S1614 Adverse Events of JAK Inhibitors in IBD: An FAERS Database Study

Introduction: Janus Kinase inhibitors (JAKI) are small molecule drugs prescribed for myeloproliferative disorders and immune mediated inflammatory diseases, including inflammatory bowel disease (IBD). Tofacitinib is approved for ulcerative colitis (UC); upadacitinib for both UC and Crohn’s Disease (CD). JAKIs have an Food and Drug Administration-issued black box warning for serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis, which was due to the ORAL Surveillance study demonstrating higher rates of malignancy and MACE in rheumatoid arthritis (RA) patients prescribed tofacitinib compared to anti-TNF agents. Subsequent studies have not confirmed these findings in IBD patients. This study is the first pharmacovigilance study evaluating the FDA Adverse Event Reporting System (FAERS) for Adverse Drug Events (ADE) related to JAKI specifically in the IBD population. Methods: A retrospective pharmacovigilance analysis of tofacitinib (for UC) and upadacitinib (for UC and CD) was performed. We evaluated ADEs related to the black box warning for JAKIs. We utilized the FAERS database and Open Vigil 2.1 for data extraction, using MedDRA search terms. Reporting Odds Ratio (ROR) was employed for disproportionality analysis to distinguish true ADE signals from normal background noise. All available cases meeting inclusion criteria were included through March 30, 2025. Results: We found significant signals using ROR in both JAKI in pulmonary embolism (PE): upadacitinib in UC (3.278, 95% CI 2.44-4.41), upadacitinib in CD (3.88, 95% CI 2.67-5.66), tofacitinib in UC (1.74, 95% CI 1.29-2.36). Upadacitinib had significant signals for malignancy in CD (ROR 1.61, 95% CI 1.32-1.96), non-melanoma skin cancer (NMSC) in UC (ROR 2.196, 95% CI 1.55-3.11), DVT in CD (ROR 3.02, 95% CI 1.60-5.70), and cerebrovascular events in UC (ROR 1.60, 95% CI 1.15-2.21). Tofacitinib was found to have statistically significant reporting in DVT (ROR 1.9; 95% CI 1.295-2.788). There were no statistically significant signals identified for MACE, serious infections, lymphoma, or lung cancer. Conclusion: Our findings suggest statistically significant disproportionality in the reporting of thrombotic events (PE and DVT), cerebrovascular events (which may be related to thrombotic risk) and malignancy (including NMSC). Notably there was no increased signaling for MACE or serious infections, contrary to the black box warning for JAKI. Prospective studies are needed to clarify the risks associated with JAKIs in the IBD population.