Newswise — When compared to methotrexate and other disease-modifying antirheumatic drugs, anti-TNF and biologic therapy does not significantly increase the risk of infection in people with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Philadelphia, Pa.
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.
TNF-antagonists (anti-TNF therapy; among drugs called biologics) are a class of drugs that have been used since 1998; overall, they have been given to more than 600,000 people worldwide. These drugs are given to lessen inflammation by interfering with biologic substances that cause or worsen inflammation. Their use is associated with an increased risk of certain types of infections, including tuberculosis, but it has been uncertain whether their use increases the overall risk of infection in patients with rheumatoid arthritis compared to non-biologic treatments.
Researchers recently compared the risk of infection associated with biologic therapies to that of DMARDs alone by looking at information contained in the Consortium of Rheumatology Researchers of North America registry. They reviewed information on 18,305 people with RA – considering disease activity, their ability to function, the duration of the disease, prior prednisone use, and whether or not the patients had diabetes or lung disease—and requested the medical records of any patient who reported a hospitalization with infection.
Among the 18,305 patients who were identified, 586 hospitalized infections (of which 91 percent were confirmed via hospital records) and 21,258 outpatient infections were reported. Researchers found that the overall risk of serious infection was not increased with anti-TNF therapy when compared to DMARDs. Other biologics such as anakinra (Kineret®), abatacept (ORENCIA®), and rituximab (Rituxan®) were likewise not associated with an increased risk for infection after controlling for a number of factors that were associated with infections. Non-medication related factors associated with infections included age, RA clinical disease activity index, measures of physical function, duration of RA, lung disease, prior infection, prednisone dose, and the number of previous DMARDs taken.
“The most important risk factors for serious infections were not biologic medications, as some might have expected, but instead were age, medical conditions such as emphysema, and RA-specific factors like disease duration,” explains Jeffrey R. Curtis, MD MPH; director, Arthritis Clinical Intervention Program; division of clinical immunology and rheumatology, University of Alabama at Birmingham, Birmingham, Ala., and lead investigator in the study. “Although some of these might not be modifiable by patients or doctors, prednisone use and dose may be.”
Patients should talk to their rheumatologists to determine their best course of treatment.
The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see www.rheumatology.org/annual.
Editor’s Notes: Dr. Curtis will present this research during the ACR Annual Scientific Meeting at the Pennsylvania Convention Center at 11:30 AM on Wednesday, October 21in Room 108 B. Dr. Curtis will be available for media questions and briefing at 8:30 AM on Sunday, October 18 in the on-site press conference room, 109 A.
Presentation Number: 2059
The Risk for Hospitalized and Outpatient Infections Related to Anti-TNF Therapy and Newer Biologics
Jeffrey R. Curtis, MD, UAB, Birmingham, AL Lang Chen, MD, PhD, UAB, Birmingham, AL John J. Cush, MD, Baylor Research Institute, Dallas, TX Kathryn H. Dao, MD, Texas Health, Dallas, TX Elizabeth Delzell, ScD, Department of Epidemiology, UAB, Birmingham, AL D. E. Furst, M, Rheumatology, UCLA, Los Angeles, CA J. Greenberg, MD, MPH, NYU, New York, NY Marc C. Hochberg, MD, MPH, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD Archana Jain, MD, UAB, Birmingham, AL Joel M. Kremer, MD, Albany Medical College, Albany, NY Nivedita Patkar, MD, Immunology/Rheumatology, UAB, Birmingham, AL Daniel H. Solomon, MD, MPH, Brigham & Women's Hospital, Boston, MA
Purpose: There have been inconsistent results regarding the association between anti-TNF therapies and the risk of serious infection. Several prior studies had relatively poor adjustment for RA disease severity, while other analyses may have had biased ascertainment of infectious outcomes. We compared the risk of infection associated with anti-TNF therapies and other biologics to non-biologic DMARDs in a cohort with substantial information about disease severity.
Method: Data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry was used to identify a cohort of rheumatoid arthritis (RA) patients, RA disease factors, and their relevant DMARD exposures. For patients with reported hospitalized infections, medical records were requested. Cox proportional hazards models estimated the risk for hospitalized infections associated with current use of various biologic DMARDs compared to non-biologic DMARDs. Disease activity (CDAI), functional status (mHAQ), duration of RA, diabetes, lung disease, prior infection, prednisone dose, and number of previous infections were included in adjusted analyses. Sensitivity analysis considered how recently each of the drugs was initiated (< 1 year, ≥ 1 year), and also restricted eligible participants to new users of various medications. Additional analyses using Poisson regression evaluated the risk for all infections (hospitalized and outpatient).
Results: Among 18,305 RA patients with 32,911 years of observation, 586 hospitalized infections and 21,258 outpatient infections were reported. A total of 91% of the hospitalized infections had hospital record evidence to confirm the event; the remaining 9% were not counted as cases. In adjusted analyses, no significant increase in serious infection risk associated was observed for anti-TNF therapy or other biologics compared to non-biologic DMARDs. Factors that were associated with infections included age, RA clinical disease activity index (CDAI), mHAQ, duration of RA, lung disease, prior infection, prednisone dose, and number of previous non-biologic DMARDs. Consistent with the hospitalized infection results, there was no significant difference in the rate associated with the various biologics for the endpoint of all infections.
Conclusion: In an observational cohort of RA patients, we found no significant increase in the adjusted risk for hospitalized or outpatient infections associated with anti-TNF therapy or other biologics compared to MTX and other non-biologic DMARDs. The infection-related safety profiles of the various biologic agents appear to be similar.
Disclosure: J. R. Curtis, Roche Pharmaceuticals, 5, UCB, 5, Proctor & Gamble Pharmaceuticals, 5, Amgen, 5, Centocor, Inc., 5, Corrona, 5, Novartis Pharmaceutical Corporation, 2, Amgen, 2, Merck Pharmaceuticals, 2, Eli Lilly, 2, Proctor & Gamble Pharmaceuticals, 2, Roche Pharmaceuticals, 2, Centocor, Inc., 2, Corrona, 2, Novartis Pharmaceutical Corporation, 8, Proctor & Gamble Pharmaceuticals, 8, Eli Lilly and Company, 8, Roche Pharmaceuticals, 8, Merck Pharmaceuticals, 8 ; L. Chen, None; J. J. Cush, Centocor, Inc., 2, Celegene, 2, Roche, 2, Genentech, 5, Pfizer Inc, 2, UCB, 5, Abbott Laboratories, 2, Centocor, 5, Amgen, 5, UCB, 2, Genentech , 2 ; K. H. Dao, None; E. Delzell, Amgen, Inc, 2 ; D. E. Furst, None; J. Greenberg, Corrona, 5, Centocor, Inc., 5, Bristol-Myers Squibb, 2, Genentech and Biogen IDEC Inc., 5, Roche Pharmaceuticals, 5 ; M. C. Hochberg, None; A. Jain, None; J. M. Kremer, Abbott Immunology Pharmaceuticals, Amgen, Centocor, BMS, 2, Abbott, Amgen, Centocor, BMS, 5 ; N. Patkar, None; D. H. Solomon, Amgen, 2, Abbott Immunology Pharmaceuticals, 2 .
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