Immune-mediated hepatitis requiring second-line immunosuppression: how long is required? An observational study.

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.