The use of emicizumab in children with hemophilia A without inhibitors in the real-world clinical setting

Abstract

In our country, the use of emicizumab in children with hemophilia A without inhibitors (HA) in the real-world clinical setting is limited and is available only as few individual case reports. Our aim was to evaluate the effectiveness and safety of the prophylactic use of emicizumab in children with severe HA in the real-world clinical setting. We conducted a retrospective analysis of medical records of children with HA who had received emicizumab at 9 centers based in the Russian Federation. We assessed the annualized bleeding rate (ABR), annualized spontaneous bleeding rate (ASBR), annualized joint bleeding rate (AJBR), annualized bleeding rate for bleeding episodes that required additional treatment with FVIII concentrate (ABRRT) and the number of hospital admissions for bleeding both before and after the treatment with emicizumab, as well as the occurrence and severity of adverse events during the therapy. Ethics committee approval was not required for this study because it involved the use of aggregated retrospective data from routine clinical practice that were fully anonymized. Two emicizumab administration regimens were compared with regard to their effectiveness. Before the treatment with emicizumab, ABR was 5.38 (95% confidence interval (CI) 3.90–7.64), ASBR – 4.16 (95% CI 2.99–5.94), AJBR – 2.7 (95% CI 1.87–4.03), and ABRRT – 4.8 (95% CI 3.37–7.08). After the initiation of the treatment with emicizumab, the bleeding rate plummeted: ABR decreased by 93.9% (95% CI 88.8–96.7), ASBR – by 96.9% (95% CI 93.1–98.6), AJBR – by 96.1% (95% CI 90.4–98.4%) and ABRRT – by 95.1% (95% CI 90.0–97.6). During the treatment with emicizumab, the rate of bleeding episodes that required hospital admission decreased from 1.58 (95% CI 0.98–2.68) to 0.04 (0.01–0.10), which amounted to 97.6% (95% CI 91.1–99.4). The median follow-up time for the patients treated with emicizumab was 15.5 months (range 9–29 months). When comparing the annualized bleeding rates in the groups of the patients who were preventively treated with emicizumab at doses of 3 mg/kg (administered once every 2 weeks) and 1.5 mg/kg (once per week), we didn't find any statistically significant differences. In the real-world clinical setting, the use of emicizumab in the children with HA led to a significant reduction in all bleeding episodes (by more than 90%), regardless of the administration regimen.