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EMA: Stop high-dose Xeljanz in certain patients
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency has recommended that patients at high risk of blood clots in the lungs should not be prescribed the 10-mg, twice-daily dose of tofacitinib (Xeljanz).
The PRAC recommendation is based on results from an ongoing study of patients with rheumatoid arthritis (RA), which has shown that patients receiving the 10-mg, twice-daily dose – twice the approved dose for RA – are at an increased risk of blood clots in the lungs and death.
Patients at risk include those with heart failure, cancer, inherited blood clotting disorders, or a history of blood clots, as well as patients who take combined hormonal contraceptives, are receiving hormone replacement therapy, or are undergoing major surgery. In addition, age, obesity, smoking, or immobilization should also be considered as risk factors.
In Europe, tofacitinib is indicated for the treatment of RA, psoriatic arthritis, and severe ulcerative colitis. Because the 10-mg dose is the only indicated treatment for ulcerative colitis, patients with the disease and who are at high risk should not be started on tofacitinib, and patients who are already taking the drug should be switched to a different treatment.
“The new recommendations are temporary and follow previous PRAC advice not to exceed the recommended 5-mg, twice-daily dose when treating rheumatoid arthritis. The PRAC will now carry out a review of all available evidence, and updated guidance will be provided to patients and healthcare professionals once the review is concluded,” according to the European Medicines Agency.
Find the full press release on the European Medicines Agency website.
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency has recommended that patients at high risk of blood clots in the lungs should not be prescribed the 10-mg, twice-daily dose of tofacitinib (Xeljanz).
The PRAC recommendation is based on results from an ongoing study of patients with rheumatoid arthritis (RA), which has shown that patients receiving the 10-mg, twice-daily dose – twice the approved dose for RA – are at an increased risk of blood clots in the lungs and death.
Patients at risk include those with heart failure, cancer, inherited blood clotting disorders, or a history of blood clots, as well as patients who take combined hormonal contraceptives, are receiving hormone replacement therapy, or are undergoing major surgery. In addition, age, obesity, smoking, or immobilization should also be considered as risk factors.
In Europe, tofacitinib is indicated for the treatment of RA, psoriatic arthritis, and severe ulcerative colitis. Because the 10-mg dose is the only indicated treatment for ulcerative colitis, patients with the disease and who are at high risk should not be started on tofacitinib, and patients who are already taking the drug should be switched to a different treatment.
“The new recommendations are temporary and follow previous PRAC advice not to exceed the recommended 5-mg, twice-daily dose when treating rheumatoid arthritis. The PRAC will now carry out a review of all available evidence, and updated guidance will be provided to patients and healthcare professionals once the review is concluded,” according to the European Medicines Agency.
Find the full press release on the European Medicines Agency website.
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency has recommended that patients at high risk of blood clots in the lungs should not be prescribed the 10-mg, twice-daily dose of tofacitinib (Xeljanz).
The PRAC recommendation is based on results from an ongoing study of patients with rheumatoid arthritis (RA), which has shown that patients receiving the 10-mg, twice-daily dose – twice the approved dose for RA – are at an increased risk of blood clots in the lungs and death.
Patients at risk include those with heart failure, cancer, inherited blood clotting disorders, or a history of blood clots, as well as patients who take combined hormonal contraceptives, are receiving hormone replacement therapy, or are undergoing major surgery. In addition, age, obesity, smoking, or immobilization should also be considered as risk factors.
In Europe, tofacitinib is indicated for the treatment of RA, psoriatic arthritis, and severe ulcerative colitis. Because the 10-mg dose is the only indicated treatment for ulcerative colitis, patients with the disease and who are at high risk should not be started on tofacitinib, and patients who are already taking the drug should be switched to a different treatment.
“The new recommendations are temporary and follow previous PRAC advice not to exceed the recommended 5-mg, twice-daily dose when treating rheumatoid arthritis. The PRAC will now carry out a review of all available evidence, and updated guidance will be provided to patients and healthcare professionals once the review is concluded,” according to the European Medicines Agency.
Find the full press release on the European Medicines Agency website.
High-intensity statins may cut risk of joint replacement
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
REPORTING FROM OARSI 2019
Key clinical point: High-intensity statin therapy may reduce need for joint replacement in arthritis.
Major finding: The risk of knee or hip replacement surgery for rheumatoid arthritis was slashed by 90%, and by 21% for osteoarthritis.
Study details: This study included nearly 180,000 statin users propensity score-matched to an equal number of nonusers and prospectively followed for a mean of 6.5 years.
Disclosures: The study was supported by the National Clinical Research Center of Geriatric Disorders at Central South University in Hunan, China, and by several British universities. The presenter reported having no financial conflicts of interest.
Source: Sarmanova A et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
VA system lags in getting DMARDs to veterans with inflammatory arthritis
MADISON, WISC. – Only half of United States veterans with inflammatory arthritis received disease-modifying medication within 90 days of diagnosis if they received care within the Veterans Health Administration, according to a study presented at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Over the study period, 58.2% of all inflammatory arthritis patients began a disease-modifying antirheumatic drug (DMARD) within 12 months of diagnosis. Rates of DMARD initiation were similar for patients with rheumatoid arthritis (RA, 57.7%) and psoriatic arthritis (PsA, 64.3%), said the first author of the poster presentation, Sogol S. Amjadi, DO, a resident physician at Bingham Memorial Hospital, Blackfoot, Idaho.
However, at 12 months after diagnosis, only 29.6% of ankylosing spondylitis (AS) patients had not been started on a DMARD. “The ankylosing spondylitis group really had the lowest DMARD initiation over time,” said Dr. Amjadi in an interview.
The study used diagnosis codes and natural language processing to look for incident cases of the three inflammatory arthritides (IAs) among patients receiving care within the Veterans Health Administration from 2007 through 2015.
In all, 12,118 patients with incident IA were identified. Of these, 9,711 had RA, 1,472 had PsA, and 935 had AS. Patients were mostly (91.3%) male, with a mean age of 63.7 years.
Over the study period, 41.2% of IA patients were dispensed a DMARD within 30 days of diagnosis, and 50% received a DMARD within 90 days of diagnosis. Patients with PsA or RA had similar rates of DMARD prescription within 30 days of diagnosis (about 42% and 43%, respectively).
The investigators discovered in their analysis that another factor in prompt treatment was access to specialty care.“Timely access to a rheumatology provider is likely important for early DMARD treatment,” wrote Dr. Amjadi and her coauthors in the poster accompanying the presentation. Of patients who did receive a DMARD, 82.7% had received rheumatology specialty care before nonbiologic DMARD dispensing, as had 90.0% of patients receiving biologic DMARDs. Over the entire study period, about 10% of all IA patients had biologic DMARD exposure.
