Systematic analysis of adverse reaction signals induced by Leflunomide, Upadacitinib, and Baricitinib in the treatment of rheumatoid arthritis using the FAERS database

Purpose: Rheumatoid arthritis (RA) stands as a widely recognized chronic inflammatory condition. Leflunomide, upadacitinib, and baricitinib are frequently used to treat inflammatory diseases, but understanding of the adverse events they cause remains limited. This study aims to analyze the mining of adverse drug event (ADE) signals of drugs based on the FAERS database in the United States. Methods: Data were extracted from the FAERS database, including ADE reports from Q1 2004 to Q4 2024. Leflunomide, upadacitinib, and baricitinib-related ADE reports were described and categorized using the Preferred Term (PT) and System Organ Class (SOC) in the International Dictionary of Medical Terms (MedDRA). In baseline characteristics of Leflunomide, Upadacitinib, and Baricitinib, the readxl R package was used for variable analysis. The ggplot2 R package was employed to plot temporal trend line charts of ADE reports for each drug in RA treatment. Results: Baseline analysis showed significant differences in ADE occurrence frequencies among leflunomide, upadacitinib, and baricitinib (p < 0.05). The number of ADE reports for Baricitinib in RA treatment was highest in 2019, that for leflunomide peaked in 2020, and upadacitinib’s ADE reports reached their peak in 2022. Baricitinib-related ADEs in RA treatment included Infections and Infestations, Blood and Lymphatic System Disorders, etc. Leflunomide-related ADEs involved Hepatic Disorders, Congenital, Familial and Hereditary Diseases. Upadacitinib-related ADEs included Surgical and Medical Procedures. Conclusion: This study, based on the FAERS database, identified ADEs in leflunomide, upadacitinib, and baricitinib, which have provided references for improving drug safety and therapeutic efficacy.