Analysis of Immune-Related Adverse Events of Pembrolizumab Using FAERS Database.

Introduction: Pembrolizumab is a PD-1 inhibitor that has been approved for the treatment of melanoma, non-small cell lung cancer, esophageal cancer and other malignant tumors. The safety profile of pembrolizumab across a broad patient population over an extended timeframe remains unverified. This study aims to investigate the adverse events (AEs) related to pembrolizumab and provide references for its safe and rational clinical use.

Methods: The study used FDA Adverse Event Reporting System (FAERS) data reported from July 2014 to September 2023, Risk estimation was conducted using the proportional reporting ratio (PRR). AEs were classified and analyzed according to the system organ class (SOC) and preferred term (PT) from the Medical Dictionary for Regulatory Activities (MedDRA).

Results: A total of 37,511 AE reports were identified, involving 5,259 PTs and 22 SOCs. Using the PRR method, 931 positive signals were detected. The top 10 risk signals were all immune-related AEs (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, investigations, gastrointestinal disorders, respiratory, thoracic, and mediastinal disorders, and injury, poisoning, and procedural complications. The median time to onset of AE was 25 days (interquartile range [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 erythrodysesthesia 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 toward the potential occurrence of irAEs at the initial stages of drug administration, with appropriate measures implemented as necessary.