The effect of emicizumab prophylaxis on health-related outcomes in persons with haemophilia A with inhibitors: HAVEN 1 Study

Haemophilia. 2019 Jan;25(1):33-44. doi: 10.1111/hae.13618. Epub 2018 Nov 14.

Abstract

Introduction: Persons with haemophilia A (PwHA) with inhibitors to factor VIII often experience decreased health-related outcomes. In HAVEN 1 (NCT02622321), there was a statistically significant reduction in bleeding with emicizumab prophylaxis versus no prophylaxis.

Aim: Describe health-related outcomes in PwHA with inhibitors in HAVEN 1.

Methods: PwHA with inhibitors aged ≥12 years previously on episodic bypassing agents (BPAs) were randomized to emicizumab prophylaxis (Arm A; n = 35) or no prophylaxis (Arm B; n = 18); participants previously on BPA prophylaxis received emicizumab prophylaxis (Arm C; n = 49). Health-related outcomes assessed at baseline and monthly thereafter: Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), Haemophilia-specific Quality of Life Questionnaire for Children Short Form (Haemo-QoL SF), EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) index utility score (IUS) and visual analogue scale (EQ-VAS) and work/school days. Days hospitalized also recorded.

Results: At week 25, differences (ANCOVA) in adjusted mean scores (95% confidence interval) favoured Arm A versus B for Haem-A-QoL "Total" score (14.0 [5.6, 22.5]; P = 0.002) and "Physical Health" (21.6 [7.9, 35.2]; P = 0.003); EQ-VAS (-9.7 [-17.6, -1.82]; P = 0.017); and IUS (-0.16 [-0.25, -0.07]; P = 0.001); mean scores are comparable in Arms A and C. Throughout the study, a greater proportion of participants on emicizumab prophylaxis than no prophylaxis exceeded questionnaire-specific responder thresholds. Mean proportion of missed work days and number of days hospitalized were lower with emicizumab prophylaxis than no prophylaxis.

Conclusions: In PwHA with inhibitors, emicizumab prophylaxis was associated with substantial and meaningful improvements in health-related outcomes.

Keywords: emicizumab; factor VIII inhibitors; haemophilia A; health-related quality of life; prophylaxis.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Bispecific / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Child
  • Factor VIII / antagonists & inhibitors
  • Health Status
  • Hemophilia A / drug therapy*
  • Hospitalization
  • Humans
  • Isoantibodies / blood*
  • Male
  • Middle Aged
  • Quality of Life*
  • Young Adult

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • Isoantibodies
  • emicizumab
  • Factor VIII