Emicizumab for acquired haemophilia A: A case series

Abstract

Background Emicizumab is approved to prevent bleeding in patients with congenital haemophilia A with or without inhibitors. However, no randomized trials addressed the efficacy of emicizumab in acquired haemophilia A (AHA). Aims To report the clinical and biochemical response of emicizumab in AHA. Methods This single‐centre retrospective study included seven adults with AHA between November 2020 and May 2022. We collected patient characteristics, laboratory coagulation parameters, the use of haemostatic agents, bleeds and thrombotic events. Treatment was monitored using chromogenic FVIII assays. The assay with human reagents assesses both the emicizumab FVIII‐like‐activity and native patient FVIII‐activity. The assay with bovine reagents only measures the patients’ native FVIII‐activity as emicizumab does not bind to bovine reagents. Results Patients presented with spontaneous hematoma (n = 7), intramuscular bleeding (n = 2), haematuria (n = 2) and/or gastro‐intestinal bleeding (n = 2). Six patients had major bleedings. At diagnosis, APTT was prolonged (91 seconds, IQR 73–103), FVIII activity was 0% (IQR 0–1) and FVIII inhibitor 182 BU/mL (IQR 104–228). Emicizumab was administered weekly (3 mg/kg) for 4 weeks, and thereafter every 2 weeks until regression of the inhibitor. Three patients received activated FVIIa (cumulative dose of 1.7 mg/kg, IQR 1.2‐2.2). All bleedings were controlled after treatment initiation, without further bleeds. After starting emicizumab, FVIII‐like activity reached ≥5% at 12 days (IQR 7–14), whereas recovery of the intrinsic FVIII‐activity ≥5% occurred at 128 days (IQR 88–173), coinciding with the disappearance of the FVIII inhibitor. There were no safety issues. Conclusion In this AHA case series, no new clinically relevant bleeds were observed after initiation of emicizumab in conjunction with standard immunosuppressive therapy.

Innovative Therapies for Acquired Hemophilia A

“…26 In another retrospective single-center case series of seven patients with AHA, the initiation of emicizumab (at a dose of 3 mg/kg weekly for 4 weeks and thereafter at the same dose every 2 weeks) in conjunction with standard immunosuppressive therapy stopped new clinically relevant bleeds with no safety issues. 27 In a prospective, multicenter, open-label phase III study of subcutaneous emicizumab prophylaxis in 12 patients with AHA, no major bleeds occurred in any patient during the treatment, with a single asymptomatic nonserious deep vein thrombosis recorded as a drug-related adverse event. 28 Interestingly, the authors, based on a population pharmacokinetics simulation, used a modified dosing regimen (loading dose of 6 mg/kg on day 1, 3 mg/kg on day 2, followed by a maintenance dose of 1.5 mg/kg once weekly from day 8) compared to that currently approved for congenital hemophilia A (i.e., loading dose of 3 mg/kg/week for 4 weeks followed by a maintenance dose of 1.5 mg/kg/week, 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks from the fifth week onwards).…”