Summary Analysis of HAVEN 1–4 and Patient Case Studies from ÚHKT
MUDr. Věra Geierová from the Institute of Hematology and Blood Transfusion in Prague prepared a summary of what was discussed about emicizumab during the ASH 2020 congress for this year's Prague Hematology Days. In this context, she highlighted the comprehensive analysis of phase 3 HAVEN 1–4 studies, which assessed the safety and efficacy of emicizumab in individuals with hemophilia A with or without FVIII inhibitors.
Key Findings
The author highlighted the following points:
- During almost 3 years of follow-up, emicizumab led to a very low incidence of treated bleeds in individuals with hemophilia A of all age groups, whether with or without inhibitors.
- Over time, there was a decrease in the annual incidence of bleeds, an increase in the proportion of participants who had no treated bleeds, and a resolution of bleeding episodes in almost all previously affected joints.
- Emicizumab was well tolerated over the long observation period, and no new safety risks were characterized in this analysis. Long-term safety and efficacy data were consistent with findings from primary analyses and showed a continued reduction in the incidence of bleeds with long-term treatment.
Emicizumab at ÚHKT
Treatment with emicizumab began at ÚHKT in 2020 for 2 patients with FVIII inhibitors due to recurrent bleeds during existing treatment and the resultant decrease in quality of life.
Case Study 1
Patient aged 80 years:
- Moderate hemophilia A (FVIII < 2%).
- Long-term follow-up in hematology outside hemophilia centers, treated only once with FVIII concentrate (tooth extraction) until age 77; had repeated untreated joint bleeds and signs of advanced hemophilic arthropathy.
- 11/2017: significant traumatic bleed into the right leg muscles, required hospitalization and intensive therapy with recombinant FVIII.
- 3/2018: FVIII inhibitor detected (20 BU/ml), immunotolerance therapy (ITI) started after 3 months.
- During almost 2 years of ITI, the patient experienced several bleeds, mainly into soft tissues (treated with rFVIIa), one significant venous access complication.
- During ITI, a gradual decrease in inhibitor level was observed below 2 BU/ml, but from early 2020, a new rise to 30 BU/ml was noted.
- April 1, 2020: emicizumab administration started, switched to bi-weekly dosing after loading phase.
- 6/2020: traumatic bleed into the right forearm, reported a week late, hematoma resolved in 2 weeks without further therapy.
Case Study 2
Patient aged 37 years:
- Severe hemophilia A, FVIII inhibitor present since childhood.
- Gradual development of severe hemophilic arthropathy, wheelchair-bound since age 17, repeated attempts at verticalization and walk rehabilitation with only temporary success.
- Long-term prophylactic therapy with bypassing agent, despite this, averaged 1–2 bleeding episodes per month (spontaneous and traumatic).
- 11/2020: emicizumab administration started, switched to bi-weekly dosing after loading phase.
- A month after starting emicizumab prophylaxis, had a traumatic bleed into the palm, which stopped without needing additional hemostatic therapy.
Unanswered Questions
According to MUDr. Geierová, issues to address in the future include ensuring major surgical procedures for patients with FVIII inhibitors (as there is currently little experience in this area) and the potential pro-thrombotic risk of emicizumab in older hemophilia A patients without FVIII inhibitors.
Eva Srbová
Editorial Office MeDitorial
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