Rituximab as Salvage Therapy in Difficult-to-Treat Autoimmune Hepatitis: A Prospective Case Series.

BACKGROUND AND AIMS: A subset of patients with autoimmune hepatitis (AIH) fail to achieve or sustain a complete biochemical response (CBR) to standard immunosuppression, resulting in a significant unmet clinical need. Rituximab, an anti-CD20 monoclonal antibody, has been investigated in refractory AIH, but prospective data remain limited. We sought to characterize the biochemical response and corticosteroid-sparing effects of rituximab in patients with difficult-to-manage AIH. METHODS: We report a prospective case series of adults with difficult-to-manage AIH enrolled in the Genetic Repository of Autoimmune Liver Disease and Contributing Exposures cohort at Indiana University and treated with rituximab (1000 mg intravenously on days 1 and 15). Eligible patients had refractory disease, corticosteroid dependence, or inadequate biochemical control. Response was assessed at 12, 24, and 48 weeks. CBR was defined as normalization of alanine aminotransferase, aspartate aminotransferase, and immunoglobulin G. Analyses of biochemical outcomes were restricted to patients with active baseline disease. RESULTS: Seven patients were enrolled; 6 had abnormal baseline biochemical indices. Biochemical improvement at 24 weeks was observed in all 6 patients with active baseline disease (100%), with 1 patient (16.7%) achieving CBR. However, response durability was limited, and biochemical worsening between 24 and 48 weeks occurred in 4 of 6 patients (66.7%). Response patterns included insufficient response with subsequent attenuation (n = 4), sustained CBR (n = 1), and early response followed by relapse (n = 1). Median prednisone-equivalent dose decreased from 30 mg/day at baseline to 12.5 mg/day at 48 weeks (-58.3%). No serious adverse events, infections, or hepatic decompensation occurred. CONCLUSION: In this prospective cohort of difficult-to-manage AIH, rituximab produced early biochemical improvement and a sustained corticosteroid-sparing effect, but a durable biochemical remission was uncommon. These data support further prospective evaluation of rituximab and next-generation B-cell-directed therapies in refractory AIH.