Evaluation of lung adverse events with nivolumab using the spontaneous reporting system in Japan: a pharmacovigilance study

Abstract

Abstract Purpose: Nivolumab has been widely used in patients since its launch, but detailed information on lung-specific adverse events (AEs) from post-marketing monitoring has not been reported. We therefore conducted this study to examine times to onset, incidence rates, and outcomes of nivolumab-induced lung AEs in patients with cancer, using the Japanese Adverse Drug Event Report database. Methods: We analysed data for the period between April 2004 and March 2021. Data on lung AEs were extracted, and relative risks of AEs were estimated using the reporting odds ratio. Results: We analysed 5,273,115 reports and identified 18,721 reports of AEs caused by nivolumab. Of these, 3,084 lung AEses were reportedly associated with nivolumab. Signals were detected for nine lung AEs (expressed using terminology preferred by the Medical Dictionary for Regulatory Activities): interstitial lung disease; pneumonitis; lung disorder; organising pneumonia; pleural effusion; pneumonia aspiration; pneumonia bacterial; radiation pneumonitis; and infectious pleural effusion. Among these, interstitial lung disease was the most frequently reported (68.7%) and included some fatal cases. A histogram of median times to onset showed AEs occurring from 34 to 79 days after the first dose, but some cases occurred even more than one year after starting administration. Conclusion: We focused on lung AEs caused by nivolumab as post-marketing AEs. Some cases could potentially involve serious outcomes, particularly in interstitial lung disease. Patients should be monitored for signs of the development of these AEs not only at the start of administration, but also over an extended period after starting nivolumab administration.