Adverse Drug Events Associated with Immune Checkpoint Inhibitors Atezolizumab, Nivolumab and Pembrolizumab: A Descriptive Retrospective Pharmacoepidemiologic Analysis Using FAERS Database 2014-2021

METHODS: The primary data source is the US FDA post-marketing adverse event reporting systems (FAERS) database from 2014 to 2021. We focused on three immune checkpoint inhibitors atezolizumab, nivolumab and pembrolizumab that have been mainly used for liver cancer and other treatments. All adverse events reported to FDA were analyzed with annual trends, frequency of AE reports, and outcomes (e.g., congenital abnormally CA, Death DE, life threatening LT, hospitalization HO, disability DS) for each inhibitor.

RESULTS: Total AE 1,42,374, including Atezolizumab-21,796, Nivolumab- 81,717, and Pembrolizumab- 38,861 reported cases. Key AE outcomes associated with nivolumab - CA-27(0.03%), DE-25550(31.27%), DS-1286(1.57%), HO-32049(39.22%), LT-805(0.99%), with Pembrolizumab – CA-16(0.04%), DE-10806(27.81%), DS-1067(2.75%), HO-15318(39.42%), LT-511(1.31%) and with Atezolizumab – CA-0(0.00%), DE-4642(21.30%), DS-271(1.24%), HO-11159(51.20%), LT-290(1.33%). Most frequently reported cases of malignant neoplasm progression included- 1784(4.59%) with pembrolizumab, 2213 (2.71%) with nivolumab and 30 (0.14%) with atezolizumab. Acute kidney injuries were observed with 1811 (2.22%), 824 (2.12%), and 623 (2.86%) for nivolumab, pembrolizumab, and atezolizumab respectively. Anemia was-associated with Nivolumab 1502(1.84%), pembrolizumab 596(1.53%), and atezolizumab 695 (3.19%)}. Colitis was associated with atezolizumab 307(1.41%), nivolumab 1562(1.92%), and pembrolizumab 532(1.37%) respectively.

CONCLUSIONS: Nivolumab had relatively higher number of AE reports. Some key AE were acute kidney injuries, malignant neoplasm progression, anemia and colitis. More study is needed to evaluate their safety profile and severe outcomes like deaths and hospitalization.