Blood Res.  2024;59:30. 10.1007/s44313-024-00034-6.

Real‑world insights into the management of hemophilia A in Italy: treatment patterns and healthcare resource utilization

• Perrone V
• Leogrande M
• Cappuccilli M
• Esposti L

• KMID: 2562534
• DOI: http://doi.org/10.1007/s44313-024-00034-6

Abstract

Purpose
This real-world analysis described the Hemophilia A (HA) population in Italy, evaluating drug utilization and consumption of factor VIII (FVIII) products of patients under prophylaxis and on-demand therapy.
Methods
From Jan-2017 to Jun-2022, male patients with HA were identified through prescriptions of FVIII products [extended half-life FVIII, standard half-life recombinant FVIII, and plasma-derived FVIII (EHL FVIII, SHL rFVIII, and pdFVIII, respectively)], or emicizumab or FVIII plus von Willebrand factor or HA-related hospitalization using administrative flows of Italian healthcare entities. Patients on treatment with FVIII products during 2021–2022 were stratified by treatment regimen (prophylaxis/on-demand). The mean annual consumption expressed in International Units (IU) of EHL FVIII and SHL FVIII in patients treated during 2021–2022 having at least 12-month follow-up were assessed.
Results
Among included HA patients, 145 (39.5%) received EHL FVIII and 222 (60.5%) SHL FVIII. Of 165 patients on prophylaxis, 105 (64%) received an EHL FVIII and 60 (36%) an SHL FVIII. The mean annual consumption of FVIII was 336,700 IU (median 319,000 IU) for EHL FVIII and 440,267 IU (median 360,500 IU) for SHL FVIII. Specifically, for patients on EHL FVIII, the most common drugs were efmoroctocog alfa (N = 51) and damoctocog alfa pegol (N = 50), followed by turoctocog alfa pegol (N = 25) and rurioctocog alfa pegol (N = 19). Of 702 HA patients initially treated with FVIII products, 74 (10.5%) switched to emicizumab during follow-up.
Conclusion
These findings revealed an extensive use of EHL FVIII products, suggesting growing efforts from clinicians to optimize prophylactic strategies and achieve better bleeding protection.

Keyword

Healthcare resource utilization; Hemophilia A; Monoclonal antibodies; Plasma-derived FVIII; Treatment patterns

Figure

• 

  Fig. 1 Scheme for patients’ selection

• 

  Fig. 2 Distribution of prophylaxis treatments according to the different types of FVIII

Reference

1. Berntorp E, Fischer K, Hart DP, et al. 2021; Haemophilia. Nat Rev Dis Primers. 7(1):45. https://doi.org/10.1038/s41572-021-00278-x. DOI: 10.1038/s41572-021-00278-x.

2. Salen P, Babiker HM. 2023. Hemophilia. StatPearls. Stat-Pearls Publishing;Treasure Island (FL): DOI: 10.7759/cureus.40822.

3. World Federation of Hemophilia Report on the Annual Global Survey 2021. Available at: https://www1.wfh.org/publications/files/pdf-2324.pdf. last accessed 07 March, 2024.

4. Castaman G, Matino D. 2019; Hemophilia A and B: molecular and clinical similarities and differences. Haematologica. 104(9):1702–9. https://doi.org/10.3324/haematol.2019.221093. DOI: 10.3324/haematol.2019.221093. PMID: 1ffd220d3e6040df86a8b429f58f8f58.

5. Factor VIII Concentrates. 2009; Factor VIII/von Willebrand factor concentrates, factor IX concentrates, activated prothrombin complex concentrates. Transfus Med Hemother. 36(6):409–18. DOI: 10.1159/000268062.

6. Giampaolo A, Abbonizio F, Arcieri R, Hassan HJ. 2017; Italian registry of congenital bleeding disorders. J Clin Med. 6(3):34. https://doi.org/10.3390/jcm6030034. DOI: 10.3390/jcm6030034. PMID: 28335488. PMCID: PMC5373003.

7. Italian National Institute of Health (ISS). National Registry of congenital bleeding disorders. Report 2020. Available at: https://www.iss.it/documents/20126/6682486/22-38+web.pdf/fe31bd00-c203-c009-adc6-5e49620ba148?t=1678781150708. last accessed 07 March 2024.

8. Centers for Disease Control and Prevention. Hemophilia. Available at: https://www.cdc.gov/ncbddd/hemophilia/data.html. last accessed 07 March 2024.

9. Mehta P, Reddivari AKR. 2024. Jan-. Hemophilia. StatPearls. StatPearls Publishing;Treasure Island (FL): Available from: https://www.ncbi.nlm.nih.gov/books/NBK551607/. Updated 2023 Jun 5.

10. Franchini M, Mannucci PM. 2013; Acquired haemophilia A: a 2013 update. Thromb Haemost. 110(6):1114–20. https://doi.org/10.1160/TH13-05-0363. DOI: 10.1160/TH13-05-0363. PMID: 24008306.

11. Aledort L, Mannucci PM, Schramm W, Tarantino M. 2019; Factor VIII replacement is still the standard of care in haemophilia A. Blood Transfus. 17(6):479–86. https://doi.org/10.2450/2019.0211-19. DOI: 10.2450/2019.0211-19. PMID: 31846611. PMCID: PMC6917528.

12. Gomperts E, Lundblad R, Adamson R. 1992; The manufacturing process of recombinant factor VIII, recombinate. Transfus Med Rev. 6(4):247–51. https://doi.org/10.1016/s0887-7963(92)70175-8. DOI: 10.1016/S0887-7963(92)70175-8.