There was a trend over time for increased DMARD dispensing, said the investigators. “The percentage of IA patients with DMARD exposure during the 12-month follow-up period increased from 48.8% in 2008 to 66.4% in 2015.”
For AS patients, early DMARD prescribing rates rose from about 20% in 2007 to nearly 30% in 2015. “DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but nontreatment remained common, particularly in patients with AS,” wrote the investigators. “Delays in treatment for inflammatory arthritis are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability.”
The authors reported no conflicts of interest and no outside sources of funding.
MADISON, WISC. – Only half of United States veterans with inflammatory arthritis received disease-modifying medication within 90 days of diagnosis if they received care within the Veterans Health Administration, according to a study presented at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Over the study period, 58.2% of all inflammatory arthritis patients began a disease-modifying antirheumatic drug (DMARD) within 12 months of diagnosis. Rates of DMARD initiation were similar for patients with rheumatoid arthritis (RA, 57.7%) and psoriatic arthritis (PsA, 64.3%), said the first author of the poster presentation, Sogol S. Amjadi, DO, a resident physician at Bingham Memorial Hospital, Blackfoot, Idaho.
However, at 12 months after diagnosis, only 29.6% of ankylosing spondylitis (AS) patients had not been started on a DMARD. “The ankylosing spondylitis group really had the lowest DMARD initiation over time,” said Dr. Amjadi in an interview.
The study used diagnosis codes and natural language processing to look for incident cases of the three inflammatory arthritides (IAs) among patients receiving care within the Veterans Health Administration from 2007 through 2015.
In all, 12,118 patients with incident IA were identified. Of these, 9,711 had RA, 1,472 had PsA, and 935 had AS. Patients were mostly (91.3%) male, with a mean age of 63.7 years.
Over the study period, 41.2% of IA patients were dispensed a DMARD within 30 days of diagnosis, and 50% received a DMARD within 90 days of diagnosis. Patients with PsA or RA had similar rates of DMARD prescription within 30 days of diagnosis (about 42% and 43%, respectively).
The investigators discovered in their analysis that another factor in prompt treatment was access to specialty care.“Timely access to a rheumatology provider is likely important for early DMARD treatment,” wrote Dr. Amjadi and her coauthors in the poster accompanying the presentation. Of patients who did receive a DMARD, 82.7% had received rheumatology specialty care before nonbiologic DMARD dispensing, as had 90.0% of patients receiving biologic DMARDs. Over the entire study period, about 10% of all IA patients had biologic DMARD exposure.
There was a trend over time for increased DMARD dispensing, said the investigators. “The percentage of IA patients with DMARD exposure during the 12-month follow-up period increased from 48.8% in 2008 to 66.4% in 2015.”
For AS patients, early DMARD prescribing rates rose from about 20% in 2007 to nearly 30% in 2015. “DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but nontreatment remained common, particularly in patients with AS,” wrote the investigators. “Delays in treatment for inflammatory arthritis are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability.”
The authors reported no conflicts of interest and no outside sources of funding.
MADISON, WISC. – Only half of United States veterans with inflammatory arthritis received disease-modifying medication within 90 days of diagnosis if they received care within the Veterans Health Administration, according to a study presented at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Over the study period, 58.2% of all inflammatory arthritis patients began a disease-modifying antirheumatic drug (DMARD) within 12 months of diagnosis. Rates of DMARD initiation were similar for patients with rheumatoid arthritis (RA, 57.7%) and psoriatic arthritis (PsA, 64.3%), said the first author of the poster presentation, Sogol S. Amjadi, DO, a resident physician at Bingham Memorial Hospital, Blackfoot, Idaho.
However, at 12 months after diagnosis, only 29.6% of ankylosing spondylitis (AS) patients had not been started on a DMARD. “The ankylosing spondylitis group really had the lowest DMARD initiation over time,” said Dr. Amjadi in an interview.
The study used diagnosis codes and natural language processing to look for incident cases of the three inflammatory arthritides (IAs) among patients receiving care within the Veterans Health Administration from 2007 through 2015.
In all, 12,118 patients with incident IA were identified. Of these, 9,711 had RA, 1,472 had PsA, and 935 had AS. Patients were mostly (91.3%) male, with a mean age of 63.7 years.
Over the study period, 41.2% of IA patients were dispensed a DMARD within 30 days of diagnosis, and 50% received a DMARD within 90 days of diagnosis. Patients with PsA or RA had similar rates of DMARD prescription within 30 days of diagnosis (about 42% and 43%, respectively).
The investigators discovered in their analysis that another factor in prompt treatment was access to specialty care.“Timely access to a rheumatology provider is likely important for early DMARD treatment,” wrote Dr. Amjadi and her coauthors in the poster accompanying the presentation. Of patients who did receive a DMARD, 82.7% had received rheumatology specialty care before nonbiologic DMARD dispensing, as had 90.0% of patients receiving biologic DMARDs. Over the entire study period, about 10% of all IA patients had biologic DMARD exposure.
There was a trend over time for increased DMARD dispensing, said the investigators. “The percentage of IA patients with DMARD exposure during the 12-month follow-up period increased from 48.8% in 2008 to 66.4% in 2015.”
For AS patients, early DMARD prescribing rates rose from about 20% in 2007 to nearly 30% in 2015. “DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but nontreatment remained common, particularly in patients with AS,” wrote the investigators. “Delays in treatment for inflammatory arthritis are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability.”
The authors reported no conflicts of interest and no outside sources of funding.
REPORTING FROM SPARTAN 2019
Key clinical point:
Major finding: Overall, 58.2% of inflammatory arthritis patients received a DMARD within the first year of diagnosis.
Study details: Retrospective review of 12,118 incident cases of inflammatory arthritis in the Veterans Health Administration during the period from 2007 through 2015.
Disclosures: The authors reported no conflicts of interest and no outside sources of funding.
Source: Amjadi SS et al. SPARTAN 2019.
Higher infection risk in RA seen with high blood biologic levels
BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.
Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.
There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.
“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).
The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.
According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.
Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.
In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.
Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).
In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.
The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.
As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.
Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.
Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”
Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.
Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.
Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”
When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”
The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.
In this study, the authors use the major British Society for Rheumatology Biologics Register – Rheumatoid Arthritis and examine infections and serious infections across biologics. They define “low/normal” blood levels versus “high” blood levels based on concentration-effect curves. Examining data censored at 1 year versus incidence during 1 year, the results are somewhat inconsistent. With larger numbers available for data censored at 1 year, there is some increased risk using hazard ratios for both all infections and serious infections. With smaller numbers for incident infections during the first year, this hazard ratio does not show an effect.
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also practices part-time in Los Angeles and Seattle.
