Sex differences in immune-related adverse events with immune checkpoint inhibitors: data mining of the FDA adverse event reporting system

Background Although immune-related adverse events (irAEs) have been reported in patients receiving immune checkpoint inhibitor (ICI) therapy, sex differences in irAEs are not known. Aim The present study described, evaluated and compared differences in irAEs between females and males treated with ICIs. Method irAE reports were obtained from the FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2020. Disproportionality analysis and Bayesian analysis were used to explore differences in irAEs between females and males. The onset time and fatality proportion of irAEs in different ICIs between females and males were further evaluated. Results A total of 30,342 irAE cases were obtained, including 11,097 female cases and 19,245 male cases. Consistent disproportionality signals were detected in females and males, including endocrine toxicity, hepatitis, lung toxicity, nervous system toxicity, and ocular toxicity. Renal toxicity was only detected in male patients receiving ICI therapy (PRR 2.37, 95% CI: 2.25-2.51; IC: 1.24, 95% CI: 1.05-1.43). Males had a longer onset time (females 35 days [IQR 14-87] vs. males 39 days [IQR 14-92], P = 0.041) and higher fatality proportion (females 20.5% vs. males 25.6%, P < 0.01). Conclusions This analysis revealed that males had a higher chance of exhibiting ICI-associated renal toxicity, longer median onset time and worse prognosis of irAEs than females. Greater attention to sex differences in ICI therapy is needed.