S2649 A Review of Reports of Hepatic Failure and Hepatitis to the FDA Adverse Events Reporting System (FAERS) From Inflammatory Bowel Disease (IBD) Pharmacotherapy

Introduction: Pharmacotherapy of IBD consists of a multitude of medication classifications. This study aims to identify hepatic injury across all treatment modalities of Crohn's disease (CD) and ulcerative colitis (UC) utilizing reports to FAERS. Methods: The FAERS database consists of voluntarily reported post-marketing adverse drug reactions (ADRs). 30,668,520 total reports from Jan 1968 to March 2025 were collected. Reports of ADRs of all FDA approved IBD therapies including azathioprine, mercaptopurine, methotrexate, tacrolimus, balsalazide, mesalamine, osalazine, sulfasalazine, adalimumab, certolizumab pegol, golimumab, infliximab, natalizumab, vedolizumab, guselkumab, mirikixumab, risankizumab, ustekinumab, tofacitinib, upadacitinib, etrasimod, and ozanimod were reviewed. Reports of cases of hepatitis and hepatic failure in the treatment of CD or UC were collected. Using the OpenVigil program, signals for these ADRs were determined using reporter odds ratios (RORs) calculated with the following formula: ROR = (a/c)/(b/d) a: = drug with ADR, b: = all drugs with ADR, c = all ADRs for the drug, d = other drugs with other ADRs. A ROR >1 indicates an ADR frequency is not occurring by chance alone, suggesting a significant post-marketing signal. Results: There were 218 reports of hepatitis, and 135 reports of hepatic failure identified in patients with CD and UC. Azathioprine (ROR 4.26), mercaptopurine (ROR 3.08), and methotrexate (ROR 2.58) showed significant ROR for hepatitis in CD. Mercaptopurine (ROR 3.34), tacrolimus (ROR 21.17), and infliximab (ROR 1.86) showed significant ROR for hepatic failure in CD. Azathioprine (ROR 6.80), mercaptopurine (ROR 9.34), and methotrexate (ROR 4.13) showed significant ROR for hepatitis in UC. Azathioprine (ROR 5.64), tacrolimus (ROR 13.18), and balsalazide (ROR 7.79) showed significant ROR for hepatic failure in UC. Adalimumab demonstrated an apparent protective effect. Conclusion: Analysis of reports to FAERS suggests that azathioprine, mercaptopurine, methotrexate, tacrolimus and infliximab are associated with reports of hepatic injury in patients with CD. Azathioprine, mercaptopurine, tacrolimus, methotrexate, and balsalazide are associated with hepatic injury in patients with UC. Using this method of analysis, adalimumab appears to have a protective effect against hepatic injury in patients with CD and UC.