The study is being released early online to coincide with its presentation at the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Scientific Meeting.

Even though the introduction of medications known as tumor necrosis factor (TNF)-α antagonists have revolutionized the treatment of autoimmune diseases, concerns about their safety have remained. "Several studies reported serious infections in users of TNF-α antagonists. However, whether the risk of serious infections with TNF-α antagonists is greater than that with comparator nonbiologic medications is unclear," according to background information in the article.

Carlos G. Grijalva, M.D., M.P.H., of Vanderbilt University, Nashville, Tenn., and colleagues evaluated whether initiation of TNF-α antagonists was associated with an increased risk of serious infections among patients with autoimmune diseases, and whether risk varies by specific TNF-α antagonist. Within a U.S. multi-institutional collaboration (the SABER project), the researchers assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies [disease of the joints of the spine]), and compared the use and outcomes of TNF-α antagonists and nonbiologic regimens. Baseline glucocorticoid use was evaluated as a separate covariate. The primary outcome the researchers measured was infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens.

The study cohorts included 10,484 RA, 2,323 IBD, and 3,215 psoriasis and spondyloarthropathies matched pairs of patients using TNF-α antagonists and comparator medications. Overall, the researchers identified 1,172 serious infections, most of which (53 percent) were pneumonia and skin and soft tissue infections. The case fatality rate during hospitalizations for serious infections was 3.6 percent (30/823) for RA, 2.1 percent (4/194) for IBD, and 7.1 percent (11/155) for psoriasis.

An analyses of the data indicated that serious infection hospitalization rates were not significantly different between the TNF-α antagonists overall and the comparator regimens for RA, IBD and psoriasis, psoriatic arthritis, or ankylosing spondylitis. The authors did find that among patients with RA, the medication infliximab was associated with a significant increase in serious infections compared with the drugs etanercept and adalimumab. Baseline glucocorticoid use was associated with a dose-dependent increase in infections.

"In conclusion, in this large retrospective cohort study of predominantly low-income and vulnerable U.S. patients with autoimmune diseases, we observed higher absolute rates of infection compared with previously published cohort studies and randomized controlled trials. We found no increased risk of hospitalizations for serious infections among patients initiating a TNF-α antagonist (as a group) compared with those taking comparator nonbiologic therapies," the authors write.

Editorial: Is Anti-TNF Therapy Safer Than Previously Thought?

Will Dixon, M.R.C.P., Ph.D., of the University of Manchester, England, and David T. Felson, M.D., M.P.H., of the Boston University School of Medicine, comment on the findings of this study in an accompanying editorial.

"Given its large and comprehensive information about drug use and outcomes, the SABER project will certainly contribute to the understanding of the risks of biologic therapy. Conflicting findings between large pharmacoepidemiology studies are to be expected, and exploring reasons for discrepant results can yield helpful insights. From existing knowledge plus this recent study by Grijalva et al, one conclusion is that when compared with ongoing nonbiologic disease-modifying antirheumatic drug (DMARD) use, infection rates are increased in patients who started treatment with anti-TNF agents. However, this study suggests that serious infection risk may be no higher in those initiating anti-TNF therapy than in those starting a new DMARD, perhaps in combination with methotrexate. These intriguing findings need replication in other studies. Nevertheless, the report by Grijalva et al raises important questions about the comparative safety of immunosuppressant and biologic therapy and may prompt a re-evaluation of anti-TNF safety."

Note: If no author is given, the source is cited instead.

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