Freedom From Bleeds With Low-Dose Emicizumab Prophylaxis in Inhibitor-Positive Hemophilia A.

Abstract

Background: The real-world data on outcome of hemophilia A patients with inhibitors (HAI) is sparse, especially from developing countries. In a setting of inequitable healthcare opportunities for hemophilia patients, especially those with inhibitors, low-dose practices of emicizumab are emerging. In the present article, we describe our experience of managing HAI patients on low-dose emicizumab over a period of 56 months (from December 2019 to August 2024).

Methods: The present study reports the response of patients with inhibitor-positive severe hemophilia A (HAI) and a high annual bleed rate to two-dose schedules of emicizumab prophylaxis. All patients with HAI were previously managed with on-demand bypassing agents (BPAs) before being shifted to emicizumab. Seven patients were treated on standard dose of 3 mg/kg weekly for 4 weeks followed by once in 2 weeks, whereas 25 patients were started on low dose of 3 mg/kg once in 4 weeks with or without loading as per clinical decision. Bleed frequency, joint involvement, trough drug level and hemophilia joint health score (HJHS) were documented serially till in September 2023 (median of 16.4 months of follow-up). After September 2023, all patients were shifted to low dose of 3 mg/kg once in 4 weeks, following which 18 more patients were added, and this regimen has continued to date.

Results: Thirty-two patients were initiated on emicizumab prophylaxis between December 2019 and December 2022. The median duration of follow-up of this cohort was 16.4 months (7.7 - 27.3 months). There was a significant reduction in bleed rate and improvement in HJHS in both arms after initiation of emicizumab. During a cumulative follow-up period of 562.8 months involving the 32 patients, only one patient experienced a bleed that required treatment. At 12 months post-initiation, the median baseline HJHS improved from 9 to 0 in children who received full dose and from 12 to 4 in those who received low dose. The mean emicizumab trough level observed in September 2023 in both groups were 29.92 ± 2.53 µg/mL and 12.6 ± 3.79 µg/mL, respectively. No significant difference was noted either in treated bleeds or HJHS score between patients who received standard or low-dose emicizumab. In view of clinical equivalence, the standard-dose patients were also shifted to low dose, and 18 more patients were subsequently added to this arm since September 2023. The last date of follow-up for this analysis was 31 Aug 2024. The cost of treatment on low-dose emicizumab in India compared to on-demand BPAs modeled on a child weighing 10 kg is analyzed.

Conclusions: Emicizumab prophylaxis even in lower doses is effective in preventing bleeds and improving joint outcome in HAI with pre-existing high bleed rate and arthropathy. This opens up an avenue for providing equity in healthcare delivery for HAI in low- and middle-income countries (LMICs) such as India.