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  • Title: Differential risks of immune-related colitis among various immune checkpoint inhibitor regimens.
    Author: Yao J, Li M, Zhang H, Ge Y, Weygant N, An G.
    Journal: Int Immunopharmacol; 2020 Oct; 87():106770. PubMed ID: 32702598.
    Abstract:
    BACKGROUND: Colitis 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: Our 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.
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