Case Report: Relapsed acquired hemophilia A following prednisone-rituximab therapy successfully treated with orelabrutinib

Introduction Acquired hemophilia A (AHA) is a rare autoimmune hemorrhagic disorder characterized by neutralizing autoantibodies against coagulation factor VIII (FVIII). First-line immunosuppressive therapy with corticosteroids with or without rituximab achieves complete remission (CR) in 60-80% of patients; however, relapse occurs in approximately 15-33% of cases after treatment cessation. Management of relapsed AHA remains challenging, with limited evidence for optimal second-line approaches. Bruton’s tyrosine kinase (BTK) inhibitors have emerged as promising agents for antibody-mediated autoimmune diseases. Case description Herein, we report the first case of relapsed AHA successfully treated with orelabrutinib monotherapy after relapse following an initial response to a conventional corticosteroid-rituximab regimen. A 45-year-old male with type 1 diabetes mellitus and hyperthyroidism presented with spontaneous bleeding and was diagnosed with AHA associated with underlying autoimmune endocrinopathies. He achieved complete remission (CR) following prednisone and rituximab but relapsed 3 months after treatment cessation. Orelabrutinib 50 mg orally once daily was initiated as an experimental off-label approach. The patient demonstrated progressive laboratory improvement, achieving a second CR approximately 2 months after orelabrutinib initiation, with undetectable FVIII inhibitor and normalized FVIII activity. Sustained on-treatment remission was maintained throughout 5 months of therapy without bleeding episodes or adverse events, and remission has been maintained after completion of the planned 6-month course and subsequent treatment discontinuation. Conclusion This case supports the therapeutic potential of selective BTK inhibition as a targeted, steroid-sparing strategy in relapsed AHA and highlights the need for prospective clinical trials to validate this approach.