Risk of Serious and Opportunistic Infections Associated With Treatment of Inflammatory Bowel Diseases.

ABSTRACT

BACKGROUND & AIMS: The risk of infection associated with tumor necrosis factor antagonists (anti-TNF) and thiopurines (combination therapy) is uncertain. We assessed the risk of serious and opportunistic infections in patients with inflammatory bowel disease (IBD) treated with thiopurine monotherapy, anti-TNF monotherapy, or combination therapy in a large cohort of patients in France. METHODS: We performed a nationwide population-based study of patients (18 years or older) with a diagnosis of IBD in the French national health insurance database; we collected data from January 1, 2009 until December 31, 2014. The risks of serious and opportunistic infections associated with exposure to combination therapy, anti-TNF, and thiopurine monotherapies were compared using marginal structural Cox proportional hazard models adjusted for baseline and time-varying sociodemographic characteristics, medications, and comorbidities. RESULTS: Among the 190,694 patients with IBD included in our analysis, 8561 serious infections and 674 opportunistic infections occurred. Compared with anti-TNF monotherapy, combination therapy was associated with increased risks of serious infection (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.05-1.45) and opportunistic infection (HR, 1.96; 95% CI, 1.32-2.91). Compared with thiopurine monotherapy, anti-TNF monotherapy was associated with increased risks of serious infection (HR, 1.71; 95% CI, 1.56-1.88), mycobacterial infection (HR, 1.98; 95% CI, 1.15-3.40), and bacterial infection (HR, 2.38; 95% CI, 1.23-4.58, respectively). Conversely, anti-TNF monotherapy was associated with decreased risk of opportunistic viral infection compared with thiopurine monotherapy (HR, 0.57; 95% CI, 0.38-0.87). CONCLUSIONS: In a nationwide cohort study of patients with IBD in France, we found heterogeneity in risks of serious and opportunistic infections in patients treated with immune-suppressive regimens. These should be carefully considered and weighed against potential benefits for IBD treatment in patient management.