rFVIIIFc v léčbě hemofilie A z pohledu reálné klinické praxe tří center pro léčbu hemofilie v České republice
Authors:
E. Zápotocká 1,2; S. Köhlerová 3; G. Romanová 1,4; P. Smejkal 4
Authors‘ workplace:
LF MU, Brno 2 Klinika dětské hematologie a onkologie FN Motol, Praha 3 Oddělení dětské hematologie a biochemie, FN Brno 4 Oddělení klinické hematologie a Katedra laboratorních metod LF MU a FN Brno
1
Published in:
Transfuze Hematol. dnes,29, 2023, No. 2, p. 134-141.
Category:
Original Papers
doi:
https://doi.org/10.48095/cctahd2023prolekare.cz6
Overview
Introduction: In haemophilia A, prophylaxis using factor VIII preparations with an extended biological half-life (EHL) is gradually gaining ground over standard half-life factors (SHL). One of representative of EHL is efmoroctocog alfa (rFVIIIFc). Objective: Retrospective evaluation of the transition from SHL to rFVIIIFc treatment in the routine clinical practice at three complex haemophilia centres in the Czech Republic. Methods: Retrospective analysis of medical records of patients with severe haemophilia A in two age groups (< 12 and ≥ 12 years) previously treated with prophylactic SHL who were switched to rFVIIIFc. We evaluated bleeding control, injection frequency, factor consumption and attained trough levels. Results: 16 patients with an average age of 6.1 years were included in the group < 12 years, and 8 patients with an average age of 37.8 years were included in the group ≥ 12 years. Group < 12 years: Compared with SHL, treatment with rFVIIIFc resulted in a statistically significant reduction in the mean annual ABR bleeding rate (2.69 ± 2.24 vs. 0.69 ± 1.02; P = 0.0015) and the number of weekly applications (3 ± 0.45 vs. 2.21 ± 0.29; P = 0.0008). The proportion of patients without bleeding increased from 12.5% to 62.5%. Factor consumption was similar and differences in mean trough levels (%) were not statistically significant (1.37 ± 0.85 vs. 1.66 ± 0.79). Group ≥ 12 years: Compared to SHL, treatment with rFVIIIFc led to a statistically significant decrease in the mean number of applications (2.62 ± 0.62 vs. 1.88 ± 0.13; P = 0.0223) and an increase in mean trough levels (1.75 ± 1.01 vs. 2.7 ± 1.28; P = 0.0223) with the same factor consumption. The decrease in ABR was not statistically significant (mean 2.38 ± 1.51 vs. 1.13 ± 1.81; P = 0.0707). The proportion of patients without bleeding was 12.5% for SHL and 62.5% for rFVIIIFc. Conclusion: The switch from SHL treatment to rFVIIIFc was associated with better bleeding control and reduced application number regardless of age, while factor consumption remained unchanged. Benefits were particularly important in children.
Keywords:
haemophilia A – bleeding control – biological half-life – SHL – rFVIIIFc – application number
Sources
1. Peyvandi F, Garagiola I, Guy Y. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016; 388 (10040): 187–197.
2. Smejkal P, Blatný J, Hajšmanová Z, et al. Konsenzuální doporučení Českého národního hemofilického programu (ČNHP) pro diagnostiku a léčbu pacientů s hemofilií, vydání 3., rok 2021. Transfuze Hematol Dnes. 2021; 27 (1): 73–90.
3. Van Vulpen LFD, Holstein K, Martinoli C. Joint disease in haemophilia: Pathophysiology, pain and imaging. Haemophilia. 2018; 24 (Suppl 6): 44–49.
4. Srivastava A, Santangostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020; 26 (Suppl 6): 1–158.
5. Khawaji M, Astermark J, Berntrop E. Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life. Eur J Haematol. 2012; 88 (4): 329–335.
6. Noone D, O‘Mahony B, van Dijk JP, et al. A survey of the outcome of prophylaxis, on-demand or combined treatment in 20-35 year old men with severe haemophilia in four European countries. Haemophilia. 2011; 17 (5): e842–e843.
7. Warren BB, Thornhill D, Stein J, et al. Young adult outcomes of childhood prophylaxis for severe hemophilia A: results of the Joint Outcome Continuation Study. Blood Adv. 2020; 4 (11): 2451–2459.
8. Manco-Johnson MJ, Lundin B, Funk S, et al. Effect of late prophylaxis in hemophilia on joint status: a randomized trial. J Thromb Haemost. 2017; 15 (11): 2115–2124.
9. Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood. 2015; 125 (13): 2038–2044.
10. Mahlangu J, Powell JS, Ragni MV, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014; 123 (3): 317–325.
11. Young G, Mahlangu J, Kulkarni R, et al. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A. J Thromb Haemost. 2015; 13 (6): 967–977.
12. Nolan B, Mahlangu J, Pabinger I, et al. Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: Final results from the ASPIRE extension study. Haemophilia. 2020; 26 (3): 494–502.
13. Königs Ch, Ozelo MC, Dunn A, et al. First study of extended half-life rFVIIIFc in previously untreated patients with hemophilia A: PUPs A-LONG final results. Blood. 2022; 139 (26): 3699–3707.
14. Tagliaferri A, Maticecchia A, Rivolta GF, et al. Optimising prophylaxis outcomes and costs in haemophilia patients switching to recombinant FVIII-Fc: a single-centre real-world experience. Blood Transfus. 2020; 18 (5): 374–385.
15. Holmström M, Olsson E, Astermark J, et al. Real-world prophylactic usage of recombinant factor VIII Fc in Sweden: A report from the Swedish national registry for bleeding disorders. Haemophilia. 2021; 27 (4): e554–e558.
16. Oldenburg J, Goldmann G., Marquardt N, et al. Real-world clinical experience of extended half-life recombinant factor VIII Fc fusion protein (rFVIIIFc) in comparison to conventional factor products in patients with severe hemophilia A. J Curr Med Res Opinion. 2021; 4 (5): 950–960.
17. Ay C, Feistritzer C, Rettl J, et al. Bleeding outcomes and factor utilization after switching to an extended half-life product for prophylaxis in haemophilia A in Austria. Sci Rep. 2021; 11 (1): 12967.
18. Dettoraki A, Michalopoulou A, Mazarakis M, et al. Clinical application of extended half-life factor VIII in children with severe haemophilia A. Haemophilia. 2022; 28 (4): 619–624.
19. Giraud R, Delmotte N, Gensollen S, et al. Recombinant factor VIII Fc fusion protein (rFVIIIFc) in real life: one-year clinical and economic outcomes. Drugs Real World Outcomes. 2021; 8 (4): 527–535.
20. Martin AP, Burge T, Asghar S, et al. Understanding minimum and ideal factor levels for participation in physical activities by people with haemophilia: An expert elicitation exercise. Haemophilia. 2020; 26 (4): 711–717.
21. Von Mackensen S, Harrington C, Tuddenham E, et al. The impact of sport on health status, psychological well-being and physical performance of adults with haemophilia. Haemophilia. 2016; 22 (4): 521–530.
22. Khair K, Holland M, Dodgson S, et al. Fitness enhances psychosocial well-being and self-confidence in young men with hemophilia: Results from Project GYM. Res Pract Thromb Haemost. 2021; 5 (8): e12622.
23. Versloot O, Berntrop E, Petrini P, et al. Sports participation and physical activity in adult Dutch and Swedish patients with severe haemophilia: A comparison between intermediate- and high-dose prophylaxis. Haemophilia. 2019; 25 (2): 244–251.
24. Versloot O, Van Balen EC, Hassan S, et al. Similar sports participation as the general population in Dutch persons with haemophilia; results from a nationwide study. Haemophilia. 2021; 27 (5): 876–885.
25. Saleh M, Alzahrani H, Owaidah T, et al. Impact of extended half-life product versus conventional factor product in children with hemophilia A – findings from a tertiary care centre [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1), Abstrakt PB#1059
26. Kobayashi M, Matsushita T, Nogami K, et al. Real-world effectiveness evaluation of the recombinant factor VIII Fc fusion protein in adolescents and children with hemophilia A in Japan: “Fc Adolescent and Children Treatment” Study (FACTs) part 1 interim analysis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1), Abstrakt PB#0879
27. Moretti L, Bizzoca D, Buono C, et al. Sports and children with hemophilia: current trends. Children (Basel). 2021; 8 (11): 1064.
28. Den Ujil EM, Mauser Bunschoten EP, Roosendaal G, et al. Clinical severity of haemophilia A: does the classification of the 1950s still stand? Haemophilia. 2011; 17 (6): 849–853.
29. Valentino LA, Pipe SW, Collins PW, et al. Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis. Haemophilia. 2016; 22 (4): 514–520.
30. Versloot O, Iserman E, Chelle P, et al. Terminal half-life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database. J Throm Haemost. 2021; 19 (8): 1896–1906.
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