Immune-mediated hepatitis requiring second-line immunosuppression: how long is required? an observational study
Cooksley, T. Weaver, J. M. J. Adam, S. Lasserson, D. Lee, R. Lorigan, P.
Cooksley, T.
Weaver, J. M. J.
Adam, S.
Lasserson, D.
Lee, R.
Lorigan, P.
Abstract
BACKGROUND: Immune-mediated hepatitis is a common toxicity and accounts for ⁓20% of immune checkpoint inhibitor (ICI) related deaths. There is broad consensus as to the current approach for acute management for immune-mediated hepatitis. There is little data regarding the duration of immunosuppression in severe immune-mediated hepatitis. METHODS: A prospective observational analysis was performed at a specialist oncology hospital in England from 20th May 2018 to 19th April 2024. The need for second-line immunosuppression, the agents used and their duration were analyzed. The primary outcome was duration of second-line immunosuppression and whether there was a relapse in immune-mediated hepatitis following their cessation. RESULTS: During the study period, 82 patients presented with grade ≥3 immune-mediated hepatitis. Thirty-five (42.7%) had grade 3 hepatitis with 47 (57.3%) having grade 4 hepatitis. All patients received corticosteroids as first line treatment. Twenty-six (31.7%) patients required second-line immunosuppression therapy with mycophenolate mofetil. Four of those required further immunosuppression with a calcineurin inhibitor. The cohort requiring second-line immunosuppression had higher transaminases (mean alanine aminotransferase (ALT) = 889 u/L vs 677 u/L) at presentation. The median duration of therapy was 3 months (6 weeks to 22 months); all patients except for one had stopped their immunosuppression at 6 months. Ten patients who initially received combination ICI therapy had a rechallenge with maintenance nivolumab without a relapse of their hepatitis. CONCLUSION: Most patients with ICI-mediated hepatitis respond to first line immune suppression but approximately one third require second line therapy. Most patients discontinued immune suppression within 3 months. Key messages What is already known on this topic: Hepatitis is a common complication of immune checkpoint inhibition often requiring treatment with steroids and immunosuppression. What this study adds: This prospective observational study of patients presenting with severe ICI induced hepatitis found 26 (31.7%) patients required second-line immunosuppression therapy with a further four requiring third-line agents. The median duration of therapy was 3 months. How this study might affect practice: Most patients with ICI induced hepatitis respond to first line immune suppression but approximately one third require second line therapy, which can often be stopped 3 months post initiation.
Description
Date
2025
Publisher
Collections
Keywords
Type
Article
Citation
Cooksley T, Weaver JMJ, Adam S, Lasserson D, Lee R, Lorigan P. Immune-mediated hepatitis requiring second-line immunosuppression: how long is required? An observational study. Postgraduate medical journal. 2025 Sep 30. PubMed PMID: 41025712. Epub 2025/09/30. eng.