BACKGROUND: The incidence of severe immune-related hepatitis (irHepatitis) Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 under combination therapy with ipilimumab and nivolumab ranges from 15% to 20%. Current clinical guidelines recommend initiating treatment with systemic corticosteroids, followed by second-line immunosuppressants such as mycophenolate mofetil. In contrast, the use of the tumor necrosis factor-α antibody infliximab-commonly administered for other immune-related adverse events such as colitis-is generally not recommended for irHepatitis. A recent single-center study, however, reported the use of infliximab for steroid-refractory irHepatitis in 10 patients without signs of infliximab-associated hepatotoxicity and overall favorable efficacy.This multicenter retrospective analysis aimed to evaluate the safety and efficacy of infliximab in patients with steroid-refractory irHepatitis.

METHODS: A total of 28 patients with advanced cutaneous melanoma and irHepatitis during immune checkpoint inhibitor (ICI) therapy were included from five university hospitals in Germany and one in Belgium. Of these, 27 patients were in American Joint Committee on Cancer stage IV (8th edition).

RESULTS: All patients received ipilimumab plus nivolumab. The Eastern Cooperative Oncology Group performance status was 0 in 75.0% of patients, and nearly all (27/28) developed severe irHepatitis of CTCAE grade 3 or 4 (V.5.0). The median time to onset of irHepatitis was 46 days after first ICI administration. 96.4% of patients were initially treated with systemic corticosteroids. The median interval between onset of irHepatitis and the first dose of infliximab was 23 days. Infliximab was administered intravenously at a dose of 5 mg/kg. 22 patients received one dose, while 6 patients received two doses. In 82.1% of patients, corticosteroids were tapered to less than 5 mg prednisolone equivalent within a median period of 75 days. Clinical remission for irHepatitis (≤CTCAE grade 1) was achieved in 92.9% of patients and was reached after a median time of 21 days following the first infliximab administration. During a median follow-up of 349 days, no deaths or drug-induced liver injury attributable to infliximab were observed.

CONCLUSION: In this retrospective analysis, infliximab appeared to be effective and safe for the treatment of steroid-refractory irHepatitis, with no evidence of hepatotoxicity.