Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors: A Scoping Review

Background: The heterogeneity of immune-related adverse events (irAEs) in real-world evidence highlights the need to identify patterns, knowledge gaps, and priorities for future research. Objectives: To assess in labels the expected irAEs associated with immune checkpoint inhibitors (ICIs) in lung cancer, melanoma, breast cancer, and colon cancer and evaluate their incidence, clinical characteristics, management, and outcomes in real-world studies. Methods: Medicine Agency data sources (Food and Drug Administration and European Medicines Agency) were assessed for labeled irAEs associated with ICIs, and a comprehensive literature review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for scoping review was performed by retrieving observational and target trial emulation studies conducted using data collected in administrative healthcare databases (AHDs) and in spontaneous reporting systems (SRSs) concerning the drugs and tumors of interest from PubMed. irAEs' incidence, onset, management, and outcomes were retrieved. Results: ICI combination therapy increases irAE occurrence, and inter-agency differences emerged. From PubMed, 49 observational studies were included, 22 on SRSs and 27 on AHDs. The ICIs most frequently evaluated were pembrolizumab and nivolumab, and the irAEs most reported were "lower respiratory tract disorders (excluding obstruction and infection)" (SRSs) and "epidermal and dermal conditions" (AHDs) for both drugs. Missing information on survival analysis, therapy dechallenge and rechallenge, concomitant therapies, comorbidities, time to onset, and duration of irAEs were highlighted. Conclusions: This scoping review highlights the complex, multi-organ irAEs from ICIs, underlining the need for tailored monitoring and management based on both regulatory and real-world evidence.