Analysis immune-related of pembrolizumab adverse events based on the US FAERS database.

Abstract

e24108 Background: Objective To introduce the risk of adverse events (AE) of pembrolizumab and provide a reference for the safe clinical application of this drug. Methods: Pembrolizumab AE reports from January 2014 to December 2023 were collected from the U.S. Food and Drug Administration Adverse Event Reporting System database. A total of 13,312,811 background patients were included in the analysis (38,531,848 adverse events occurred cases), among which the number of patients in the target drug population was 39,847 (116,630 adverse events occurred). The Reporting Odds Ratio (ROR) method and the Proportional Reporting Ratio (PRR) are used to jointly detect signals. The signal judgment threshold is usually a≥3, the lower limit of the ROR95% confidence interval is greater than 1, and the lower bound of the PRR95% confidence interval is greater than 1. When ROR is combined with PRR (using a ≥ 3, PRR ≥ 2 and chi-square value ≥ 4 as the threshold), the intersection of the detection signals of the two methods is defined as a positive risk signal. The preferred system organ classification (SOC) and preferred term (PT) of the latest version of the MedDRA dictionary were used to classify AEs, and the top 30 PTs with AE signal intensity were selected for analysis. Results: a total of 116,630 AE reports with pembrolizumab as the primary suspected drug were collected, involving 5,392 PTs. Calculated using the ROR and PRR combined detection method, a total of 1082 positive PT signals were found. The top 5 risk signals caused by pembrolizumab are immune-mediated hypothyroidism (ROR (95% CI) 499.79 (414.20-603.05), PRR (Chi-Square) 498.61 (54130.8)); Immune-mediated kidney disease (ROR (95%CI) 483.82 (350.34-668.16), PRR (Chi-Square) 483.44 (17753.6); immune-mediated liver disease (ROR (95% CI) 395.30 (346.66-450.77), PRR(Chi-Square)393.65(87426.6)); immune-mediated hyperthyroidism (ROR(95%CI)395.43(266.22-587.36), PRR (Chi-Square) 395.25 (9652.64)), immune-mediated gastritis (ROR (95% CI) 390.20 (253.36-600.95), PRR (Chi-Square) 390.05 (7994.87)); The top five SOCs were systemic diseases and administration site reactions (16636 cases), 10440 cases (8.95%) of gastrointestinal diseases, 8658 cases (7.42%) of benign, malignant and unknown tumors (including cystic and polypoid), 8546 cases (7.33%) of various examinations, and 8506 cases (7.29%) of various injuries, poisoning and operational complications. Conclusions: The risk signal for autoimmune diseases caused by pembrolizumab is relatively strong. It is recommended that clinicians should pay attention to possible autoimmune diseases of various systems during medication.