Exploring radiation pneumonitis associated with immune checkpoint inhibitors: Insights from the FAERS pharmacovigilance database

The combination of immunotherapy and radiotherapy has become an important strategy for treating thoracic tumors. However, both treatment modalities can cause adverse effects to lung tissue. Research has shown that the concurrent use of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy may result in overlapping toxicities. Therefore, to investigate the association between immune checkpoint inhibitors and the development of adiation pneumonitis (RP), we conducted a retrospective study using the FDA Adverse Event Reporting System (FAERS) database, aiming to provide new insights for clinical practice. We conducted a disproportionality analysis of radiation-pneumonitis-related adverse events associated with ICIs in the FAERS database, covering the first quarter of 2011 through the first quarter of 2025. To ensure the accuracy and reliability of the study, we employed four disproportionality analysis methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN). A total of 1061 ICI-related adverse reactions of RP were included. 716 were male (67.5 %) and 231 were female (21.8 %). The largest group was patients aged 65 and above, accounting for 56.9 % (n = 604). Anti-PD-L1 agents (ROR = 440.92; 95 % CI, 401.52–484.2) had significantly higher reports than anti-PD-1 agents (ROR = 24.13; 95 % CI, 21.1–27.58) and anti-CTLA4 agents (ROR = 19.45; 95 % CI, 13.88–27.93). The median onset time was 29 days (interquartile range [IQR] = 15–57 days). Males were more likely than females to develop ICI-related RP (ROR = 2.13; 95 % CI, 1.84–2.48). Additionally, aged ≥ 65 had a higher likelihood of developing this condition compared to those aged < 65 (ROR = 1.648; 95 % CI, 1.43–1.90). This study comprehensively elucidates the important characteristics of RP associated with various ICIs from the perspective of pharmacovigilance databases. These findings provide clinicians with important insights into understanding the risks and benefits associated with RP when different ICIs are used in combination with radiotherapy.