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Original Contribution
December 7, 2011

Initiation of Tumor Necrosis Factor-α Antagonists and the Risk of Hospitalization for Infection in Patients With Autoimmune Diseases

Author Affiliations

Author Affiliations: Department of Preventive Medicine, Vanderbilt University, Nashville, Tennessee (Drs Grijalva and Griffin); University of Alabama at Birmingham (Drs Chen, Delzell, Baddley, Beukelman, Patkar, Saag, and Curtis and Ms Xie); Birmingham VA Medical Center (Drs Baddley); Oregon Health & Science University, Portland (Dr Winthrop); Kaiser Permanente Northern California, Oakland (Drs Herrinton and Liu); Food and Drug Administration, Silver Spring, Maryland (Dr Ouellet-Hellstrom); Brigham and Women's Hospital and Harvard University, Boston, Massachusetts (Dr Solomon); and Center for Clinical Epidemiology and Biostatistics, Departments of Medicine and Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia (Dr Lewis).

JAMA. 2011;306(21):2331-2339. doi:10.1001/jama.2011.1692

Context Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete.

Objectives To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization.

Design, Setting, and Patients Within a US multi-institutional collaboration, we 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) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)–matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate.

Main Outcome Measure Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens.

Results Study cohorts included 10 484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections.

Conclusion Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.