Emicizumab Efficacy in Severe Hemophilia (A): Experience in Ecuador

Abstract

Introduction: In Ecuador, there are 1708 cases of hemophilia in a population of 17,643,060 habitants; according to the World Federation of Hemophilia (WFH) Annual Global Survey Report 2020 released in October 2021. Eleven patients use emicizumab in Ecuador (ten patients under ministerial authorization, and one patient through private insurance); being the first administered in June 2021. Objectives: To describe the demographic characteristics of patients receiving emicizumab in Ecuador. To determine efficacy and response with emicizumab: based on annual bleeding rate (ABR), performance status assessment, activity, and participation. Methods: Population: Pediatric Severe Hemophilia A (PwHA) patients (<12 years) and adults/adolescents (>12 years), both from the public and private health sector. Study design: Retrospective, multicentric study, with a case-report research design. The sources of information were the medical records of the patients. Efficacy variables: ABR was calculated by: (number of bleeds/number of days times 365.25). Body structure and function was assessed with the Hemophilia Joint Health Score 2.1 (HJHS). Activity and participation were assessed with the Functional Independence Score in Hemophilia (FISH). Statistic analysis: Shapiro-Wilk test to know the distribution of the sample, t-Test paired tests (parametric), Wilcoxon statistic (non-parametric); Descriptive statistics: relative frequencies, measures of central tendency and dispersion, column graphs. Analysis and results: Ten patients with an average (Q1,Q3) age of 11.5 years (7.15) were registered. The youngest patient was one year old and the oldest, fifty years old. 90% (n:9) had hemophilia A with high-response inhibitors. Prior to starting emicizumab: 20% (n:2) presented Central Nervous System bleeding, 30% (n:3) had muscle bleeding, and 10% (n:1) developed catheter-associated infection. The mean ABR was 10 pre-emicizumab events, and 0.3 post-emicizumab events (p=0.002), with follow-ups at 22 months (n: 2), 17 months (n:2), 3 months (n:2 ), 4 months (n: 3), 5 months (n: 1). The mean HJHS (±SD, n) was 20.9 (± 20,096, 10) pre-emicizumab, and 9.7 (± 16.52, 10) (p=0.003) The mean by FISH (±SD, n) was 16.2 (± 8.59, 10) pre-emicizumab, and from 22.6 (± 11.62, 10) with the use of emicizumab. The use of the t-Test for paired samples determined that there are statistically significant differences between the pre-emicizumab and post-emicizumab groups for the variables ABR, HJHS and FISH (95% confidence level). Conclusion: The use of Emicizumab allowed better control of joint bleeding; and it contributed favorably in the evolutionary course of both the functional state and the activity. It is essential to corroborate these results with a longer follow-up and a larger sample size. Bibliography: 1. Alvarez Roman M: Spanish guidelines for the management of hemophilia. 2022, 1-190. 2. Callaghan M, Negrier C, Paz-Priel I, Chang T, Chebon S y col: Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137(16):2231-2242 3. Carcao M, Escurriola C, Santagostina E, Oldenburg J, Liesner R y col: The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab. Haemophilia. 2019;25:676-684. 4. Ellsworth P, Ma A: Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?. Hematology Am Soc Hematol Educ Program. 2021, Dec 10;2021(1):219-225. 5. Young G: Management of children with hemophilia A: How emicizumab has changed the landscape. Journal of Thrombosis and Haemostasis. 2021 Jul;19(7):1629-1637