Emicizumab use in patients with uncomplicated severe hemophilia A: results of a multicenter Russian study: 616.155.2:615.035

Abstract

Summary. Introduction. Hemophilia A is an inherited disorder characterized by a deficiency or absence of coagulation factor VIII (FVIII), leading to spontaneous or post-traumatic bleeding episodes. The primary therapeutic approach involves regular intravenous infusions of FVIII, carrying a risk of FVIII inhibitor development in 20–30% of previously untreated patients, thereby worsening prognosis and necessitating a change in therapy. Emicizumab was approved in the United States in 2017 and subsequently authorized in the European Union, Japan, and Russia in 2018 for the prophylaxis of bleeding episodes in patients with severe hemophilia A. Aim: to assess the efficacy of prophylactic treatment with emicizumab in reducing the overall frequency and the rate of spontaneous bleeding episodes in patients with hemophilia A without inhibitors, compared with historical data and the results of prior 6-month FVIII therapy. Materials and Methods. А multicenter interventional, non-randomized, uncontrolled, prospective, open-label study was conducted across 6 clinical centers in the Russian Federation from June 2019 to June 2023. The study enrolled male patients aged 18 to 60 years with severe congenital hemophilia A (endogenous FVIII activity < 1%) without FVIII inhibitors, who had been receiving factor replacement therapy either prophylactically or on-demand prior to enrollment. The efficacy of emicizumab therapy was compared with historical control data (6 months prior to study enrollment, obtained from patient medical records) and the results of FVIII therapy during 6 months in the initial study period. The safety was assessed in all patients screened. The study participation for each patient was 90 ± 1 weeks excluding the screening period. Results. A total of 30 patients were screened, and 83.3% (25/30) of them completed the study per protocol. By week 26 of emicizumab therapy, a significant reduction in bleeding episodes was observed: 57.7% of patients experienced no bleeding events (95% confidence interval = 36.9–76.6) during emicizumab therapy compared with 7.7% (p = 0.0003) during FVIII therapy and 11.5% (p = 0.0047) recorded in the historical control. The median annual rate of bleeding requiring treatment was significantly lower during prophylactic emicizumab therapy, with 0 (range: 0.0–19.7) episodes compared with 20.7 (range: 0.0–219.5) episodes during FVIII therapy and 15.0 (range: 0.0–341.2) episodes in the historical control. The study demonstrated comparable safety profiles for FVIII therapy and emicizumab: adverse events (AEs) were reported in 66.7% (20/30) of patients during FVIII therapy and 69.2% (18/26) of patients during prophylactic emicizumab treatment. Most patients experienced mild to moderate AEs during both FVIII and emicizumab therapy periods. No life-threatening AEs or deaths occurred during the study. Conclusion. Emicizumab demonstrated superior efficacy compared with traditional FVIII therapy while maintaining a comparable safety profile.

For citation: Zozulya N. I., Zorenko V.Yu., Polyanskaya T.Yu., Timofeeva M. A., Pospelova T. I., Babaeva T. N., Andreeva T. A., Konstantinova V. N., Ptushkin V. V.
Emicizumab use in patients with uncomplicated severe hemophilia A: results of a multicenter Russian study. Tromboz, gemostaz i reologiya. 2025;(1):98– 109. (In Russ.).

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