign to make pain the fifth vital sign back in the 1990s. Some of the pharmaceutical companies took that concept and really ran with it.”
Rapamycin for inclusion body myositis: Dr. Kavanaugh’s pick for study of the year was what he described as “a brilliant presentation” of a French multicenter, placebo-controlled clinical trial of rapamycin for patients with inclusion body myositis at the 2017 ACR annual meeting.
“The French group considers IBM [inclusion body myositis] to be essentially Alzheimer’s disease of the muscle, marked by amyloid deposition. They chose to study rapamycin, which not only has immunosuppressive properties because it binds to mTOR [the mammalian target of rapamycin], but it also has the ability to inhibit amyloid protein deposition,” he explained.
The investigators reported improved 6-minute-walk distance and pulmonary function in the rapamycin group, whereas placebo-treated controls rapidly deteriorated.
“This is an approved drug for other indications, and we scratch our heads with IBM. It’s super nice to have something like that,” Dr. Kavanaugh observed.
A look at what’s in store
More tele-rheumatology: “I think the biggest thing is going to be more tele-rheumatology, more tele-ultrasound. Kaiser Permanente said 49% of their visits last year were virtual visits; that number is just going to grow,” predicted Dr. Wells.
Especially in medically underserved areas of the country, including large rural expanses, demand for remote tele-rheumatologic consults with high-quality imaging is going to increase, he added.
Here come cannabinoids for pain control: Dr. Troum predicted that in the depths of the national opioid epidemic, in a climate that discourages legitimate prescribing of traditional pain medications, rheumatologists can anticipate growing patient demand for cannabidiol and other cannabinoids for pain relief.
“I have patients coming in their 60s, 70s, and 80s – these are not young people – who are whispering to me, ‘Can I use this for my chronic pain?’ I think there’s going to be a big push for ways other than opioids to treat our patients’ pain,” according to Dr. Troum.
Tipping point nears for JAK inhibitors: In 2018, it will become clear just how seriously the Food and Drug Administration views the signal of possible increased venous thromboembolic risk associated with the oral JAK inhibitors for rheumatoid arthritis. The agency is expected to rule on Eli Lilly and Incyte’s resubmitted application for marketing approval for the JAK inhibitor baricitinib, which was tripped up earlier based in part upon VTE concerns.
“I think the big story in 2018 will be how the JAK story shakes out – whether this VTE thing has legs,” Dr. Ruderman predicted. “A sea change could be coming in our field, and it’s not coming next year or the year after, but 10 years from now: Are we going to move past the era of methotrexate and use generic small molecules instead? We’re going to find out within the next year whether that’s going to happen.”
Phase 3 results coming on tocilizumab for systemic sclerosis: “I think we’re going to see some really exciting systemic sclerosis data coming out this year,” Dr. Stevens said. Based upon the positive phase 2 results presented for tocilizumab (Actemra) last year, she’s optimistic that the ongoing phase 3 randomized trial will demonstrate a significant advantage over placebo in lung function. Also, ongoing separate clinical trials are evaluating an antifibrotic drug and rapamycin for systemic sclerosis.
Dr. Bergman, too, has high hopes for these studies: “I think we may finally be getting to a place where we can see effective drugs in systemic sclerosis.”
Amazon, Berkshire Hathaway, and JPMorgan Chase form a nonprofit to improve employee health care: In a recent press conference, the three CEOs weren’t specific about their plans, but Dr. Martin predicted the companies are likely to self-insure, bypassing Cigna and the other major health insurance companies and then contracting with physicians. He forecast that “probably within the next 5 years, what they do is going to affect everybody in this room.”
Rheumatologists will need to master a new mindset: Many rheumatologists have gotten comfortable with an all-tumor necrosis factor inhibitor treatment menu for their patients with moderate or severe rheumatoid arthritis. That’s got to change, according to Dr. Cush.
“We now have two IL-6 inhibitors, two IL-17 inhibitors, and we’ll soon have two JAK inhibitors. That’s going to be a direct threat to the not right- or left-brain, but the TNF-brain rheumatologist who now writes prescriptions for three TNF inhibitors in a row before questioning the efficacy. The idea is you will now be using drugs with other mechanisms of action first-line, or at the very least, second-line, and that’s going to be a paradigm shift for a lot of people,” he explained.
None of the speakers reported having financial conflicts regarding their comments.
MAUI, HAWAII – Arthur Kavanaugh, MD, program director for the Rheumatology Winter Clinical Symposium, likes to close out the meeting each year in high style by assembling selected conference faculty to offer their personal picks for the top developments in the field during the past year and make predictions about the year to come.
Here’s how they called it:
The top events in rheumatology during the last year
The rise of oral small molecules: The Janus kinase (JAK) inhibitors and other oral small molecules that have begun reaching the marketplace, with many more in development, will bring a paradigm shift in the treatment not only of rheumatic diseases, but in inflammatory bowel disease and skin diseases as well, predicted Alvin F. Wells, MD, PhD, a rheumatologist at Duke University in Durham, N.C., who is also director of the Rheumatology and Immunotherapy Center in Franklin, Wisc.
“The challenge is whether Medicare will cover the pills the way they cover the infusions and the other things we do,” according to Dr. Wells.
A bevy of new drugs for psoriatic arthritis and psoriasis: “I think the most important advance in the past year was the approval of a profusion of drugs for psoriatic arthritis and psoriasis. It’s really opened up the landscape for us in terms of treatment options. The downside is it’s going to take us a while to sort through which drugs fit where,” noted Eric J. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University in Chicago.
“The drug I was most impressed with was tofacitinib [Xeljanz, an oral JAK inhibitor], not just by its effectiveness but by its potential to change the game, and particularly the data in tumor necrosis factor inhibitor inadequate responders. That was pretty solid data. It really opens the way to oral small molecules for joint diseases,” he added.
