Systematic review with meta-analysis: biologics and risk of infection or cancer in elderly patients with inflammatory bowel disease

Background Uncertainty exists concerning the risk of infection and cancer associated with biologic therapies in elderly patients with inflammatory bowel disease (IBD). Aims To identify, synthesise and critically appraise the available evidence on the topic. Methods We systematically searched Medline/PubMed, Embase and Scopus, through October 2019, and recent conference proceedings, to identify studies investigating the risk of serious infections, opportunistic infections, any infection and cancer in elderly IBD patients (>60 years) exposed to biologics as compared to those unexposed to biologics. Two reviewers independently extracted study data and assessed each study's risk of bias. We examined heterogeneity, and calculated summary effect estimates using fixed- and random effects models. Quality of evidence was determined with GRADE. Results We included 15 studies (one post hoc analysis of a randomised trial, nine cohort and five case-control studies). Elderly IBD patients treated with biologics were at increased risk of developing serious infections (random effects summary relative risk: 2.70, 95% CI: 1.56-4.66; seven studies; I-2 = 57%) and opportunistic infections (3.16, 1.09-9.20; four studies; I-2 = 73%). The occurrence of any infection (1.67, 0.51-5.43; five studies; I-2 = 75%) and cancer (0.90, 0.64-1.26; nine studies; I-2 = 0%) was not significantly affected. Nevertheless, our confidence in the effect estimates is rather limited; the quality of evidence is low to very low. Conclusions Biologics are likely to increase the risk of serious and opportunistic infections in old IBD patients. Large prospective studies are needed to further assess the biologic treatments' long-term safety profile in this population.