Post-Marketing Safety Experience of Vedolizumab in Patients With Pre-existing Viral Hepatitis

Abstract

Introduction: Systemic immunosuppressive treatment can reactivate the latent hepatitis virus.1 The gut selectivity of vedolizumab (VDZ) may be associated with a lower risk of hepatitis virus reactivation than anti-tumor necrosis factor-alpha agents. The VDZ US Product Label advises caution in patients with a history of recurring severe infections.2 As VDZ clinical trials excluded patients with chronic viral hepatitis B or C, there are no clinical trial data available in this population. Here, we describe the VDZ safety experience in patients with pre-existing hepatitis B or C in the post-marketing setting. Methods: Adverse events (AEs) were identified from the VDZ Global Safety Database (data cut May 20, 2014 to Nov 19, 2016) and included if patients' medical history or concurrent conditions included a Medical Dictionary for Regulatory Activities (MedDRA) preferred term of hepatitis B or C infection. Results: In the context of ˜77,382 patient-years of VDZ post-marketing exposure (30,470 AEs), 15 patients (n=7 Crohn's disease; n=6 ulcerative colitis; n=2 indication not reported [NR]) with hepatitis B (n=5, including 2 chronic) or C (n=10) infection were identified. Eight patients received prior/concomitant anti-tumor necrosis factor-alpha therapy; NR n=2. 51 AEs (n=13 serious [non-fatal]; n=38 non-serious) were reported, reflecting the general VDZ safety profile in patients without viral hepatitis. Liver-related events were reported in two patients with hepatitis C: one patient who was a smoker reported hepatic neoplasm; the other reported hepatic mass and had a history of skin cancer, cholecystectomy, bladder tumor removal, and right radical orchidectomy. Of events with a reported outcome, 22/26 (84.6%) were resolved/resolving and 4/26 (15.4%) were unresolved at the time of reporting; NR n=25. VDZ was continued in 10/14 (71.4%) patients and discontinued in 4/14 (28.6%); NR n=1. Conclusion: There was no evidence of increased risk of viral reactivation in patients with hepatitis B or C receiving VDZ. Limitations associated with post-marketing safety reporting and currently limited availability of VDZ in regions with endemic hepatitis B and C should be considered when interpreting these results.