Interleukin-18 binding protein for monogenic inflammasome diseases: The biggest recent breakthrough in pediatric rheumatology was the Food and Drug Administration’s April 2017 designation of Breakthrough Therapy status for the recombinant human IL-18 binding protein known as tadekinig alfa for monogenic IL-18-associated autoinflammatory conditions, as well as the biologic’s Orphan Drug Designation for treatment of hemophagocytic lymphohistiocytosis, according to Anne M. Stevens, MD, PhD, professor of pediatrics at the University of Washington, Seattle, and chief of pediatric rheumatology at Seattle Children’s Hospital.
Novel treatment concept emerges in severe SLE: The study that knocked the socks off of Martin J. Bergman, MD, in 2017 was the Dutch SymBiose study, presented at both the European League Against Rheumatism and American College of Rheumatology annual meetings. It included just 14 patients with severe refractory SLE – including 10 with lupus nephritis – and tested a treatment strategy of rituximab (Rituxan) followed a few weeks later by a course of belimumab (Benlysta).
“The results were very dramatic, to say the least,” said Dr. Bergman of Drexel University in Philadelphia. Indeed, this one-two therapeutic punch resulted in sharply reduced levels of pathogenic autoantibodies and immune complex-mediated neutrophil extracellular traps while also knocking down very high baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores to near zero, even while enabling patients to discontinue systemic corticosteroids and mycophenolate mofetil (CellCept). Several much larger clinical trials of this regimen and other similar ones are ongoing in an effort to duplicate the results.
Dr. Kavanaugh said the SymBiose study was one of his own top picks for study of the year as well.
Mainstream use of dupilumab (Dupixent) for moderate to severe atopic dermatitis: “This is a total game changer. It’s really changed a lot of people’s lives,” commented George M. Martin, MD, a dermatologist in private practice on Maui.
“Interestingly, historically drugs that started out in your realm later made their way to dermatology, but now we’re seeing the IL-23 inhibitors starting with us and then making their way into rheumatology and gastroenterology. The IL-23 inhibitors are very powerful drugs; when we’re seeing half of our psoriasis patients achieve PASI 100 responses, it’s very exciting. And these are durable responses,” he noted.
The opioid crisis: What’s the most important recent event in rheumatology?
“That’s easy: The biggest thing in all of medicine is the opioid crisis. Whether you recognize it or not, it’s gigantic. It’s $500 billion of the U.S. economy, every year. Forty percent of rheumatoid arthritis patients and 30% with ankylosing spondylitis are on opioids, and what goes along with that is a lot of ugly stuff,” said John J. Cush, MD, professor of medicine and rheumatology at Baylor University in Dallas.
Moreover, the FDA is now so leery of opioids that the agency has set the bar unrealistically high for approval of newer agents offering reduced abuse potential.
“I’ve been involved with or watched at least six FDA advisory panels looking at new, lower abuse-potential opioids in the last couple years. Only one agent got through,” according to Dr. Cush.
Dr. Troum commented, “I really think this whole opioid epidemic started with the campaign to make pain the fifth vital sign back in the 1990s. Some of the pharmaceutical companies took that concept and really ran with it.”
Rapamycin for inclusion body myositis: Dr. Kavanaugh’s pick for study of the year was what he described as “a brilliant presentation” of a French multicenter, placebo-controlled clinical trial of rapamycin for patients with inclusion body myositis at the 2017 ACR annual meeting.
“The French group considers IBM [inclusion body myositis] to be essentially Alzheimer’s disease of the muscle, marked by amyloid deposition. They chose to study rapamycin, which not only has immunosuppressive properties because it binds to mTOR [the mammalian target of rapamycin], but it also has the ability to inhibit amyloid protein deposition,” he explained.
The investigators reported improved 6-minute-walk distance and pulmonary function in the rapamycin group, whereas placebo-treated controls rapidly deteriorated.
“This is an approved drug for other indications, and we scratch our heads with IBM. It’s super nice to have something like that,” Dr. Kavanaugh observed.
A look at what’s in store
More tele-rheumatology: “I think the biggest thing is going to be more tele-rheumatology, more tele-ultrasound. Kaiser Permanente said 49% of their visits last year were virtual visits; that number is just going to grow,” predicted Dr. Wells.
Especially in medically underserved areas of the country, including large rural expanses, demand for remote tele-rheumatologic consults with high-quality imaging is going to increase, he added.
Here come cannabinoids for pain control: Dr. Troum predicted that in the depths of the national opioid epidemic, in a climate that discourages legitimate prescribing of traditional pain medications, rheumatologists can anticipate growing patient demand for cannabidiol and other cannabinoids for pain relief.
“I have patients coming in their 60s, 70s, and 80s – these are not young people – who are whispering to me, ‘Can I use this for my chronic pain?’ I think there’s going to be a big push for ways other than opioids to treat our patients’ pain,” according to Dr. Troum.
Tipping point nears for JAK inhibitors: In 2018, it will become clear just how seriously the Food and Drug Administration views the signal of possible increased venous thromboembolic risk associated with the oral JAK inhibitors for rheumatoid arthritis. The agency is expected to rule on Eli Lilly and Incyte’s resubmitted application for marketing approval for the JAK inhibitor baricitinib, which was tripped up earlier based in part upon VTE concerns.
“I think the big story in 2018 will be how the JAK story shakes out – whether this VTE thing has legs,” Dr. Ruderman predicted. “A sea change could be coming in our field, and it’s not coming next year or the year after, but 10 years from now: Are we going to move past the era of methotrexate and use generic small molecules instead? We’re going to find out within the next year whether that’s going to happen.”
