The Real-World Safety and Effectiveness of Rituximab in Preventing Antibody-Mediated Rejection in ABO-Incompatible Liver Transplantation: All-Case Postmarketing Surveillance in Japan

BACKGROUND: In ABO-incompatible (ABOi) liver transplantation, antibody-mediated rejection (AMR) is a challenging post-transplant complication. In Japan, rituximab was approved in 2016 to prevent AMR in ABOi kidney and liver transplantation and in 2023 to prevent and treat AMR in kidney, liver, heart, lung, pancreas, and intestine transplantation. METHODS: We conducted an all-case postmarketing surveillance to assess the safety and effectiveness of rituximab in ABOi liver transplant recipients, with a registration period between February 29, 2016 and May 9, 2021. The safety endpoint was the occurrence of adverse drug reactions (ADRs). The effectiveness endpoints were the AMR-free rates at weeks 4 and 24 post-transplant. Graft survival rates, rejection-free rates (excluding AMR), and survival rates at weeks 24 and 48 were also assessed. RESULTS: In the safety analysis set, 50.3% (91/181) were male, 8.8% (16/181) were aged ≥ 65 years, 12.8% (23/180) were considered at high risk for cytomegalovirus (CMV) infection, and 95.0% (171/180) received a single infusion preoperatively. ADRs and serious ADRs occurred in 65.7% (119/181) and 27.6% (50/181), respectively. ADRs associated with infection occurred in 57.5% (104/181), with CMV infection being the most frequent event. Twenty-four adverse events leading to death occurred in 16 patients, 7 of whom died from 11 ADRs. In the effectiveness analysis set of 183 patients, the AMR-free rate was 93.4% at weeks 4 and 24. At week 48, the graft survival rate was 94.8%, and the survival rate was 90.6%. CONCLUSION: Rituximab had an acceptable safety profile in real-world settings in ABOi liver transplantation.