In this study, the authors use the major British Society for Rheumatology Biologics Register – Rheumatoid Arthritis and examine infections and serious infections across biologics. They define “low/normal” blood levels versus “high” blood levels based on concentration-effect curves. Examining data censored at 1 year versus incidence during 1 year, the results are somewhat inconsistent. With larger numbers available for data censored at 1 year, there is some increased risk using hazard ratios for both all infections and serious infections. With smaller numbers for incident infections during the first year, this hazard ratio does not show an effect.
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also practices part-time in Los Angeles and Seattle.
In this study, the authors use the major British Society for Rheumatology Biologics Register – Rheumatoid Arthritis and examine infections and serious infections across biologics. They define “low/normal” blood levels versus “high” blood levels based on concentration-effect curves. Examining data censored at 1 year versus incidence during 1 year, the results are somewhat inconsistent. With larger numbers available for data censored at 1 year, there is some increased risk using hazard ratios for both all infections and serious infections. With smaller numbers for incident infections during the first year, this hazard ratio does not show an effect.
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also practices part-time in Los Angeles and Seattle.
BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.
Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.
There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.
“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).
The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.
According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.
Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.
In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.
Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).
In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.
The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.
As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.
Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.
Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”
Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.
Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.
Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”
When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”
The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.
BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.
Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.
There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.
“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).
The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.
According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.
Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.
In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.
Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).
In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.
The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.
As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.
Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.
Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”
Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.
Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.
Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”
When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”
The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.
REPORTING FROM BSR 2019
Arthritis joint pain, inactivity vary greatly across U.S.
Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.
Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).
The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.
The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.
“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”
SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.
Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.
Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).
The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.
The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.
“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”
SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.
Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.
Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).
The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.
The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.
“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”
SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.
FROM MMWR
Study compares tapering strategies in rheumatoid arthritis
Patients whose rheumatoid arthritis was in sustained remission had similar rates of flare for the first 9 months after they tapered off either their conventional synthetic disease-modifying antirheumatic drug (DMARD), or their tumor necrosis factor (TNF) inhibitor, researchers reported.
After the first year, first author Elise van Mulligen of Erasmus University Medical Center in Rotterdam, the Netherlands, and her associates found that flares rates were 10% lower among patients who first tapered conventional synthetic DMARDs, a difference that was not statistically significant. Because secondary endpoints also were similar between groups, patients should consider first tapering off their TNF inhibitor to save costs and reduce side effects, the researchers wrote in Annals of the Rheumatic Diseases.
Over the past decade, better drugs, treat-to-target approaches, and earlier disease detection have vastly improved outcomes in rheumatoid arthritis. As more patients achieve sustained remission, they are tapering off therapy in accordance with current guidelines. This multicenter, single-blinded, randomized trial (Tapering Strategies in Rheumatoid Arthritis [TARA]) is one of the first to compare tapering strategies, rather than looking at only whether tapering is feasible.
The study included 189 patients from the Netherlands whose rheumatoid arthritis was in sustained remission (Disease Activity Score [DAS] less than 2.4 and swollen joint count less than 1 for at least 3 months) on a conventional synthetic DMARD plus a TNF inhibitor. Patients were randomly assigned to either halve the conventional synthetic DMARD dose, or to double the TNF-inhibitor dosing interval. After 3 months, they cut the dose of their assigned taper medication to 25% of baseline. If they stayed in remission, they stopped the medication 3 months later. They avoided glucocorticoids throughout.
There were no serious adverse events related to tapering. Cumulative rates of flare at 1 year (DAS greater than 2.4 or swollen joint count greater than 1) were 33% for conventional synthetic DMARD taper (95% confidence interval, 24%-43%) and 43% (95% CI, 33%-53%) for TNF-inhibitor taper (P = .17). The two groups also had similar scores at 1 year on the DAS, Health Assessment Questionnaire-Disability Index, and European Quality of Life-5 Dimensions index.
The suggestion to first taper off TNF inhibitors reflects current European League Against Rheumatism guidelines, which advise first tapering glucocorticoids, then biologic DMARDS, and finally conventional synthetic DMARDs. “Our results and the fact that TNF blockers are more expensive than conventional synthetic DMARDs support the aforementioned tapering order,” the researchers concluded.
An unrestricted grant from ZonMW supported the work. The investigators reported having no conflicts of interest.
SOURCE: Mulligen E et al. Ann Rheum Dis. 2019 Apr 6. doi: 10.1136/annrheumdis-2018-214970.
Patients whose rheumatoid arthritis was in sustained remission had similar rates of flare for the first 9 months after they tapered off either their conventional synthetic disease-modifying antirheumatic drug (DMARD), or their tumor necrosis factor (TNF) inhibitor, researchers reported.
After the first year, first author Elise van Mulligen of Erasmus University Medical Center in Rotterdam, the Netherlands, and her associates found that flares rates were 10% lower among patients who first tapered conventional synthetic DMARDs, a difference that was not statistically significant. Because secondary endpoints also were similar between groups, patients should consider first tapering off their TNF inhibitor to save costs and reduce side effects, the researchers wrote in Annals of the Rheumatic Diseases.
Over the past decade, better drugs, treat-to-target approaches, and earlier disease detection have vastly improved outcomes in rheumatoid arthritis. As more patients achieve sustained remission, they are tapering off therapy in accordance with current guidelines. This multicenter, single-blinded, randomized trial (Tapering Strategies in Rheumatoid Arthritis [TARA]) is one of the first to compare tapering strategies, rather than looking at only whether tapering is feasible.
The study included 189 patients from the Netherlands whose rheumatoid arthritis was in sustained remission (Disease Activity Score [DAS] less than 2.4 and swollen joint count less than 1 for at least 3 months) on a conventional synthetic DMARD plus a TNF inhibitor. Patients were randomly assigned to either halve the conventional synthetic DMARD dose, or to double the TNF-inhibitor dosing interval. After 3 months, they cut the dose of their assigned taper medication to 25% of baseline. If they stayed in remission, they stopped the medication 3 months later. They avoided glucocorticoids throughout.
There were no serious adverse events related to tapering. Cumulative rates of flare at 1 year (DAS greater than 2.4 or swollen joint count greater than 1) were 33% for conventional synthetic DMARD taper (95% confidence interval, 24%-43%) and 43% (95% CI, 33%-53%) for TNF-inhibitor taper (P = .17). The two groups also had similar scores at 1 year on the DAS, Health Assessment Questionnaire-Disability Index, and European Quality of Life-5 Dimensions index.
The suggestion to first taper off TNF inhibitors reflects current European League Against Rheumatism guidelines, which advise first tapering glucocorticoids, then biologic DMARDS, and finally conventional synthetic DMARDs. “Our results and the fact that TNF blockers are more expensive than conventional synthetic DMARDs support the aforementioned tapering order,” the researchers concluded.