Phase 3 results coming on tocilizumab for systemic sclerosis: “I think we’re going to see some really exciting systemic sclerosis data coming out this year,” Dr. Stevens said. Based upon the positive phase 2 results presented for tocilizumab (Actemra) last year, she’s optimistic that the ongoing phase 3 randomized trial will demonstrate a significant advantage over placebo in lung function. Also, ongoing separate clinical trials are evaluating an antifibrotic drug and rapamycin for systemic sclerosis.
Dr. Bergman, too, has high hopes for these studies: “I think we may finally be getting to a place where we can see effective drugs in systemic sclerosis.”
Amazon, Berkshire Hathaway, and JPMorgan Chase form a nonprofit to improve employee health care: In a recent press conference, the three CEOs weren’t specific about their plans, but Dr. Martin predicted the companies are likely to self-insure, bypassing Cigna and the other major health insurance companies and then contracting with physicians. He forecast that “probably within the next 5 years, what they do is going to affect everybody in this room.”
Rheumatologists will need to master a new mindset: Many rheumatologists have gotten comfortable with an all-tumor necrosis factor inhibitor treatment menu for their patients with moderate or severe rheumatoid arthritis. That’s got to change, according to Dr. Cush.
“We now have two IL-6 inhibitors, two IL-17 inhibitors, and we’ll soon have two JAK inhibitors. That’s going to be a direct threat to the not right- or left-brain, but the TNF-brain rheumatologist who now writes prescriptions for three TNF inhibitors in a row before questioning the efficacy. The idea is you will now be using drugs with other mechanisms of action first-line, or at the very least, second-line, and that’s going to be a paradigm shift for a lot of people,” he explained.
None of the speakers reported having financial conflicts regarding their comments.
EXPERT ANALYSIS FROM RWCS 2018
Turmeric-, frankincense-derived supplement shows OA benefit
A combination of curcumin extracted from the turmeric rhizome and boswellic acid extracted from Indian frankincense root beat placebo for reducing pain-related symptoms from knee osteoarthritis in a 12-week clinical trial from Armenia with 201 patients 40-70 years old.
The combination (Curamin) also beat a standalone curcumin preparation (CuraMed), according to a report in BMC Complementary and Alternative Medicine.
It appears that combining the two “increases the efficacy of treatment of OA presumably due to synergistic effects of curcumin and boswellic acid”; it’s also possible that boswellic acid increases curcumin bioavailability, said investigators led by Armine Haroyan, PhD, head of rheumatology at Erebuni Medical Center in Yerevan, Armenia.
The subjects were randomized evenly to the combination, curcumin alone, or placebo, all in 500-mg capsules taken three times daily. They had been diagnosed with degenerative hypertrophic OA of knee bone joints.
At the end of 12 weeks, patients on the combination outperformed those on placebo in physical performance tests and joint pain scores; curcumin outperformed placebo in only a few of the physical tests.
For instance, patients on the combination were a mean of 2.03 seconds quicker than baseline in a stair-climbing exercise by the end of the study, versus 0.22 seconds in the placebo group and 1.66 seconds in the curcumin group. Combination patients had a mean 7.38-point improvement on the Western Ontario and McMaster Universities Osteoarthritis Index, versus 2.26 points in the placebo arm and 6.34 points in the curcumin group. The differences versus placebo were statistically significant for the combination, but not for stand-alone curcumin.
The treatments were well tolerated, with only a few patients in each arm reporting nausea, gastroesophageal reflux, and similar problems.
The work was funded in part by EuroPharma USA, maker of the supplements. The authors said they had no competing interests.
SOURCE: Haroyan A et al. BMC Complement Altern Med. 2018 Jan 9;18:7. doi: 10.1186/s12906-017-2062-z
A combination of curcumin extracted from the turmeric rhizome and boswellic acid extracted from Indian frankincense root beat placebo for reducing pain-related symptoms from knee osteoarthritis in a 12-week clinical trial from Armenia with 201 patients 40-70 years old.
The combination (Curamin) also beat a standalone curcumin preparation (CuraMed), according to a report in BMC Complementary and Alternative Medicine.
It appears that combining the two “increases the efficacy of treatment of OA presumably due to synergistic effects of curcumin and boswellic acid”; it’s also possible that boswellic acid increases curcumin bioavailability, said investigators led by Armine Haroyan, PhD, head of rheumatology at Erebuni Medical Center in Yerevan, Armenia.
The subjects were randomized evenly to the combination, curcumin alone, or placebo, all in 500-mg capsules taken three times daily. They had been diagnosed with degenerative hypertrophic OA of knee bone joints.
At the end of 12 weeks, patients on the combination outperformed those on placebo in physical performance tests and joint pain scores; curcumin outperformed placebo in only a few of the physical tests.
For instance, patients on the combination were a mean of 2.03 seconds quicker than baseline in a stair-climbing exercise by the end of the study, versus 0.22 seconds in the placebo group and 1.66 seconds in the curcumin group. Combination patients had a mean 7.38-point improvement on the Western Ontario and McMaster Universities Osteoarthritis Index, versus 2.26 points in the placebo arm and 6.34 points in the curcumin group. The differences versus placebo were statistically significant for the combination, but not for stand-alone curcumin.
The treatments were well tolerated, with only a few patients in each arm reporting nausea, gastroesophageal reflux, and similar problems.
The work was funded in part by EuroPharma USA, maker of the supplements. The authors said they had no competing interests.
SOURCE: Haroyan A et al. BMC Complement Altern Med. 2018 Jan 9;18:7. doi: 10.1186/s12906-017-2062-z
A combination of curcumin extracted from the turmeric rhizome and boswellic acid extracted from Indian frankincense root beat placebo for reducing pain-related symptoms from knee osteoarthritis in a 12-week clinical trial from Armenia with 201 patients 40-70 years old.
The combination (Curamin) also beat a standalone curcumin preparation (CuraMed), according to a report in BMC Complementary and Alternative Medicine.
