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

Abstract

Context Although tumor necrosis factor alpha (TNF-α) antagonists are increasingly used in place of non-biologic comparator medications, their safety profile remains incomplete. Objectives To determine whether initiation of TNF-α antagonists compared with non-biologic comparators is associated with an increased risk of serious infections. 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 (PsO-PsA-AS) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid and National Medicaid/Medicare. TNF-α antagonists and non-biologic regimens were compared in disease specific-propensity score (PS) matched cohorts using Cox regression models with non-biologics as 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 non-biologic regimens. Results Study cohorts included 10484 RA, 2323 IBD and 3213 PsO-PsA-AS PS-matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1171 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among RA patients, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR]: 1.07 (95% CI: 0.93–1.23)). Among IBD patients, rates were 10.91 and 9.60 per 100 person-years (aHR: 1.13, (0.85–1.50)). Among PsO-PsA-AS patients, rates were 5.41 and 5.19 per 100 person-years (aHR: 1.10, (0.80–1.53)). Among RA patients, infliximab was associated with a significant increase in serious infections compared with etanercept and adalimumab (aHRs: 1.27 (1.08–1.49) and 1.23 (1.02–1.48)). Baseline glucocorticoid use was associated with a dose-dependent increase in infections. Conclusions Among patients with autoimmune diseases, compared to treatment with non-biologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.

Detection of Legionella pneumophila serogroup 1 in blood cultures from a patient treated with tumor necrosis factor-alpha inhibitor

“…Recently, some reports have described LD in patients receiving TNF-α inhibitors [22][23][24] and the relative risk for LD in patients treated with TNF-α inhibitor was between 16.5 and 21 compared to that for the overall population [22]. Although our patients received methotrexate and some reports described that the incidence of serious infections in patients with TNF-alpha inhibitor was not significantly higher than those with disease modifying anti-rheumatic drugs (DMARDs) [35,36], two in vivo studies have reinforced the notion of an increasing risk for LD among patients receiving TNF-α inhibitors. First, the administration of a TNF-α-neutralizing antibody to mice in vivo inhibited TNF-α activity and resulted in enhanced L. pneumophila growth in the mouse lung [37].…”

Addressing current treatment challenges in Crohn's disease in real life: A physician's survey

“…Even after extensive world-wide experience with anti-TNF-therapy in IBD and other indications, such as rheumatological or dermatological diseases, there still is some uncertainty about potential risks [9][10][11][12][13] . In the last few years, there has been an increasing trend towards an earlier introduction of TNF-inhibitors (which is associated with a better efficacy 14 ) either via a rapid step up 15,16 or top down 17 , to avoid prolonged steroid exposure and minimizing CDassociated morbidity and the need for surgery.…”

Population Variations in Rheumatoid Arthritis Treatment and Outcomes, Northern California, 1998–2009

“…Recent studies using administrative data have observed increased risk of serious infection, even with low doses of corticosteroid. 21,22 We observed declining use of prednisone during the study period; however, this decline was not linked to a reduction in the rates of pneumonia and opportunistic infection. A difference between this and earlier studies was the design; we did not compare prednisone users with nonusers, which is subject to bias by disease severity, but rather examined changes in both prednisone use and infection risk over time in the population of users and nonusers.…”