Comparing organ‐specific immune‐related adverse events for immune checkpoint inhibitors: A Bayesian network meta‐analysis

Abstract

Dear Editor, Immune checkpoint inhibitor (ICI) drugs have been widely used in clinical practice and have become the firstline treatment regimen for certain tumors, with ICI combination therapies being utilized particularly frequently.1–3 Although the overall incidence of organ-specific immunerelated adverse events (irAEs) is low, such events can sometimes be severe, or even fatal and difficult to predict.4 However, the safety of combination regimens, which is particularly important for improving guidance of clinical treatment decisions, is not clearly understood. Here, we conducted the largest network meta-analysis to comprehensively compare the incidence and safety rankings for common organ-specific irAEs and general adverse events among current immunotherapeutic regimens. We searched all randomized controlled trials involving ICI drugs published in PubMed, Web of Science, and EMBASE from 2010 to June 2020. Eligible studies must have reported detailed irAE information in patients with cancer. The study selection and data extraction procedures are described in the Supplementary Methods. Bayesian network meta-analysis, a random-effects, and consistency model were used to compare the risk of irAEs for different drugs. We used the odds ratio (OR) and 95% credible interval (CrI) as the effect variable for dichotomous variables. Differences with p values less than 0.05 or nonoverlapping 95% CrIs were considered statistically significant. Based on the OR and posterior probabilities, we ranked the risk probability of adverse events for various regimens from high to low. A total of 61 randomized controlled trials that included 34,451 patients were enrolled in the analysis. The baseline characteristics of the included studies and the risk of bias results are shown in Tables S1 and S2. The incidence rates of any grade organ-specific irAEs in patients who received ICI therapy were 8.25% for hypothyroidism, 3.69% for hyperthyroidism, 0.52% for hypophysitis, 1.20%