Infection Risk with Anti-TNF Therapy
The advent of tumor necrosis factor-α (TNF-α) antagonists has been lifesaving and lifestyle-saving for many people with rheumatoid arthritis (RA). The use of these biologic drugs is now expanding to treat other diseases, including inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, and juvenile arthritis.
What Problem Was Studied?
People with serious inflammatory diseases, like RA, often get infections. These infections may be related either to the underlying disease or to medications taken as treatment. Several recent studies examining the effect of TNF-α antagonist therapy on infection risk have yielded conflicting results. To address the uncertainties of the risk of infection, a team of scientists from the University of Alabama at Birmingham and the Center for Health Care Policy and Evaluation in Eden Prairie, Minn., conducted a study of people with RA enrolled in a large health care organization. They sought to compare the infection rates of those who received methotrexate (a non-biologic disease-modifying antirheumatic drug) versus those who received anti-TNF therapy.
What Was Done in the Study?
Partially supported by a grant from the Maryland Chapter of the Arthritis Foundation, senior investigator Kenneth G. Saag, MD, MSc, and team used the medical and pharmacy claim forms of the health care organization to identify adults with RA. They identified individuals who had received an infusion or filled a prescription for a TNF-α antagonist or filled at least three prescriptions for methotrexate. From that group, they selected those who had hospitalizations with diagnostic codes for bacterial infections. They required that hospitalizations occurred within six months of the most recent dose of medication.
What Were the Study Results?
Jeffrey R. Curtis, MD, MPH, lead author of the published study, attended the 2007 Arthritis Research Conference hosted by the Arthritis Foundation and presented the results. Of the thousands of people identified who had received anti–TNF-α therapy or methotrexate, 217 serious bacterial infections were identified. Of those 217, medical records were obtained for 187. Of the 2,393 individuals exposed to TNF-α antagonists, 2.7% contracted a serious infection. Of the 2,933 people who took methotrexate but no anti–TNF-α, 2.0% contracted a serious infection. After adjusting for demographic factors, RA severity, cormorbid medical conditions and prednisone use, there was an almost two-fold increased risk of hospitalization with a bacterial infection among those who received anti-TNF therapy. The majority of infections were pneumonias and occurred within 90 days of exposure to the biologic.
What Does This Mean For People With RA?
Dr. Curtis says “The dramatic efficacy of TNF-α antagonist therapy for most RA patients needs to be balanced against the potential harm of an increased risk of infection associated with these agents, albeit with the recognition that the absolute difference in the number of infections was relatively low (0.7 infections per 100 patients).” He goes on to recommend that people taking these medications, and their physicians, should vigilantly monitor for signs of infection, particularly shortly after treatment initiation.
Curtis JR, Patkar N, Xie A, et al. Risk of serious bacterial infections among rheumatoid arthritis patients exposed to tumor necrosis factor a antagonists. Arthritis Rheum 2007;56:1125-33.
|News of Note from Arthritis Research Conference |
Along with Dr. Curtis, two other Foundation-funded researchers presented their work during the Clinical Outcomes session. Esi Morgan DeWitt, MD, MSCE (Duke Clinical Research Institute, Durham), discussed research in the area of patient access to biologic therapeutics. She presented results from the study of a database in which biologic use was associated with younger patient age, higher income, and higher disability scores compared to non-biologic DMARD use.
Soko Setoguchi, MD, DrPH (Brigham and Women’s Hospital and Harvard Medical School, Boston), next presented results of a study conducted on the safety of TNF-a antagonists for rheumatoid arthritis with respect to cancer using large pooled administrative databases. The study reported a low likelihood of an increased risk of cancer with biologics compared to methotrexate use.