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©2017 American Association for Cancer Research.EPub Simpo pdf to word keygen download Download Simpo PDF Password Remover 1.1.0 Portable Navigation: Although fatal irAEs remain rare, AEs should be recognized promptly as early interventions may alleviate future complications. This meta-analysis offers substantial evidence that ICIs are associated with a small but significant increase in risk of selected all-grade irAEs and high-grade gastrointestinal and liver toxicities. Ipilimumab was associated with a higher risk of all-grade rash ( P = 0.006) and high-grade colitis ( P = 0.021) compared with PD-1/PD-L1 ICIs. Rates of high-grade colitis (RR 5.85 P < 0.001) and AST elevation (RR 2.79 P = 0.014) were higher in the ICI arms. Compared with non-ICI arms, ICIs were associated with more all-grade colitis (RR 7.66, P < 0.001), aspartate aminotransferase (AST) elevation (RR 1.80 P = 0.020), rash (RR 2.50 P = 0.001), hypothyroidism (RR 6.81 P < 0.001), and pneumonitis (RR 4.14 P = 0.012). Twenty-one trials were included, totaling 11,454 patients, of whom 6,528 received an ICI (nivolumab, 1,534 pembrolizumab, 1,522 atezolizumab, 751 and ipilimumab, 2,721) and 4,926 had not.
We calculated the incidence and RR of selected all-grade and high-grade gastrointestinal, liver, skin, endocrine, and pulmonary irAEs across the trials using random-effect models. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 19. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab, or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. Immune-related adverse events (irAE) have been described with immune checkpoint inhibitors (ICI), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear.
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