Gastrointestinal safety signals of Janus kinase inhibitors: a real-world pharmacovigilance study using Food and Drug Administration Adverse Event Reporting System

BACKGROUND: Janus kinase inhibitors (JAKis) are increasingly used in dermatology, yet their gastrointestinal safety profiles remain incompletely characterized in real-world practice. Although gastrointestinal adverse events (GIAEs) are generally mild, gastrointestinal perforation remains an important safety concern with JAKi treatment. This study aimed to characterize GIAEs associated with six oral JAKis and identify potential disproportionality signals in the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: GIAEs associated with abrocitinib, baricitinib, deucravacitinib, ritlecitinib, tofacitinib, and upadacitinib were evaluated. System Organ Class-level reports and patient characteristics were obtained from AERSMine, while Preferred Term-level disproportionality analyses were performed using OpenVigil 2.1. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated; signals were considered positive when the lower 95% CI exceeded 1. RESULTS: Overall, 74,678 GIAE reports were identified, predominantly for tofacitinib and upadacitinib. Diarrhea, nausea, and vomiting were among the most frequently reported events. Positive signals included nausea and abdominal discomfort with abrocitinib, diarrhea with ritlecitinib, and diarrhea and abdominal discomfort with tofacitinib. The strongest signals predominantly involved gastrointestinal infections and perforation-related events. CONCLUSIONS: This study highlights potential gastrointestinal safety concerns associated with JAKis. Further real-world observational studies are needed to clarify their clinical significance.