Journal Article

Infliximab in steroid-refractory immune-related hepatitis does not demonstrate hepatotoxicity and may shorten time on steroids

Weber, Achim, Ramelyte, Egle, Burri, Elias, Mangana, Joanna, Dummer, Reinhard, Cheng, Phil F, Schneider, Alia

2024

Overview

BackgroundImmune-related hepatitis (irHepatitis) is a relatively common immune-related adverse event (irAE) of checkpoint inhibitors. Often, it responds well to steroids; however, in refractory cases, further therapy is needed. Anti-tumor necrosis factor (TNF) antibodies are used for management of multiple irAEs, but there are little data in irHepatitis. Here, we report on safety and efficacy of infliximab in 10 cases of steroid-refractory irHepatitis.MethodsWe retrospectively reviewed patients treated with infliximab for steroid-refractory grade ≥3 irHepatitis at the Department of Dermatology, University Hospital Zurich. The positive response to infliximab was defined as no further increase in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) above 50% than at the time of first infliximab infusion and control of irHepatitis without therapies other than steroids and infliximab.Results10 patients with steroid-resistant irHepatitis grade ≥3 were treated with infliximab 5 mg/kg, of whom 7 (70%) responded positively. In two cases, the liver values increased over 50% before the irHepatitis could be controlled. In another case, therapies other than infliximab and steroids were given. At the median follow-up of 487 days, 90% of the patients demonstrated resolved irHepatitis without AST/ALT elevation following infliximab infusions.ConclusionsTreatment of irHepatitis with infliximab did not result in hepatotoxicity and led to long-lasting positive response in 9 of 10 of the cases. Further research is needed to evaluate the role of anti-TNF antibodies in management of irHepatitis.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Aged / Biopsy / Chemical and Drug Induced Liver Injury - etiology / Clinical/Translational Cancer Immunotherapy / Drug dosages / Female / Hepatitis / Hepatitis - drug therapy / Hepatitis - etiology / Humans / Immune Checkpoint Inhibitors / Infliximab - adverse effects / Infliximab - therapeutic use / Liver / Male / Melanoma / Middle Aged / Monoclonal antibodies / Oncology / Patients / Retrospective Studies / Skin cancer / Steroids / Steroids - therapeutic use / Tumor necrosis factor-TNF