Differential risks of immune-related colitis among various immune checkpoint inhibitor regimens

Abstract

BackgroundColitis is a life-threatening and common immune-related adverse event in patients receiving immune checkpoint inhibitors (ICIs). Therefore, we performed a meta-analysis to assess the risk of immune-related colitis among various ICI treatment regimens. MethodsWe used PubMed, EMBASE, and the Cochrane Library to retrieve phase II or III randomized controlled trials (RCTs) of ICIs that specified the number of all-grade (grade 1–5) colitis and high-grade (grade 3–5) colitis events through January 2020. The pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated to compare the risk of colitis among various therapeutic regimens. ResultsThe search strategy identified 40 RCTs involving 26,893 patients. The risk of all-grade and high-grade colitis after PD-1/PD-L1 inhibitor was significantly lower than that of CTLA-4 inhibitor (0.18 and 0.14 relative risk respectively). The risk of all-grade and high-grade colitis was dose-dependent for CTLA-4 inhibitor therapy, but not for PD-1/PD-L1 inhibitor therapy. The relative risk of all-grade and high-grade colitis after combination therapy with PD-1/PD-L1 inhibitor and CTLA-4 inhibitor compared to PD-1/PD-L1 inhibitor alone was 9.25 and 12.00 respectively. No significant difference was found between PD-1/PD-L1 inhibitor combined with chemotherapy or targeted therapy and PD-1/PD-L1 inhibitor alone for either all-grade or high-grade colitis. ConclusionsOur meta-analysis indicates that CTLA-4 inhibitor is associated with a higher risk of colitis compared with PD-1/PD-L1 inhibitor, whether used as a monotherapy or combination immunotherapy. Importantly, the combination of PD-1/PD-L1 inhibitor with chemotherapy or targeted therapy may not increase the risk of colitis significantly compared to PD-1/PD-L1 inhibitor alone.