Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients with Inflammatory Bowel Diseases: a Systematic Review and Meta-analysis

Singh S1, Facciorusso A2, Dulai PS3, Jairath V4, Sandborn WJ3. Clin Gastroenterol Hepatol. 2019 Mar 12. pii: S1542-3565(19)30255-1. doi: 10.1016/j.cgh.2019.02.044. [Epub ahead of print]


Author information

Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: sis040@ucsd.edu.

Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy.

Division of Gastroenterology, University of California San Diego, La Jolla, California.

Division of Gastroenterology, Department of Medicine, University Hospital, Ontario, Canada; Division of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.


BACKGROUND & AIMS: We performed a systematic review and meta-analysis to evaluate the comparative risk of serious infections with tumor necrosis factor (TNF) antagonists, non-TNF targeted biologics, tofacitinib, and immunosuppressive agents in patients with inflammatory bowel diseases (IBD).

METHODS: In a systematic search of publications, through March 18, 2018, we identified 15 observational studies (>500 person-years) of patients with IBD treated with TNF antagonists, non-TNF targeted biologics, tofacitinib, and/or immunosuppressive agents (thiopurines, methotrexate) that reported risk of serious infections. Only studies with active comparators were included, to allow appropriate comparative synthesis. We performed random effects meta-analysis and estimated relative risk (RR) and 95% CIs.

RESULTS: Compared to anti-TNF monotherapy, risk of serious infection increased with the combination of anti-TNF and an immunosuppressive agent (in 6 cohorts; RR, 1.19; 95% CI, 1.03-1.37), with anti-TNF and a corticosteroid (in 4 cohorts; RR, 1.64; 95% CI, 1.33-2.03), or with all 3 drugs (in 2 cohorts; RR, 1.35; 95% CI, 1.04-1.77); there was minimal heterogeneity among studies. In contrast, monotherapy with an immunosuppressive agent was associated with a lower risk of serious infections than monotherapy with a TNF antagonist (7 cohorts; RR, 0.61; 95% CI 0.44-0.84]) or a TNF antagonist with an immunosuppressive agent (2 cohorts; RR, 0.56; 95% CI, 0.39-0.81). Infliximab-based therapy was associated with lower risk of serious infections compared to adalimumab-based therapy in patients with ulcerative colitis (4 cohorts; RR, 0.57; 95% CI, 0.33-0.97), but not Crohn's disease (4 cohorts; RR, 0.91; 95% CI, 0.49-1.70). Few data were available on the comparative safety of biologic agents that do not inhibit TNF and tofacitinib.

CONCLUSIONS: Combination therapies for IBD that include TNF antagonists, especially with corticosteroids, are associated with higher risk of serious infection, whereas monotherapy with an immunosuppressive agent is associated with lower risk, compared to monotherapy with a TNF antagonist. Studies are needed to evaluate the comparative safety of non-TNF targeted biologics and small molecules for treatment of IBD.

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