It appears that combining the two “increases the efficacy of treatment of OA presumably due to synergistic effects of curcumin and boswellic acid”; it’s also possible that boswellic acid increases curcumin bioavailability, said investigators led by Armine Haroyan, PhD, head of rheumatology at Erebuni Medical Center in Yerevan, Armenia.
The subjects were randomized evenly to the combination, curcumin alone, or placebo, all in 500-mg capsules taken three times daily. They had been diagnosed with degenerative hypertrophic OA of knee bone joints.
At the end of 12 weeks, patients on the combination outperformed those on placebo in physical performance tests and joint pain scores; curcumin outperformed placebo in only a few of the physical tests.
For instance, patients on the combination were a mean of 2.03 seconds quicker than baseline in a stair-climbing exercise by the end of the study, versus 0.22 seconds in the placebo group and 1.66 seconds in the curcumin group. Combination patients had a mean 7.38-point improvement on the Western Ontario and McMaster Universities Osteoarthritis Index, versus 2.26 points in the placebo arm and 6.34 points in the curcumin group. The differences versus placebo were statistically significant for the combination, but not for stand-alone curcumin.
The treatments were well tolerated, with only a few patients in each arm reporting nausea, gastroesophageal reflux, and similar problems.
The work was funded in part by EuroPharma USA, maker of the supplements. The authors said they had no competing interests.
SOURCE: Haroyan A et al. BMC Complement Altern Med. 2018 Jan 9;18:7. doi: 10.1186/s12906-017-2062-z
FROM BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
Arthritis treatment costs per person held steady from 2008 to 2014
but the rise in proportion of the arthritis patients in the U.S. population led to billions more dollars being spent on this population, reported Amit D. Raval, PhD, and Ami Vyas, PhD, of the University of Rhode Island, Kingston.
Aggregate expenditures for patients with arthritis rose from $584.8 billion in 2008 to $645 billion in 2014, accounting for about 4% of the U.S. gross domestic product in these years, the investigators reported in the Journal of Rheumatology. “The increase in aggregate unadjusted total direct health care expenditures was mainly driven through an increase in weighted population of individuals with arthritis,” which rose from 56.1 million adults with arthritis in 2008 to 65.1 million in 2014. Nonetheless, there was a “slowdown in the intensity of adjusted incremental expenditures and [out of pocket expenditures] specifically from 2013, which led to a huge decline in the aggregate direct healthcare expenditures in 2014.”
During this time period, there was an increase in the percentage of Hispanics, poor, obese, and individuals with activity limitations and mental health disorders among both those with and without arthritis. This is consistent with the study findings that incremental health care expenditures in persons with arthritis were largely driven by difference in age, health status, and chronic conditions, such as hypertension, hyperlipidemia, and heart disease, among those with and without arthritis, Dr. Raval and Dr. Vyas said.
Annual total health care expenditures in persons with arthritis fell from $10,424 in 2008 to $9,910 in 2014. The average annual total out-of-pocket expenditures in 2008 was $1,493, which was 14% of total health care expenditures that year; in 2014, this fell to $1,099. There were similar trends in persons without arthritis, Dr. Raval and Dr. Vyas reported.
The top three expenditure categories in 2008 were outpatient (32.6%), inpatient (29.0%), and prescription drug costs (24.7%); in 2014, these changed to outpatient (33.8%), prescription drug (26.8%), and inpatient costs (26.4%). There are a number of ways to explain these trends, the researchers said. It is likely that outpatient services, such as outpatient orthopedic surgeries, are becoming “a common management option for arthritis.” Also, outpatient medication services now may include administration of injectables such as biologics. There also were “relatively stable” inpatient expenditures from 2008 to 2013 and a decline in 2014. “Our findings are consistent with studies assessing the effect of the Affordable Care Act, such as introduction of the Hospital Readmission Reduction Program,” said Dr. Raval and Dr. Vyas.
SOURCE: Amit R et al. J Rheumatol. 2018 Jan 15. doi: 10.3899/jrheum.170368.
but the rise in proportion of the arthritis patients in the U.S. population led to billions more dollars being spent on this population, reported Amit D. Raval, PhD, and Ami Vyas, PhD, of the University of Rhode Island, Kingston.
Aggregate expenditures for patients with arthritis rose from $584.8 billion in 2008 to $645 billion in 2014, accounting for about 4% of the U.S. gross domestic product in these years, the investigators reported in the Journal of Rheumatology. “The increase in aggregate unadjusted total direct health care expenditures was mainly driven through an increase in weighted population of individuals with arthritis,” which rose from 56.1 million adults with arthritis in 2008 to 65.1 million in 2014. Nonetheless, there was a “slowdown in the intensity of adjusted incremental expenditures and [out of pocket expenditures] specifically from 2013, which led to a huge decline in the aggregate direct healthcare expenditures in 2014.”
During this time period, there was an increase in the percentage of Hispanics, poor, obese, and individuals with activity limitations and mental health disorders among both those with and without arthritis. This is consistent with the study findings that incremental health care expenditures in persons with arthritis were largely driven by difference in age, health status, and chronic conditions, such as hypertension, hyperlipidemia, and heart disease, among those with and without arthritis, Dr. Raval and Dr. Vyas said.
Annual total health care expenditures in persons with arthritis fell from $10,424 in 2008 to $9,910 in 2014. The average annual total out-of-pocket expenditures in 2008 was $1,493, which was 14% of total health care expenditures that year; in 2014, this fell to $1,099. There were similar trends in persons without arthritis, Dr. Raval and Dr. Vyas reported.