An unrestricted grant from ZonMW supported the work. The investigators reported having no conflicts of interest.
SOURCE: Mulligen E et al. Ann Rheum Dis. 2019 Apr 6. doi: 10.1136/annrheumdis-2018-214970.
Patients whose rheumatoid arthritis was in sustained remission had similar rates of flare for the first 9 months after they tapered off either their conventional synthetic disease-modifying antirheumatic drug (DMARD), or their tumor necrosis factor (TNF) inhibitor, researchers reported.
After the first year, first author Elise van Mulligen of Erasmus University Medical Center in Rotterdam, the Netherlands, and her associates found that flares rates were 10% lower among patients who first tapered conventional synthetic DMARDs, a difference that was not statistically significant. Because secondary endpoints also were similar between groups, patients should consider first tapering off their TNF inhibitor to save costs and reduce side effects, the researchers wrote in Annals of the Rheumatic Diseases.
Over the past decade, better drugs, treat-to-target approaches, and earlier disease detection have vastly improved outcomes in rheumatoid arthritis. As more patients achieve sustained remission, they are tapering off therapy in accordance with current guidelines. This multicenter, single-blinded, randomized trial (Tapering Strategies in Rheumatoid Arthritis [TARA]) is one of the first to compare tapering strategies, rather than looking at only whether tapering is feasible.
The study included 189 patients from the Netherlands whose rheumatoid arthritis was in sustained remission (Disease Activity Score [DAS] less than 2.4 and swollen joint count less than 1 for at least 3 months) on a conventional synthetic DMARD plus a TNF inhibitor. Patients were randomly assigned to either halve the conventional synthetic DMARD dose, or to double the TNF-inhibitor dosing interval. After 3 months, they cut the dose of their assigned taper medication to 25% of baseline. If they stayed in remission, they stopped the medication 3 months later. They avoided glucocorticoids throughout.
There were no serious adverse events related to tapering. Cumulative rates of flare at 1 year (DAS greater than 2.4 or swollen joint count greater than 1) were 33% for conventional synthetic DMARD taper (95% confidence interval, 24%-43%) and 43% (95% CI, 33%-53%) for TNF-inhibitor taper (P = .17). The two groups also had similar scores at 1 year on the DAS, Health Assessment Questionnaire-Disability Index, and European Quality of Life-5 Dimensions index.
The suggestion to first taper off TNF inhibitors reflects current European League Against Rheumatism guidelines, which advise first tapering glucocorticoids, then biologic DMARDS, and finally conventional synthetic DMARDs. “Our results and the fact that TNF blockers are more expensive than conventional synthetic DMARDs support the aforementioned tapering order,” the researchers concluded.
An unrestricted grant from ZonMW supported the work. The investigators reported having no conflicts of interest.
SOURCE: Mulligen E et al. Ann Rheum Dis. 2019 Apr 6. doi: 10.1136/annrheumdis-2018-214970.
FROM ANNALS OF THE RHEUMATIC DISEASES
Interosseous tendon inflammation is common prior to RA
MAUI, HAWAII – Inflammation of the hand interosseous tendons found on MRI is a novel target in efforts to preempt the development and progression of rheumatoid arthritis, Paul Emery, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
He and his coinvestigators have previously shown there is a high prevalence of interosseous tendon inflammation in the hands of patients with established RA, but now they’ve demonstrated that this phenomenon also occurs in anti–cyclic citrullinated peptide (CCP)–positive individuals at increased risk for RA, even before onset of clinical synovitis.
This finding is consistent with the notion that, even though RA is classically considered a disease of the synovial joints, the joint involvement is a relatively late phenomenon in the disease development process and extracapsular structures may be important early targets of RA-related inflammation. Indeed, the MRI finding of tenosynovitis of the wrist and finger flexor tendons is known to be the strongest predictor of progression to arthritis in patients with recent-onset arthralgia or other musculoskeletal symptoms but no clinical synovitis, according to Dr. Emery, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Center.
Because the interosseous muscles of the hands play a critical role in hand function – pianists and other musicians not infrequently present to rheumatologists with overuse injuries of the muscles and their tendons – Dr. Emery and his coworkers decided to take a comprehensive look at interosseous tendon inflammation across the full spectrum of RA and pre-RA. They conducted a retrospective study of clinical and hand MRI data on 93 CCP-positive patients who presented with new-onset musculoskeletal symptoms but no clinical synovitis; 47 patients with early RA, all of whom were disease-modifying antirheumatic drug–naive; 28 patients with late RA as defined by at least 1 year of symptoms, anti-CCP and/or rheumatoid factor positivity, a Disease Activity Score in 28 joints (DAS28) of 3.2 or more, plus a history of exposure to one or more DMARDs at the time of their hand imaging; and 20 healthy controls.
The key finding is that the proportion of subjects with MRI evidence of interosseous tendon inflammation rose along the advancing RA continuum. It was present in 19% of the CCP-positive patients without clinical synovitis; 49% of the DMARD-naive early RA group; 57% of the late RA group; and in none of the healthy controls. Moreover, the number of inflamed interosseous tendons per patient also increased with RA progression.
A total of 12% of 507 nontender metacarpophalangeal joints showed MRI evidence of interosseous tendon inflammation, as did 28% of 141 tender ones (Ann Rheum Dis. 2019 Mar 23. doi: 10.1136/annrheumdis-2018-214331).
As part of the study, Dr. Emery and coinvestigators performed cadaveric dissections that demonstrated that the interosseous tendons don’t possess a tendon sheath and don’t directly communicate with the joint capsule.
A prospective study is warranted in order to confirm the observed association between interosseous tendon inflammation and clinical and subclinical synovitis and to establish the predictive value of hand MRI as a harbinger of RA, he noted.
Dr. Emery reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – Inflammation of the hand interosseous tendons found on MRI is a novel target in efforts to preempt the development and progression of rheumatoid arthritis, Paul Emery, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
He and his coinvestigators have previously shown there is a high prevalence of interosseous tendon inflammation in the hands of patients with established RA, but now they’ve demonstrated that this phenomenon also occurs in anti–cyclic citrullinated peptide (CCP)–positive individuals at increased risk for RA, even before onset of clinical synovitis.
This finding is consistent with the notion that, even though RA is classically considered a disease of the synovial joints, the joint involvement is a relatively late phenomenon in the disease development process and extracapsular structures may be important early targets of RA-related inflammation. Indeed, the MRI finding of tenosynovitis of the wrist and finger flexor tendons is known to be the strongest predictor of progression to arthritis in patients with recent-onset arthralgia or other musculoskeletal symptoms but no clinical synovitis, according to Dr. Emery, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Center.
