Emicizumab versus immunosuppressive therapy for the management of acquired hemophilia A

J Thromb Haemost. 2024 Oct;22(10):2692-2701. doi: 10.1016/j.jtha.2024.06.010. Epub 2024 Jun 25.

Abstract

Background: Acquired hemophilia A (AHA) is an autoimmune bleeding disorder caused by neutralizing antibodies against coagulation factor VIII. Immunosuppressive therapy (IST) is standard of care to eradicate autoantibody production and protect from further bleeding but carries a risk of severe infection and mortality in frail patients with AHA. Recently, emicizumab has been studied for its potential to reduce the need for early and aggressive IST.

Objectives: To compare outcomes of 2 studies that used either IST (GTH-AH 01/2010; N = 101) or prophylaxis with emicizumab (GTH-AHA-EMI; N = 47) early after diagnosis of AHA.

Methods: Baseline characteristics were balanced by propensity score matching. Primary endpoint was the rate of clinically relevant new bleeds during the first 12 weeks; secondary endpoints were adverse events and overall survival.

Results: The negative binominal model-based bleeding rate was 68% lower with emicizumab as compared with IST (incident rate ratio, 0.325; 95% CI, 0.182-0.581). No difference was apparent in the overall frequency of infections (emicizumab 21%, IST 29%) during the first 12 weeks, but infections were less often fatal in emicizumab-treated patients (0%) compared with IST-treated patients (11%). Thromboembolic events occurred less often with emicizumab (2%) than with IST (7%). Overall survival after 24 weeks was better with emicizumab (90% vs 76%; hazard ratio, 0.44; 95%, CI, 0.24-0.81).

Conclusion: Using emicizumab instead of IST in the early phase after initial diagnosis of AHA reduced bleeding and fatal infections and improved overall survival.

Keywords: autoimmune hemophilia; bispecific antibody; bleeding; immunosuppression; inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • 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
  • Female
  • Hemophilia A* / blood
  • Hemophilia A* / diagnosis
  • Hemophilia A* / drug therapy
  • Hemophilia A* / immunology
  • Hemorrhage* / chemically induced
  • Humans
  • Immunosuppressive Agents* / adverse effects
  • Immunosuppressive Agents* / therapeutic use
  • Male
  • Middle Aged
  • Propensity Score
  • Time Factors
  • Treatment Outcome

Substances

  • emicizumab
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Bispecific
  • Immunosuppressive Agents
  • Factor VIII
  • F8 protein, human

Supplementary concepts

  • Factor 8 deficiency, acquired