The top three expenditure categories in 2008 were outpatient (32.6%), inpatient (29.0%), and prescription drug costs (24.7%); in 2014, these changed to outpatient (33.8%), prescription drug (26.8%), and inpatient costs (26.4%). There are a number of ways to explain these trends, the researchers said. It is likely that outpatient services, such as outpatient orthopedic surgeries, are becoming “a common management option for arthritis.” Also, outpatient medication services now may include administration of injectables such as biologics. There also were “relatively stable” inpatient expenditures from 2008 to 2013 and a decline in 2014. “Our findings are consistent with studies assessing the effect of the Affordable Care Act, such as introduction of the Hospital Readmission Reduction Program,” said Dr. Raval and Dr. Vyas.
SOURCE: Amit R et al. J Rheumatol. 2018 Jan 15. doi: 10.3899/jrheum.170368.
but the rise in proportion of the arthritis patients in the U.S. population led to billions more dollars being spent on this population, reported Amit D. Raval, PhD, and Ami Vyas, PhD, of the University of Rhode Island, Kingston.
Aggregate expenditures for patients with arthritis rose from $584.8 billion in 2008 to $645 billion in 2014, accounting for about 4% of the U.S. gross domestic product in these years, the investigators reported in the Journal of Rheumatology. “The increase in aggregate unadjusted total direct health care expenditures was mainly driven through an increase in weighted population of individuals with arthritis,” which rose from 56.1 million adults with arthritis in 2008 to 65.1 million in 2014. Nonetheless, there was a “slowdown in the intensity of adjusted incremental expenditures and [out of pocket expenditures] specifically from 2013, which led to a huge decline in the aggregate direct healthcare expenditures in 2014.”
During this time period, there was an increase in the percentage of Hispanics, poor, obese, and individuals with activity limitations and mental health disorders among both those with and without arthritis. This is consistent with the study findings that incremental health care expenditures in persons with arthritis were largely driven by difference in age, health status, and chronic conditions, such as hypertension, hyperlipidemia, and heart disease, among those with and without arthritis, Dr. Raval and Dr. Vyas said.
Annual total health care expenditures in persons with arthritis fell from $10,424 in 2008 to $9,910 in 2014. The average annual total out-of-pocket expenditures in 2008 was $1,493, which was 14% of total health care expenditures that year; in 2014, this fell to $1,099. There were similar trends in persons without arthritis, Dr. Raval and Dr. Vyas reported.
The top three expenditure categories in 2008 were outpatient (32.6%), inpatient (29.0%), and prescription drug costs (24.7%); in 2014, these changed to outpatient (33.8%), prescription drug (26.8%), and inpatient costs (26.4%). There are a number of ways to explain these trends, the researchers said. It is likely that outpatient services, such as outpatient orthopedic surgeries, are becoming “a common management option for arthritis.” Also, outpatient medication services now may include administration of injectables such as biologics. There also were “relatively stable” inpatient expenditures from 2008 to 2013 and a decline in 2014. “Our findings are consistent with studies assessing the effect of the Affordable Care Act, such as introduction of the Hospital Readmission Reduction Program,” said Dr. Raval and Dr. Vyas.
SOURCE: Amit R et al. J Rheumatol. 2018 Jan 15. doi: 10.3899/jrheum.170368.
FROM JOURNAL OF RHEUMATOLOGY
Key clinical point: The annual direct health care expenditures per person with arthritis remained relatively stable over the years 2008 to 2014.
Major finding: Aggregate expenditures for patients with arthritis rose from $584.8 billion in 2008 to $645 billion in 2014.
Study details: Medical Expenditure Panel Survey (MEPS) data from approximately 5,000-6,000 persons aged 18 years and older with arthritis each year during 2008-2014 and approximately 17,000-20,000 persons without arthritis each year during that period.
Disclosures: No information on relevant financial disclosures was evident.
Source: Amit R et al. J Rheumatol. 2018 Jan 15. doi: 10.3899/jrheum.170368.
Sprifermin shows cartilage-building potential in knee OA patients
in the initial 2-year results of the ongoing FORWARD trial.
“Sprifermin appears to be the first investigational medicinal product to show dose-dependent prevention of cartilage loss and an increase in cartilage thickness, not only in the total tibiofemoral joint [TFJ] but also in both the medial and lateral compartments, including the central medial femorotibial region,” said Marc H. Hochberg, MD, primary investigator in the trial and division head of rheumatology and clinical immunology at the University of Maryland, Baltimore. “The recommendation is that these findings should be further evaluated in phase 3 clinical trials.”
He and his colleagues randomized 549 osteoarthritis (OA) patients to double-blind treatment with one of four different dosing regimens of sprifermin or placebo. These patients were aged 40-85 with symptomatic radiographic primary femorotibial knee OA measuring grade 2 or 3 on the Kellgren-Lawrence scale and a medial minimum joint space width (mJSW) 2.5 mm or greater.
At 2 years, researchers observed a significant dose-dependent relationship between the amount of sprifermin given and the increase in total TFJ cartilage thickness. Patients who received three 100-mcg intra-articular injections of sprifermin every 6 months (group 1) showed a gain in TFJ cartilage thickness of 0.03 mm as seen on MRI, while those who received three 100-mcg injections of sprifermin every 12 months (group 2) had a gain of 0.02 mm, Dr. Hochberg said during a late-breaking abstract session at the annual meeting of the American College of Rheumatology. By contrast, those who received placebo had a loss in TFJ cartilage thickness of 0.02 mm (P less than .001). The other two groups received 30 mcg of sprifermin in three weekly injections every 6 months (group 3) or every 12 months (group 4), and these had TFJ cartilage thickness losses of about 0.01 mm or less.
Similar dose-dependent relationships were observed for some of the secondary endpoints, which included changes in cartilage thickness seen in the medial and lateral compartments, changes in cartilage thickness in the compartments’ subregions, and changes in mJSW. Significant differences in cartilage thickness were observed between sprifermin treatment groups and placebo in the medial (group 1, gain of 0.02 mm vs. loss of 0.03 mm; P less than .001) and lateral (groups 1 and 2, gain of 0.04 mm vs. loss of 0.01 mm; P less than .001) TFJ compartments, and in central medial and lateral TFJ subregions.