Because the interosseous muscles of the hands play a critical role in hand function – pianists and other musicians not infrequently present to rheumatologists with overuse injuries of the muscles and their tendons – Dr. Emery and his coworkers decided to take a comprehensive look at interosseous tendon inflammation across the full spectrum of RA and pre-RA. They conducted a retrospective study of clinical and hand MRI data on 93 CCP-positive patients who presented with new-onset musculoskeletal symptoms but no clinical synovitis; 47 patients with early RA, all of whom were disease-modifying antirheumatic drug–naive; 28 patients with late RA as defined by at least 1 year of symptoms, anti-CCP and/or rheumatoid factor positivity, a Disease Activity Score in 28 joints (DAS28) of 3.2 or more, plus a history of exposure to one or more DMARDs at the time of their hand imaging; and 20 healthy controls.
The key finding is that the proportion of subjects with MRI evidence of interosseous tendon inflammation rose along the advancing RA continuum. It was present in 19% of the CCP-positive patients without clinical synovitis; 49% of the DMARD-naive early RA group; 57% of the late RA group; and in none of the healthy controls. Moreover, the number of inflamed interosseous tendons per patient also increased with RA progression.
A total of 12% of 507 nontender metacarpophalangeal joints showed MRI evidence of interosseous tendon inflammation, as did 28% of 141 tender ones (Ann Rheum Dis. 2019 Mar 23. doi: 10.1136/annrheumdis-2018-214331).
As part of the study, Dr. Emery and coinvestigators performed cadaveric dissections that demonstrated that the interosseous tendons don’t possess a tendon sheath and don’t directly communicate with the joint capsule.
A prospective study is warranted in order to confirm the observed association between interosseous tendon inflammation and clinical and subclinical synovitis and to establish the predictive value of hand MRI as a harbinger of RA, he noted.
Dr. Emery reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – Inflammation of the hand interosseous tendons found on MRI is a novel target in efforts to preempt the development and progression of rheumatoid arthritis, Paul Emery, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
He and his coinvestigators have previously shown there is a high prevalence of interosseous tendon inflammation in the hands of patients with established RA, but now they’ve demonstrated that this phenomenon also occurs in anti–cyclic citrullinated peptide (CCP)–positive individuals at increased risk for RA, even before onset of clinical synovitis.
This finding is consistent with the notion that, even though RA is classically considered a disease of the synovial joints, the joint involvement is a relatively late phenomenon in the disease development process and extracapsular structures may be important early targets of RA-related inflammation. Indeed, the MRI finding of tenosynovitis of the wrist and finger flexor tendons is known to be the strongest predictor of progression to arthritis in patients with recent-onset arthralgia or other musculoskeletal symptoms but no clinical synovitis, according to Dr. Emery, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Center.
Because the interosseous muscles of the hands play a critical role in hand function – pianists and other musicians not infrequently present to rheumatologists with overuse injuries of the muscles and their tendons – Dr. Emery and his coworkers decided to take a comprehensive look at interosseous tendon inflammation across the full spectrum of RA and pre-RA. They conducted a retrospective study of clinical and hand MRI data on 93 CCP-positive patients who presented with new-onset musculoskeletal symptoms but no clinical synovitis; 47 patients with early RA, all of whom were disease-modifying antirheumatic drug–naive; 28 patients with late RA as defined by at least 1 year of symptoms, anti-CCP and/or rheumatoid factor positivity, a Disease Activity Score in 28 joints (DAS28) of 3.2 or more, plus a history of exposure to one or more DMARDs at the time of their hand imaging; and 20 healthy controls.
The key finding is that the proportion of subjects with MRI evidence of interosseous tendon inflammation rose along the advancing RA continuum. It was present in 19% of the CCP-positive patients without clinical synovitis; 49% of the DMARD-naive early RA group; 57% of the late RA group; and in none of the healthy controls. Moreover, the number of inflamed interosseous tendons per patient also increased with RA progression.
A total of 12% of 507 nontender metacarpophalangeal joints showed MRI evidence of interosseous tendon inflammation, as did 28% of 141 tender ones (Ann Rheum Dis. 2019 Mar 23. doi: 10.1136/annrheumdis-2018-214331).
As part of the study, Dr. Emery and coinvestigators performed cadaveric dissections that demonstrated that the interosseous tendons don’t possess a tendon sheath and don’t directly communicate with the joint capsule.
A prospective study is warranted in order to confirm the observed association between interosseous tendon inflammation and clinical and subclinical synovitis and to establish the predictive value of hand MRI as a harbinger of RA, he noted.
Dr. Emery reported having no financial conflicts regarding his presentation.
REPORTING FROM RWCS 2019
Methotrexate pneumonitis called ‘super rare’
MAUI, HAWAII – The incidence of methotrexate pneumonitis has been reported as ranging from 3.5% to 7.6% among patients taking the disease-modifying antirheumatic drug. It’s an estimate that Aryeh Fischer, MD, counters with a one-word response: “Nonsense!”
“There’s just no way that methotrexate is causing that much lung disease,” he declared at the 2019 Rheumatology Winter Clinical Symposium.
Dr. Fischer, a rheumatologist with joint appointments to the divisions of rheumatology and pulmonary sciences and critical care medicine at the University of Colorado at Denver, Aurora, noted that his opinion is considered controversial in the pulmonology world.
“I’m not allowed to talk about methotrexate at lung conferences. They stop you at the gate. They’re convinced in lung circles that methotrexate is the worst drug known to mankind,” he said.
“My take home on methotrexate lung toxicity is this: I would just say, yes, it can occur, but it’s super rare and most often we’re not really sure that it was methotrexate pneumonitis. The diagnosis is not definitive, it’s exclusionary. We know that patients with interstitial lung disease of all types get acute exacerbations, and in idiopathic pulmonary fibrosis it’s actually the leading cause of mortality,” the rheumatologist said.
He highlighted a meta-analysis of 22 randomized, double-blind clinical trials published in 1990-2013 of methotrexate versus placebo or active comparators in 8,584 RA patients. The Irish investigators of that meta-analysis found that methotrexate was associated with a small albeit statistically significant 10% increase in the risk of all adverse respiratory events and an 11% increase in the risk of respiratory infection. However, patients on methotrexate were not at increased risk of mortality because of lung disease. And not a single case of methotrexate pneumonitis was reported after 2002 (Arthritis Rheumatol. 2014 Apr;66[4]:803-12).
Methotrexate pneumonitis is not dose dependent, nor is it related to treatment duration.
“Just because your patient has been on methotrexate for years does not mean they won’t get methotrexate lung toxicity,” he cautioned. “But this is not a chronic fibrotic interstitial lung disease, this is an acute onset of peripheral infiltrates and ground glass opacifications on chest imaging.”
Bronchoalveolar lavage classically shows a hypersensitivity pneumonitis with lymphocytosis. Transbronchial or surgical lung biopsy may show an organizing pneumonia or airway-based nonnecrotizing granulomas, again indicative of a hypersensitivity reaction.
