Analysis of immune related adverse events of pembrolizumab using FAERS database

Objective: This study aims to investigate the risk signals associated with pembrolizumab and provide references for its safe and rational clinical use. Methods: Data on adverse events (AEs) related to pembrolizumab, reported from July 2014 to September 2023, were extracted from the US FDA Adverse Event Reporting System (FAERS) database. Data mining was conducted using the Proportional Reporting Ratio (PRR) method. AEs were classified and analyzed according to the System Organ Class (SOC) and Preferred Term (PT) from the Medical Dictionary for Regulatory Activities (version 26.1). Results: A total of 37,511 AE reports related to pembrolizumab were identified, involving 5,259 PTs and 22 SOCs. Using the PRR method, 931 positive signals were detected. The top 10 risk signals for pembrolizumab were all immune-related adverse events (irAEs) and important medical events (IMEs). The five PTs with the highest signal intensity were immune-mediated hypothyroidism, immune-mediated renal disorder, immune-mediated hepatic disorder, immune-mediated gastritis, and immune-mediated hyperthyroidism. The leading SOCs involved in AE reports were general disorders and administration site conditions (8,184; 14.11%), investigations (5,333; 9.19%), gastrointestinal disorders (4,962; 8.55%), respiratory, thoracic, and mediastinal disorders (4,937; 7.57%), and injury, poisoning, and procedural complications (3,611; 6.22%). The median time to onset of AE was 25 days (IQR 6-85 days), with the Weibull distribution test indicating an early failure-type curve. Gender and age analysis revealed that women were more likely to develop hypertension, alopecia, headache, hypothyroidism, and palmar-plantar erythrodysaesthesia syndrome, whereas men were more likely to develop interstitial lung disease, renal impairment, and death. Additionally, neutropenia was more prevalent in patients under 65 years of age, while interstitial lung disease and renal impairment were more common in patients aged 65 and above. Conclusion: Significant age- and gender-related differences were observed in AE signals with pembrolizumab, particularly for irAEs. Clinical attention should be directed towards the potential occurrence of irAEs at the initial stages of drug administration, with appropriate measures implemented as necessary.