The Risk Factors Associated with Immune Checkpoint Inhibitor-Related Pneumonitis

Background: Pneumonitis is a serious adverse event in patients treated with immune checkpoint inhibitors (ICIs), with a mortality rate of up to 20%. The risk factors for ICI-related pneumonitis remain unclear due to the scarce data and infrequent event rate of 0-10% for all grades in patients using ICIs. Objectives: This study evaluated the risk factors for ICI-related pneumonitis using the United States Food and Drug Administration (US FDA) Adverse Event Reporting System (FAERS) database. Method: To investigate the association between pneumonitis and ICIs, the FAERS database, which contains spontaneous adverse event reports submitted to the US FDA, was utilized. Data between January 2014 and December 2019 were collected. Univariate logistic regression analysis with covariates, including age, sex, and ICI use, was performed to assess the risk of ICI-related pneumonitis. The relative risk of pneumonitis was estimated using by the odds ratio. Results: We identified 4,248,808 reports, including 51,166 cases of those who received eight different ICIs. Nivolumab was the most common ICI (n = 27,273 of 51,166 [53.3%] patients). Reporting rates of pneumonitis were significantly high in ICI users (odds ratio 29.48; 95% confidence interval [CI], 27.49-31.62). Univariate logistic regression analysis showed that pneumonitis risk was significantly associated with age. Age ≤60 years old was associated with an increase in the reported frequency of pneumonitis. Conclusions: Our data suggest that the risk of ICI-related pneumonitis may increase in certain populations, including younger age (age <60 years) and ICIs users. These patients require careful monitoring.