Because the diagnostic picture is so often cloudy, Dr. Fischer generally tries to avoid methotrexate in patients with moderate or severe interstitial lung disease. “I have the luxury of avoiding it because we have so many great arthritis drugs these days,” he noted.
“That being said, the notion that we’re going to stop methotrexate in an 80-year-old who’s been on it for years and has mild bibasilar fibrotic interstitial lung disease so that her lung doc can sleep better at night is not very helpful for our patients. If the patient is doing well on methotrexate and the interstitial lung disease is mild, I continue [the methotrexate],” Dr. Fischer said.
He reported receiving research grants from Boehringer Ingelheim and Corbus Pharmaceuticals and serving as a consultant to Boehringer Ingelheim and other pharmaceutical companies.
MAUI, HAWAII – The incidence of methotrexate pneumonitis has been reported as ranging from 3.5% to 7.6% among patients taking the disease-modifying antirheumatic drug. It’s an estimate that Aryeh Fischer, MD, counters with a one-word response: “Nonsense!”
“There’s just no way that methotrexate is causing that much lung disease,” he declared at the 2019 Rheumatology Winter Clinical Symposium.
Dr. Fischer, a rheumatologist with joint appointments to the divisions of rheumatology and pulmonary sciences and critical care medicine at the University of Colorado at Denver, Aurora, noted that his opinion is considered controversial in the pulmonology world.
“I’m not allowed to talk about methotrexate at lung conferences. They stop you at the gate. They’re convinced in lung circles that methotrexate is the worst drug known to mankind,” he said.
“My take home on methotrexate lung toxicity is this: I would just say, yes, it can occur, but it’s super rare and most often we’re not really sure that it was methotrexate pneumonitis. The diagnosis is not definitive, it’s exclusionary. We know that patients with interstitial lung disease of all types get acute exacerbations, and in idiopathic pulmonary fibrosis it’s actually the leading cause of mortality,” the rheumatologist said.
He highlighted a meta-analysis of 22 randomized, double-blind clinical trials published in 1990-2013 of methotrexate versus placebo or active comparators in 8,584 RA patients. The Irish investigators of that meta-analysis found that methotrexate was associated with a small albeit statistically significant 10% increase in the risk of all adverse respiratory events and an 11% increase in the risk of respiratory infection. However, patients on methotrexate were not at increased risk of mortality because of lung disease. And not a single case of methotrexate pneumonitis was reported after 2002 (Arthritis Rheumatol. 2014 Apr;66[4]:803-12).
Methotrexate pneumonitis is not dose dependent, nor is it related to treatment duration.
“Just because your patient has been on methotrexate for years does not mean they won’t get methotrexate lung toxicity,” he cautioned. “But this is not a chronic fibrotic interstitial lung disease, this is an acute onset of peripheral infiltrates and ground glass opacifications on chest imaging.”
Bronchoalveolar lavage classically shows a hypersensitivity pneumonitis with lymphocytosis. Transbronchial or surgical lung biopsy may show an organizing pneumonia or airway-based nonnecrotizing granulomas, again indicative of a hypersensitivity reaction.
Because the diagnostic picture is so often cloudy, Dr. Fischer generally tries to avoid methotrexate in patients with moderate or severe interstitial lung disease. “I have the luxury of avoiding it because we have so many great arthritis drugs these days,” he noted.
“That being said, the notion that we’re going to stop methotrexate in an 80-year-old who’s been on it for years and has mild bibasilar fibrotic interstitial lung disease so that her lung doc can sleep better at night is not very helpful for our patients. If the patient is doing well on methotrexate and the interstitial lung disease is mild, I continue [the methotrexate],” Dr. Fischer said.
He reported receiving research grants from Boehringer Ingelheim and Corbus Pharmaceuticals and serving as a consultant to Boehringer Ingelheim and other pharmaceutical companies.
MAUI, HAWAII – The incidence of methotrexate pneumonitis has been reported as ranging from 3.5% to 7.6% among patients taking the disease-modifying antirheumatic drug. It’s an estimate that Aryeh Fischer, MD, counters with a one-word response: “Nonsense!”
“There’s just no way that methotrexate is causing that much lung disease,” he declared at the 2019 Rheumatology Winter Clinical Symposium.
Dr. Fischer, a rheumatologist with joint appointments to the divisions of rheumatology and pulmonary sciences and critical care medicine at the University of Colorado at Denver, Aurora, noted that his opinion is considered controversial in the pulmonology world.
“I’m not allowed to talk about methotrexate at lung conferences. They stop you at the gate. They’re convinced in lung circles that methotrexate is the worst drug known to mankind,” he said.
“My take home on methotrexate lung toxicity is this: I would just say, yes, it can occur, but it’s super rare and most often we’re not really sure that it was methotrexate pneumonitis. The diagnosis is not definitive, it’s exclusionary. We know that patients with interstitial lung disease of all types get acute exacerbations, and in idiopathic pulmonary fibrosis it’s actually the leading cause of mortality,” the rheumatologist said.
He highlighted a meta-analysis of 22 randomized, double-blind clinical trials published in 1990-2013 of methotrexate versus placebo or active comparators in 8,584 RA patients. The Irish investigators of that meta-analysis found that methotrexate was associated with a small albeit statistically significant 10% increase in the risk of all adverse respiratory events and an 11% increase in the risk of respiratory infection. However, patients on methotrexate were not at increased risk of mortality because of lung disease. And not a single case of methotrexate pneumonitis was reported after 2002 (Arthritis Rheumatol. 2014 Apr;66[4]:803-12).
Methotrexate pneumonitis is not dose dependent, nor is it related to treatment duration.
“Just because your patient has been on methotrexate for years does not mean they won’t get methotrexate lung toxicity,” he cautioned. “But this is not a chronic fibrotic interstitial lung disease, this is an acute onset of peripheral infiltrates and ground glass opacifications on chest imaging.”
Bronchoalveolar lavage classically shows a hypersensitivity pneumonitis with lymphocytosis. Transbronchial or surgical lung biopsy may show an organizing pneumonia or airway-based nonnecrotizing granulomas, again indicative of a hypersensitivity reaction.
Because the diagnostic picture is so often cloudy, Dr. Fischer generally tries to avoid methotrexate in patients with moderate or severe interstitial lung disease. “I have the luxury of avoiding it because we have so many great arthritis drugs these days,” he noted.
“That being said, the notion that we’re going to stop methotrexate in an 80-year-old who’s been on it for years and has mild bibasilar fibrotic interstitial lung disease so that her lung doc can sleep better at night is not very helpful for our patients. If the patient is doing well on methotrexate and the interstitial lung disease is mild, I continue [the methotrexate],” Dr. Fischer said.