Changes in mJSW as seen on x-ray between those in group 1 and those on placebo were significant for the lateral compartment, with an increase in mJSW at the higher doses and a decline in the placebo group, but not for the medial compartment.
There were no significant differences in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores among the treatment groups. Dr. Hochberg noted that patients were permitted to take pain medications during the study, which could have affected this result.
The most frequently reported adverse events were musculoskeletal and connective tissue disorders, specifically arthralgias and back pain, Dr. Hochberg said. The incidence of acute inflammatory reactions was higher with sprifermin, compared with placebo, but the increase was only significant after the first injection cycle, he said.
Merck KGaA and the EMD Serono Research Institute funded the study. Dr. Hochberg reported receiving consulting fees from numerous companies that market or are developing OA drugs, including EMD Serono.
in the initial 2-year results of the ongoing FORWARD trial.
“Sprifermin appears to be the first investigational medicinal product to show dose-dependent prevention of cartilage loss and an increase in cartilage thickness, not only in the total tibiofemoral joint [TFJ] but also in both the medial and lateral compartments, including the central medial femorotibial region,” said Marc H. Hochberg, MD, primary investigator in the trial and division head of rheumatology and clinical immunology at the University of Maryland, Baltimore. “The recommendation is that these findings should be further evaluated in phase 3 clinical trials.”
He and his colleagues randomized 549 osteoarthritis (OA) patients to double-blind treatment with one of four different dosing regimens of sprifermin or placebo. These patients were aged 40-85 with symptomatic radiographic primary femorotibial knee OA measuring grade 2 or 3 on the Kellgren-Lawrence scale and a medial minimum joint space width (mJSW) 2.5 mm or greater.
At 2 years, researchers observed a significant dose-dependent relationship between the amount of sprifermin given and the increase in total TFJ cartilage thickness. Patients who received three 100-mcg intra-articular injections of sprifermin every 6 months (group 1) showed a gain in TFJ cartilage thickness of 0.03 mm as seen on MRI, while those who received three 100-mcg injections of sprifermin every 12 months (group 2) had a gain of 0.02 mm, Dr. Hochberg said during a late-breaking abstract session at the annual meeting of the American College of Rheumatology. By contrast, those who received placebo had a loss in TFJ cartilage thickness of 0.02 mm (P less than .001). The other two groups received 30 mcg of sprifermin in three weekly injections every 6 months (group 3) or every 12 months (group 4), and these had TFJ cartilage thickness losses of about 0.01 mm or less.
Similar dose-dependent relationships were observed for some of the secondary endpoints, which included changes in cartilage thickness seen in the medial and lateral compartments, changes in cartilage thickness in the compartments’ subregions, and changes in mJSW. Significant differences in cartilage thickness were observed between sprifermin treatment groups and placebo in the medial (group 1, gain of 0.02 mm vs. loss of 0.03 mm; P less than .001) and lateral (groups 1 and 2, gain of 0.04 mm vs. loss of 0.01 mm; P less than .001) TFJ compartments, and in central medial and lateral TFJ subregions.
Changes in mJSW as seen on x-ray between those in group 1 and those on placebo were significant for the lateral compartment, with an increase in mJSW at the higher doses and a decline in the placebo group, but not for the medial compartment.
There were no significant differences in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores among the treatment groups. Dr. Hochberg noted that patients were permitted to take pain medications during the study, which could have affected this result.
The most frequently reported adverse events were musculoskeletal and connective tissue disorders, specifically arthralgias and back pain, Dr. Hochberg said. The incidence of acute inflammatory reactions was higher with sprifermin, compared with placebo, but the increase was only significant after the first injection cycle, he said.
Merck KGaA and the EMD Serono Research Institute funded the study. Dr. Hochberg reported receiving consulting fees from numerous companies that market or are developing OA drugs, including EMD Serono.
in the initial 2-year results of the ongoing FORWARD trial.
“Sprifermin appears to be the first investigational medicinal product to show dose-dependent prevention of cartilage loss and an increase in cartilage thickness, not only in the total tibiofemoral joint [TFJ] but also in both the medial and lateral compartments, including the central medial femorotibial region,” said Marc H. Hochberg, MD, primary investigator in the trial and division head of rheumatology and clinical immunology at the University of Maryland, Baltimore. “The recommendation is that these findings should be further evaluated in phase 3 clinical trials.”
He and his colleagues randomized 549 osteoarthritis (OA) patients to double-blind treatment with one of four different dosing regimens of sprifermin or placebo. These patients were aged 40-85 with symptomatic radiographic primary femorotibial knee OA measuring grade 2 or 3 on the Kellgren-Lawrence scale and a medial minimum joint space width (mJSW) 2.5 mm or greater.
At 2 years, researchers observed a significant dose-dependent relationship between the amount of sprifermin given and the increase in total TFJ cartilage thickness. Patients who received three 100-mcg intra-articular injections of sprifermin every 6 months (group 1) showed a gain in TFJ cartilage thickness of 0.03 mm as seen on MRI, while those who received three 100-mcg injections of sprifermin every 12 months (group 2) had a gain of 0.02 mm, Dr. Hochberg said during a late-breaking abstract session at the annual meeting of the American College of Rheumatology. By contrast, those who received placebo had a loss in TFJ cartilage thickness of 0.02 mm (P less than .001). The other two groups received 30 mcg of sprifermin in three weekly injections every 6 months (group 3) or every 12 months (group 4), and these had TFJ cartilage thickness losses of about 0.01 mm or less.
