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

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.

The future of bypassing agents for hemophilia with inhibitors in the era of novel agents

“…As we wait for a cure for hemophilia, and information on how a cure may apply to inhibitor patients, these new agents may transform the treatment of inhibitor patients and inhibitor‐related bleeds, potentially decreasing morbidity and mortality and improving patients’ quality of life . Traditional bypassing agents improved patient convenience and clinical outcomes when they were first introduced; now the combination of bioengineered bypassing agents and novel prophylaxis agents may do the same once again.…”

Boosting therapeutic potency of antibodies by taming Fc domain functions

“…Emicizumab, developed by Chugai Pharmaceutical, is an IgG4 knobsinto-holes bispecific for coagulation factors IX and X to mimic coagulation factor VIII (FVIII) activity and is more favorable than FVIII in terms of pharmacokinetics (21 days for emicizumab vs. 0.5 day for FVIII) 121 . The Fcengineered bispecific IgG4 antibody, emicizumab has been approved by the FDA for prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A on November 2017 [122][123][124] . This Fc engineering for bispecificity enabled co-ligation of two different antigens and opened up new therapeutic opportunities, maintaining all of the beneficial properties of mAbs.…”

Unsolved issues of providing medical care to patients with hemophilia with inhibitors in Russia

“…Эмицизумаб обладает благоприятным профилем безопасности, значительно повышает качество жизни пациентов: уменьшаются боль при движении, болезненная отечность, боль в суставах, больным становится легче ходить [21]. По данным анкетирования пациентов, лишь 16,3 % больных с ИФГ не чувствуют боли и дискомфорта, при этом доля таких пациентов снижается (на 3,7 % в 2017 г. по сравнению с результатами анкетирования 2010 г.)…”