He reported receiving research grants from Boehringer Ingelheim and Corbus Pharmaceuticals and serving as a consultant to Boehringer Ingelheim and other pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2019
Lymphoma rate in RA patients is falling
MAUI, HAWAII – The incidence of lymphoma in patients with RA appears to have been dropping during the past 2 decades – and for rheumatologists, that’s news you can use.
“I think this is encouraging data about where we’re headed with therapy. And it’s encouraging data for your patients, that maybe more effective therapies can lead to a lower risk of cancer,” John J. Cush, MD, commented at the 2019 Rheumatology Winter Clinical Symposium.
“Patients are always worried about cancer,” observed symposium director Arthur Kavanaugh, MD. “I think this is very useful data to bring to a discussion with patients.”
The study they highlighted was presented at the 2018 annual meeting of the American College of Rheumatology by Namrata Singh, MD, of the University of Iowa, Iowa City and coinvestigators from Veterans Affairs medical centers around the country. They analyzed the incidence of lymphomas as well as all-site cancers in 50,870 men with RA in the national VA health care system during 2001-2015 and compared the rates with the background rates in the general U.S. population as captured in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program.
The key finding: While the standardized incidence ratio for the development of lymphoma in the RA patients during 2001-2005 was 190% greater than in the SEER population, the SIR dropped to 1.6 in 2006-2010 and stayed low in 2011-2015.
“These are the only data I’m aware of that say maybe lymphomas are becoming less frequent among RA patients,” said Dr. Kavanaugh, professor of medicine at the University of California, San Diego.
Historically, RA has been associated with roughly a 100% increased risk of lymphoma. The source of the increased risk has been a matter of controversy: Is it the result of immunostimulation triggered by high RA disease activity, or a side effect of the drugs employed in treatment of the disease? The clear implication of the VA study is that it’s all about disease activity.
“The lymphoma rate is higher early in the use of our new therapies, in 2001-2005, because the patients who went on TNF [tumor necrosis factor] inhibitors then had the most disease activity. But with time, patients are getting those treatments earlier. Does this [lower lymphoma rate] reflect a change in the practice of rheumatology? I think it does,” according to Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas.
Dr. Kavanaugh agreed. “Now, if we’re treating early and treating to target, we should see less lymphomas than we did back in the day.”
The rate of cancers at all sites in the VA RA patients has been going down as well, with the SIR dropping from 1.8 in 2001-2005 to close to 1, the background rate in the general population.
“What’s great about this study is this is a large data set. You really can’t compare an RA population on and off treatment. The right comparison is to a normal population – and SEER accounts for something like 14% of the U.S. population,” Dr. Cush said.
Previous support for the notion that the increased lymphoma risk associated with RA was a function of disease activity came from a Swedish study of 378 RA patients in the prebiologic era who developed lymphoma and a matched cohort of 378 others without lymphoma. The investigators found that patients with moderate overall RA disease activity were at a 700% increased risk of lymphoma, compared with those with low overall disease activity, and that patients with high RA disease activity were at a 6,900% increased risk (Arthritis Rheum. 2006 Mar;54[3]:692-701). But that was a cross-sectional study, whereas the VA study examined trends over time.
The VA RA cohort had a mean age of 64 years. About 60% were current or ex-smokers, 65% were positive for rheumatoid factor, and 62% were positive for anticyclic citrullinated peptide.
Dr. Kavanaugh said that, because of the potential for referral bias in the VA study, he’s eager to see the findings reproduced in another data set.
Both Dr. Cush and Dr. Kavanaugh reported serving as a consultant to and/or receiving research funding from numerous pharmaceutical companies.
MAUI, HAWAII – The incidence of lymphoma in patients with RA appears to have been dropping during the past 2 decades – and for rheumatologists, that’s news you can use.
“I think this is encouraging data about where we’re headed with therapy. And it’s encouraging data for your patients, that maybe more effective therapies can lead to a lower risk of cancer,” John J. Cush, MD, commented at the 2019 Rheumatology Winter Clinical Symposium.
“Patients are always worried about cancer,” observed symposium director Arthur Kavanaugh, MD. “I think this is very useful data to bring to a discussion with patients.”
The study they highlighted was presented at the 2018 annual meeting of the American College of Rheumatology by Namrata Singh, MD, of the University of Iowa, Iowa City and coinvestigators from Veterans Affairs medical centers around the country. They analyzed the incidence of lymphomas as well as all-site cancers in 50,870 men with RA in the national VA health care system during 2001-2015 and compared the rates with the background rates in the general U.S. population as captured in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program.
The key finding: While the standardized incidence ratio for the development of lymphoma in the RA patients during 2001-2005 was 190% greater than in the SEER population, the SIR dropped to 1.6 in 2006-2010 and stayed low in 2011-2015.
“These are the only data I’m aware of that say maybe lymphomas are becoming less frequent among RA patients,” said Dr. Kavanaugh, professor of medicine at the University of California, San Diego.
Historically, RA has been associated with roughly a 100% increased risk of lymphoma. The source of the increased risk has been a matter of controversy: Is it the result of immunostimulation triggered by high RA disease activity, or a side effect of the drugs employed in treatment of the disease? The clear implication of the VA study is that it’s all about disease activity.
“The lymphoma rate is higher early in the use of our new therapies, in 2001-2005, because the patients who went on TNF [tumor necrosis factor] inhibitors then had the most disease activity. But with time, patients are getting those treatments earlier. Does this [lower lymphoma rate] reflect a change in the practice of rheumatology? I think it does,” according to Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas.
Dr. Kavanaugh agreed. “Now, if we’re treating early and treating to target, we should see less lymphomas than we did back in the day.”
The rate of cancers at all sites in the VA RA patients has been going down as well, with the SIR dropping from 1.8 in 2001-2005 to close to 1, the background rate in the general population.
“What’s great about this study is this is a large data set. You really can’t compare an RA population on and off treatment. The right comparison is to a normal population – and SEER accounts for something like 14% of the U.S. population,” Dr. Cush said.
Previous support for the notion that the increased lymphoma risk associated with RA was a function of disease activity came from a Swedish study of 378 RA patients in the prebiologic era who developed lymphoma and a matched cohort of 378 others without lymphoma. The investigators found that patients with moderate overall RA disease activity were at a 700% increased risk of lymphoma, compared with those with low overall disease activity, and that patients with high RA disease activity were at a 6,900% increased risk (Arthritis Rheum. 2006 Mar;54[3]:692-701). But that was a cross-sectional study, whereas the VA study examined trends over time.
The VA RA cohort had a mean age of 64 years. About 60% were current or ex-smokers, 65% were positive for rheumatoid factor, and 62% were positive for anticyclic citrullinated peptide.
