TNF-α Antagonist Use in Autoimmune Diseases

Tumor necrosis factor (TNF)-α antagonists have proven successful in the treatment of autoimmune diseases; however, there have been concerns about the safety of these biologic drugs. New research found that the overall initiation of TNF-α antagonists was not associated with increased risk of hospitalization for serious infections compared with treatment using nonbiologic regimens [JAMA. 2011;306(21):2331-2339]. As part of a US multi-institutional initiative, the Safety Assessment of Biologic Therapy project, researchers from Vanderbilt University evaluated whether initiation of TNF-α antagonists was linked with an increased risk of serious infections among patients with autoimmune diseases, and whether risk varies by specific TNF-α antagonist. 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) combining data from 4 large US automated databases. For each database, the investigators identified patients with study-defined autoimmune diseases who subsequently filled a prescription or received an infusion for a TNF-α antagonist or comparator medication. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score–matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate. Study medications were classified into 2 groups: TNF-α antagonists (including infliximab, adalimumab, and etanercept) and comparator medications. For RA, the comparator therapies were initiation of leflunomide, sulfasalazine, or hydroxychloroquine after use of methotrexate in the previous year. For IBD, the comparator group was initiation of azathioprine or mercaptopurine. For psoriasis and spondyloarthropathies, the comparator group was initiation of methotrexate, hydroxychloroquine, sulfasalazine, or leflunomide. The primary outcome measure was serious infections requiring hospitalization during the first 12 months following initiation of TNF-α antagonists or nonbiologic regimens. Study cohorts included 10,484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Patients with >1 autoimmune disease were excluded. For RA patients, initiating TNF-α antagonists and comparator medications had similar baseline characteristics. The mean age was 58 years, 87% were women, and 61% were Caucasian. Of patients initiating TNF-α antagonists, 70% had used methotrexate during baseline. Similarly, after propensity score-matching, there was no significant difference in the distribution of covariates between exposure for the IBD and psoriasis and spondyloarthropathies groups. This study identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. For RA patients, the hospitalization rate for serious infections in the TNF-α antagonist group (8.16) did not differ significantly from the rate for the comparator regimens (7.78) per 100 person-years (adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 0.91-1.21). Baseline glucocorticoid use, however, was associated with a dose-dependent increase in infections. For RA patients taking infliximab, a higher rate of serious infections was observed compared with etanercept and adalimumab (aHR, 1.25; 95% CI, 1.07-1.48 vs aHR, 1.26; 95% CI, 1.07-1.77 and aHR 1.23; 95% CI, 1.02-1.48, respectively). Among patients with IBD, initiating TNF-α antagonist regimens was not significantly higher than with patients taking azathioprine or mercaptopurine (10.91 vs 9.60, respectively) per 100 person-years (aHR, 1.10; 95% CI, 0.83-1.46). The rate of serious infections in the psoriasis and spondyloarthropathies cohort was slightly higher for those taking TNF-α antagonists than the comparator regimens (5.41 vs 5.37, respectively) per 100 person-years (aHR, 1.05; 95% CI, 0.76-1.45). Study limitations noted by the authors included that the researchers relied on coded information from administrative claims and other data not directly culled for clinical care to identify study outcomes. This study also had insufficient numbers to evaluate the role of specific TNF-α antagonists on serious infections for IBD and psoriasis and spondyloarthropathies. In summary, the researchers concluded that they observed higher absolute rates of infections compared with previously published cohort studies and randomized controlled trials. However, there was 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.