Similar dose-dependent relationships were observed for some of the secondary endpoints, which included changes in cartilage thickness seen in the medial and lateral compartments, changes in cartilage thickness in the compartments’ subregions, and changes in mJSW. Significant differences in cartilage thickness were observed between sprifermin treatment groups and placebo in the medial (group 1, gain of 0.02 mm vs. loss of 0.03 mm; P less than .001) and lateral (groups 1 and 2, gain of 0.04 mm vs. loss of 0.01 mm; P less than .001) TFJ compartments, and in central medial and lateral TFJ subregions.
Changes in mJSW as seen on x-ray between those in group 1 and those on placebo were significant for the lateral compartment, with an increase in mJSW at the higher doses and a decline in the placebo group, but not for the medial compartment.
There were no significant differences in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores among the treatment groups. Dr. Hochberg noted that patients were permitted to take pain medications during the study, which could have affected this result.
The most frequently reported adverse events were musculoskeletal and connective tissue disorders, specifically arthralgias and back pain, Dr. Hochberg said. The incidence of acute inflammatory reactions was higher with sprifermin, compared with placebo, but the increase was only significant after the first injection cycle, he said.
Merck KGaA and the EMD Serono Research Institute funded the study. Dr. Hochberg reported receiving consulting fees from numerous companies that market or are developing OA drugs, including EMD Serono.
REPORTING FROM ACR 2017
Key clinical point: Sprifermin may help build knee joint cartilage in patients with OA.
Major finding: Patients taking sprifermin 100 mcg three times a week every 6 months or every 12 months had gains in tibiofemoral joint cartilage thickness of 0.03 mm and 0.02 mm, respectively, over a 2-year period.
Study details: A study of 549 patients with symptomatic knee OA randomized to receive either 30 mcg or 100 mcg of sprifermin three times a week every 6 or every 12 months, or placebo.
Disclosures: Merck KGaA and the EMD Serono Research Institute funded the study. The presenter reported receiving consulting fees from numerous companies that market or are developing OA drugs, including EMD Serono.
Source: Hochberg M et al. ACR 2017 abstract 1L.
Evidence builds for long-term ineffectiveness of steroid shots for knee OA
SAN DIEGO – Real-world, nontrial research confirms the findings of a high-profile study released earlier in 2017: Corticosteroid shots are ineffective in the long term for knee osteoarthritis. In fact, researchers found a greater likelihood of a worsening condition in knees treated with the injections.
“Our findings are consistent with the latest randomized, controlled trial,” said study coauthor Jie Wei, MD, of Central South University in Changsha, China. She spoke in a plenary presentation about the study findings at the annual meeting of the American College of Rheumatology.
The use of corticosteroids for knee OA is a controversial topic. As Dr. Wei noted, there has been wide disagreement among medical societies about whether the treatment is useful in the long term for patients with pain flare-ups.
For the randomized, controlled study released in 2017, researchers tracked 140 patients aged 45 and older with inflammation of the synovial membrane. They were randomly assigned to injections of intra-articular triamcinolone or a placebo.
After 2 years of injections every 12 weeks, there was no difference in reported pain between the intervention and control groups. Also, those who received injections lost more cartilage (JAMA. 2017 May 16;317[19]:1967-75).
Researchers launched the new study to seek insight through a real-life cohort. They examined findings from the Osteoarthritis Initiative, a longitudinal study of 4,796 patients aged 45-79 at four U.S. clinics with knee OA or high risk of knee OA. Patients underwent annual examinations at baseline and annually for 4 years.
In an adjusted marginal structural analysis, knee replacement or worsening of Kellgren Lawrence grade at the tibial femoral joint was more likely in 149 injection knees than 2,191 noninjection knees (odds ratio, 5.74; 95% confidence interval, 2.01-16.42).
Knee replacement or joint space width worsening at the tibial femoral joint was also more likely in 120 injection knees than 2,112 noninjection knees (OR, 1.64; 95% CI, 0.91-2.93).
In another analysis, researchers tracked 134 injection knees (58 whose OA progressed) and 498 noninjection knees (132 whose OA progressed) for up to 8 years. After adjustment, the injection knees were more likely to have progressed (hazard ratio, 1.60; 95% CI, 1.21-2.12,).
“Several explanations may account for our study findings,” Dr. Wei said. One possibility, she said, is that corticosteroids may hurt chondrocytes by, among other things, inducing apoptosis and synovial membrane inflammation.
It’s also possible, she said, that patients may feel pain relief after injections and subsequently boost the risk of OA progression by increasing their physical activity.
“We need to know what types of physical activities may increase the OA progression,” she said. “Did patients who received steroid injection indeed increase this type of physical activity compared to subjects without steroid injection?”
Dr. Wei noted the study’s limitations, including the fact that patients who received injections had more pain at baseline, potentially indicating they had worse structural lesions that are more susceptible to progression.
The study authors reported no relevant disclosures. The National Natural Science Foundation of China funded the study. The Osteoarthritis Initiative is a partnership between the National Institutes of Health and Merck, Novartis, GlaxoSmithKline, and Pfizer.
SAN DIEGO – Real-world, nontrial research confirms the findings of a high-profile study released earlier in 2017: Corticosteroid shots are ineffective in the long term for knee osteoarthritis. In fact, researchers found a greater likelihood of a worsening condition in knees treated with the injections.
“Our findings are consistent with the latest randomized, controlled trial,” said study coauthor Jie Wei, MD, of Central South University in Changsha, China. She spoke in a plenary presentation about the study findings at the annual meeting of the American College of Rheumatology.
The use of corticosteroids for knee OA is a controversial topic. As Dr. Wei noted, there has been wide disagreement among medical societies about whether the treatment is useful in the long term for patients with pain flare-ups.
