Immune-related adverse events in older adults: Data mining of the FDA Adverse Event Reporting System

Introduction: Recent studies reveal that there is no difference in the efficacy of immune checkpoint inhibitors (ICIs) between younger adults and older adults. However, it remains unclear whether age is a risk factor for immune-related adverse events (irAEs). Materials and methods: To analyze the association between irAEs and age based on data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 2004 and December 2020, we performed a case/noncase study on ICI-related adverse events. Cases were defined as adverse event cases with ICI therapy and irAEs, and noncases were defined as adverse event cases with ICI therapy and without irAEs. One case was matched to a noncase using the sex, reporter, report year, and type of ICI regimen. The reporting odds ratios (RORs) were used to assess the disproportionality of irAEs between older adults (>= 65 years) and younger adults (< 65 years). Results: The study shows that compared with younger adults, the ROR of older adults was 1.12 (95% confidence interval [CI]: 1.08-1.16) and 1.18 (95% CI: 1.14-1.23) before and after matching, respectively. The signal of age -related irAEs was detected in patients treated with ICI monotherapy but not in patients treated with combination therapy. Further analysis revealed a spectrum of age-related toxicities including cardiovascular toxicities, lung toxicities, musculoskeletal toxicities, nervous system toxicities, renal toxicities, and skin toxicities. Conclusion: In this analysis performed based on the FAERS, irAE cases were more likely to be reported in older adults. Our pharmacovigilance study complements the safety data of clinical trials. Further studies are expected to explore the underlying reasons for irAEs in older adults.