Dr. Kavanaugh said that, because of the potential for referral bias in the VA study, he’s eager to see the findings reproduced in another data set.
Both Dr. Cush and Dr. Kavanaugh reported serving as a consultant to and/or receiving research funding from numerous pharmaceutical companies.
MAUI, HAWAII – The incidence of lymphoma in patients with RA appears to have been dropping during the past 2 decades – and for rheumatologists, that’s news you can use.
“I think this is encouraging data about where we’re headed with therapy. And it’s encouraging data for your patients, that maybe more effective therapies can lead to a lower risk of cancer,” John J. Cush, MD, commented at the 2019 Rheumatology Winter Clinical Symposium.
“Patients are always worried about cancer,” observed symposium director Arthur Kavanaugh, MD. “I think this is very useful data to bring to a discussion with patients.”
The study they highlighted was presented at the 2018 annual meeting of the American College of Rheumatology by Namrata Singh, MD, of the University of Iowa, Iowa City and coinvestigators from Veterans Affairs medical centers around the country. They analyzed the incidence of lymphomas as well as all-site cancers in 50,870 men with RA in the national VA health care system during 2001-2015 and compared the rates with the background rates in the general U.S. population as captured in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program.
The key finding: While the standardized incidence ratio for the development of lymphoma in the RA patients during 2001-2005 was 190% greater than in the SEER population, the SIR dropped to 1.6 in 2006-2010 and stayed low in 2011-2015.
“These are the only data I’m aware of that say maybe lymphomas are becoming less frequent among RA patients,” said Dr. Kavanaugh, professor of medicine at the University of California, San Diego.
Historically, RA has been associated with roughly a 100% increased risk of lymphoma. The source of the increased risk has been a matter of controversy: Is it the result of immunostimulation triggered by high RA disease activity, or a side effect of the drugs employed in treatment of the disease? The clear implication of the VA study is that it’s all about disease activity.
“The lymphoma rate is higher early in the use of our new therapies, in 2001-2005, because the patients who went on TNF [tumor necrosis factor] inhibitors then had the most disease activity. But with time, patients are getting those treatments earlier. Does this [lower lymphoma rate] reflect a change in the practice of rheumatology? I think it does,” according to Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas.
Dr. Kavanaugh agreed. “Now, if we’re treating early and treating to target, we should see less lymphomas than we did back in the day.”
The rate of cancers at all sites in the VA RA patients has been going down as well, with the SIR dropping from 1.8 in 2001-2005 to close to 1, the background rate in the general population.
“What’s great about this study is this is a large data set. You really can’t compare an RA population on and off treatment. The right comparison is to a normal population – and SEER accounts for something like 14% of the U.S. population,” Dr. Cush said.
Previous support for the notion that the increased lymphoma risk associated with RA was a function of disease activity came from a Swedish study of 378 RA patients in the prebiologic era who developed lymphoma and a matched cohort of 378 others without lymphoma. The investigators found that patients with moderate overall RA disease activity were at a 700% increased risk of lymphoma, compared with those with low overall disease activity, and that patients with high RA disease activity were at a 6,900% increased risk (Arthritis Rheum. 2006 Mar;54[3]:692-701). But that was a cross-sectional study, whereas the VA study examined trends over time.
The VA RA cohort had a mean age of 64 years. About 60% were current or ex-smokers, 65% were positive for rheumatoid factor, and 62% were positive for anticyclic citrullinated peptide.
Dr. Kavanaugh said that, because of the potential for referral bias in the VA study, he’s eager to see the findings reproduced in another data set.
Both Dr. Cush and Dr. Kavanaugh reported serving as a consultant to and/or receiving research funding from numerous pharmaceutical companies.
REPORTING FROM RWCS 2019
FDA approves new etanercept biosimilar, Eticovo
The Food and Drug Administration has approved Eticovo (etanercept-ykro), a biosimilar of Enbrel (etanercept), for the treatment of several different rheumatologic and dermatologic conditions.
FDA approval was based in part on the results of a phase 3 trial in which 596 patients with moderate to severe rheumatoid arthritis uncontrolled by methotrexate received either Eticovo or Enbrel. The American College of Rheumatology 20% response rate after 24 weeks was 78.1% for Eticovo and 80.3% for Enbrel; the two drugs were statistically equivalent. Both groups had statistically equivalent rates of treatment-emergent adverse events (55.2% vs. 58.2%).
According to the label, Eticovo is a tumor necrosis factor blocker approved for the treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis in patients aged 4 years or older. The most common adverse events associated with the drug include infections and injection site reactions.
Eticovo is the second etanercept biosimilar approved by the FDA. The first FDA-approved etanercept biosimilar, etanercept-szzs (Erelzi), is currently facing a legal challenge from Amgen, the manufacturer of Enbrel.
The Food and Drug Administration has approved Eticovo (etanercept-ykro), a biosimilar of Enbrel (etanercept), for the treatment of several different rheumatologic and dermatologic conditions.
FDA approval was based in part on the results of a phase 3 trial in which 596 patients with moderate to severe rheumatoid arthritis uncontrolled by methotrexate received either Eticovo or Enbrel. The American College of Rheumatology 20% response rate after 24 weeks was 78.1% for Eticovo and 80.3% for Enbrel; the two drugs were statistically equivalent. Both groups had statistically equivalent rates of treatment-emergent adverse events (55.2% vs. 58.2%).
According to the label, Eticovo is a tumor necrosis factor blocker approved for the treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis in patients aged 4 years or older. The most common adverse events associated with the drug include infections and injection site reactions.
Eticovo is the second etanercept biosimilar approved by the FDA. The first FDA-approved etanercept biosimilar, etanercept-szzs (Erelzi), is currently facing a legal challenge from Amgen, the manufacturer of Enbrel.
The Food and Drug Administration has approved Eticovo (etanercept-ykro), a biosimilar of Enbrel (etanercept), for the treatment of several different rheumatologic and dermatologic conditions.
FDA approval was based in part on the results of a phase 3 trial in which 596 patients with moderate to severe rheumatoid arthritis uncontrolled by methotrexate received either Eticovo or Enbrel. The American College of Rheumatology 20% response rate after 24 weeks was 78.1% for Eticovo and 80.3% for Enbrel; the two drugs were statistically equivalent. Both groups had statistically equivalent rates of treatment-emergent adverse events (55.2% vs. 58.2%).
According to the label, Eticovo is a tumor necrosis factor blocker approved for the treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis in patients aged 4 years or older. The most common adverse events associated with the drug include infections and injection site reactions.
Eticovo is the second etanercept biosimilar approved by the FDA. The first FDA-approved etanercept biosimilar, etanercept-szzs (Erelzi), is currently facing a legal challenge from Amgen, the manufacturer of Enbrel.