Real-world impact of emicizumab and immunosuppression on acquired hemophilia A: a multicenter US cohort

Blood Adv. 2024 Nov 26;8(22):5896-5905. doi: 10.1182/bloodadvances.2024013882.

Abstract

Acquired hemophilia A (AHA) is an autoimmune bleeding disorder that is caused by factor VIII (FVIII) autoantibodies with high morbidity and mortality due to bleeding and complications from immunosuppression (IST). To address the real-world implications of the FVIII mimetic antibody, emicizumab, and the role of IST, we retrospectively collected de-identified data on 62 patients with AHA who were treated off-label with emicizumab for a median of 10 weeks at 12 US-based hemophilia treatment centers. Most patients (95.2%) had acute bleeding at diagnosis, and 62.9% had partial or no control of bleeds despite the use of hemostatic agents at the time emicizumab was started. The main reason for initiating emicizumab was outpatient bleeding prophylaxis. After initiation of emicizumab, 87.1% had no additional bleeds. There were 6 breakthrough bleeds (2 spontaneous) in 5 patients and no fatal bleeding events during maintenance emicizumab treatment. The mean breakthrough bleed rate per patient-week was 0.02 (95% confidence interval, 0.0-0.03) during the first 12 weeks of emicizumab for the 55 patients with at least 12 weeks of follow-up. Of these patients, 92.7% received IST and 74.5% were prescribed rituximab-based regimens. Complete resolution of inhibitor and normalization of FVIII levels occurred in 56% overall and in 63% of the patients treated with rituximab. Overall, the median time to discontinuation of emicizumab and IST was 18 weeks. Two patients had thrombotic events while on emicizumab, but no adverse events were attributed to emicizumab and there were no infections attributed to IST. Emicizumab provides effective outpatient bleeding prophylaxis for AHA, and concurrent IST may further mitigate bleeding.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bispecific* / adverse effects
  • Antibodies, Bispecific* / therapeutic use
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Factor VIII / immunology
  • Factor VIII / therapeutic use
  • Female
  • Hemophilia A* / drug therapy
  • Hemorrhage / etiology
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Retrospective Studies
  • United States

Substances

  • emicizumab
  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • Factor VIII
  • Immunosuppressive Agents

Supplementary concepts

  • Factor 8 deficiency, acquired