For the randomized, controlled study released in 2017, researchers tracked 140 patients aged 45 and older with inflammation of the synovial membrane. They were randomly assigned to injections of intra-articular triamcinolone or a placebo.
After 2 years of injections every 12 weeks, there was no difference in reported pain between the intervention and control groups. Also, those who received injections lost more cartilage (JAMA. 2017 May 16;317[19]:1967-75).
Researchers launched the new study to seek insight through a real-life cohort. They examined findings from the Osteoarthritis Initiative, a longitudinal study of 4,796 patients aged 45-79 at four U.S. clinics with knee OA or high risk of knee OA. Patients underwent annual examinations at baseline and annually for 4 years.
In an adjusted marginal structural analysis, knee replacement or worsening of Kellgren Lawrence grade at the tibial femoral joint was more likely in 149 injection knees than 2,191 noninjection knees (odds ratio, 5.74; 95% confidence interval, 2.01-16.42).
Knee replacement or joint space width worsening at the tibial femoral joint was also more likely in 120 injection knees than 2,112 noninjection knees (OR, 1.64; 95% CI, 0.91-2.93).
In another analysis, researchers tracked 134 injection knees (58 whose OA progressed) and 498 noninjection knees (132 whose OA progressed) for up to 8 years. After adjustment, the injection knees were more likely to have progressed (hazard ratio, 1.60; 95% CI, 1.21-2.12,).
“Several explanations may account for our study findings,” Dr. Wei said. One possibility, she said, is that corticosteroids may hurt chondrocytes by, among other things, inducing apoptosis and synovial membrane inflammation.
It’s also possible, she said, that patients may feel pain relief after injections and subsequently boost the risk of OA progression by increasing their physical activity.
“We need to know what types of physical activities may increase the OA progression,” she said. “Did patients who received steroid injection indeed increase this type of physical activity compared to subjects without steroid injection?”
Dr. Wei noted the study’s limitations, including the fact that patients who received injections had more pain at baseline, potentially indicating they had worse structural lesions that are more susceptible to progression.
The study authors reported no relevant disclosures. The National Natural Science Foundation of China funded the study. The Osteoarthritis Initiative is a partnership between the National Institutes of Health and Merck, Novartis, GlaxoSmithKline, and Pfizer.
SAN DIEGO – Real-world, nontrial research confirms the findings of a high-profile study released earlier in 2017: Corticosteroid shots are ineffective in the long term for knee osteoarthritis. In fact, researchers found a greater likelihood of a worsening condition in knees treated with the injections.
“Our findings are consistent with the latest randomized, controlled trial,” said study coauthor Jie Wei, MD, of Central South University in Changsha, China. She spoke in a plenary presentation about the study findings at the annual meeting of the American College of Rheumatology.
The use of corticosteroids for knee OA is a controversial topic. As Dr. Wei noted, there has been wide disagreement among medical societies about whether the treatment is useful in the long term for patients with pain flare-ups.
For the randomized, controlled study released in 2017, researchers tracked 140 patients aged 45 and older with inflammation of the synovial membrane. They were randomly assigned to injections of intra-articular triamcinolone or a placebo.
After 2 years of injections every 12 weeks, there was no difference in reported pain between the intervention and control groups. Also, those who received injections lost more cartilage (JAMA. 2017 May 16;317[19]:1967-75).
Researchers launched the new study to seek insight through a real-life cohort. They examined findings from the Osteoarthritis Initiative, a longitudinal study of 4,796 patients aged 45-79 at four U.S. clinics with knee OA or high risk of knee OA. Patients underwent annual examinations at baseline and annually for 4 years.
In an adjusted marginal structural analysis, knee replacement or worsening of Kellgren Lawrence grade at the tibial femoral joint was more likely in 149 injection knees than 2,191 noninjection knees (odds ratio, 5.74; 95% confidence interval, 2.01-16.42).
Knee replacement or joint space width worsening at the tibial femoral joint was also more likely in 120 injection knees than 2,112 noninjection knees (OR, 1.64; 95% CI, 0.91-2.93).
In another analysis, researchers tracked 134 injection knees (58 whose OA progressed) and 498 noninjection knees (132 whose OA progressed) for up to 8 years. After adjustment, the injection knees were more likely to have progressed (hazard ratio, 1.60; 95% CI, 1.21-2.12,).
“Several explanations may account for our study findings,” Dr. Wei said. One possibility, she said, is that corticosteroids may hurt chondrocytes by, among other things, inducing apoptosis and synovial membrane inflammation.
It’s also possible, she said, that patients may feel pain relief after injections and subsequently boost the risk of OA progression by increasing their physical activity.
“We need to know what types of physical activities may increase the OA progression,” she said. “Did patients who received steroid injection indeed increase this type of physical activity compared to subjects without steroid injection?”
Dr. Wei noted the study’s limitations, including the fact that patients who received injections had more pain at baseline, potentially indicating they had worse structural lesions that are more susceptible to progression.
The study authors reported no relevant disclosures. The National Natural Science Foundation of China funded the study. The Osteoarthritis Initiative is a partnership between the National Institutes of Health and Merck, Novartis, GlaxoSmithKline, and Pfizer.
REPORTING FROM ACR 2017
Key clinical point:
Major finding: In adjusted analysis of 134 injection knees and 498 noninjection knees tracked for up to 8 years, OA in injection knees was more likely to have progressed (HR, 1.60; 95% CI, 1.21-2.12).
Study details: Cohort analysis of data from the Osteoarthritis Initiative, which tracked patients with (or at high risk of) knee OA at four U.S. clinics.
Disclosures: The study authors reported no relevant disclosures. The National Natural Science Foundation of China funded the study. The Osteoarthritis Initiative is a partnership between the National Institutes of Health and Merck, Novartis, GlaxoSmithKline, and Pfizer.
Source: Lei G et al. ACR 2017 Abstract 1788.