13. Mannucci PM. 2020; Hemophilia therapy: the future has begun. Haematologica. 105(3):545–53. https://doi.org/10.3324/haematol.2019.232132. DOI: 10.3324/haematol.2019.232132. PMID: 32060150. PMCID: PMC7049365. PMID: 9ae3d0c2c2ad465f8bd616467dff05bc.

14. Cortesi PA, Giampaolo A, Abbonizio F, et al. 2021; Variability of treatment modalities and intensity in patients with severe haemophilia A on prophylaxis: Results from the Italian national registry. Eur J Haematol. 107(4):408–15. https://doi.org/10.1111/ejh.13676. DOI: 10.1111/ejh.13676.

15. Srivastava A, Santagostino E, Dougall A, et al. 2020; WFH Guidelines for the Management of Hemophilia, 3rd edition [published correction appears in Haemophilia. 2021 27(4):699]. Haemophilia. 26 Suppl 6:1–158. https://doi.org/10.1111/hae.14046. DOI: 10.1111/hae.14046.

16. Peyvandi F, Kavakli K, El-Beshlawy A, Rangarajan S. 2022; Management of haemophilia a with inhibitors: a regional cross-talk. Haemophilia. 28(6):950–61. https://doi.org/10.1111/hae.14638. DOI: 10.1111/hae.14638.

17. FDA Approves Hemlibra (emicizumab-kxwh) for Hemophilia A with Inhibitors. Available at: https://www.drugs.com/newdrugs/fda-approves-hemlibra-emicizumab-kxwh-hemophilia-inhibitors-4639.html. last accessed 07 March 2024.

18. European Medicines Agency (EMA). Hemlibra (emicizumab). Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/hemlibra. last accessed 07 March 2024.

19. Agenzia Italiana del Farmac (AIFA). Determina 21 febbraio 2020 Regime di rimborsabilita' e prezzo a seguito di nuove indicazioni terapeutiche del medicinale per uso umano «Hemlibra». (Determina n. 206/2020).). Available at: https://www.gazzettauf​ficiale.it/eli/id/2020/03/18/20A01588/SG. last accessed 07 March 2024.

20. Kiialainen A, Niggli M, Kempton CL, et al. 2022; Effect of emicizumab prophylaxis on bone and joint health markers in people with haemophilia A without factor VIII inhibitors in the HAVEN 3 study. Haemophilia. 28(6):1033–43. https://doi.org/10.1111/hae.14642. DOI: 10.1111/hae.14642.

21. Charlson ME, Pompei P, Ales KL, MacKenzie CR. 1987; A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 40(5):373–83. https://doi.org/10.1016/0021-9681(87)90171-8. DOI: 10.1016/0021-9681(87)90171-8.

22. Kempton CL, Makris M, Holme PA. 2021; Management of comorbidities in haemophilia. Haemophilia. 27(Suppl 3):37–45. https://doi.org/10.1111/hae.14013. DOI: 10.1111/hae.14013.

23. Versloot O, Iserman E, Chelle P, Germini F, Edginton AN, Schutgens REG, Iorio A, Fischer K. Pharmacokinetic (PK) Expert Working Group of the International Prophylaxis Study Group (IPSG). 2021; Terminal half-life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database. J Thromb Haemost. 19(8):1896–906. https://doi.org/10.1111/jth.15395. DOI: 10.1111/jth.15395.

24. Cortesi PA, Di Minno G, Zanon E, et al. 2022; Real-world clinical outcomes and replacement factor VIII consumption in patients with Haemophilia A in Italy: a comparison between prophylaxis pre and post Octocog Alfa (BAY 81-8973). J Clin Med. 11(12):3434. https://doi.org/10.3390/jcm11123434. DOI: 10.3390/jcm11123434. PMID: 35743504. PMCID: PMC9224869.

25. Nolan B, Mahlangu J, Pabinger I, et al. 2020; Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: Final results from the ASPIRE extension study. Haemophilia. 26(3):494–502. https://doi.org/10.1111/hae.13953. DOI: 10.1111/hae.13953. PMID: 32227570. PMCID: PMC7384031.

26. Blatný J, Nielsen EM, Reitzel SB, et al. 2023; Real-world evidence on efmoroctocog alfa in patients with haemophilia A: A systematic literature review of treatment experience in Europe. Haemophilia. 29(4):963–74. https://doi.org/10.1111/hae.14797. DOI: 10.1111/hae.14797.

27. Frampton JE. 2021; Efmoroctocog Alfa: a review in Haemophilia A. Drugs. 81(17):2035–46. https://doi.org/10.1007/s40265-021-01615-w.Epub2021Nov7.Erratumin:Drugs.2022Jan;82(1):95. DOI: 10.1007/s40265-021-01615-w. PMID: 34743314. PMCID: PMC8636404.

28. Escobar M, Agrawal N, Chatterjee S, et al. 2023; Impact of switching prophylaxis treatment from factor VIII to emicizumab in hemophilia A patients without inhibitors. J Med Econ. 26(1):574–80. https://doi.org/10.1080/13696998.2023.2196922. DOI: 10.1080/13696998.2023.2196922.

29. Cafuir L, Estrin A, Chen E, et al. 2022; Early real-world experience with emicizumab and concomitant factor VIII replacement products in adult males with Hemophilia A without inhibitors. J Med Econ. 25(1):984–92. https://doi.org/10.1080/13696998.2022.2102779. DOI: 10.1080/13696998.2022.2102779.

30. Italian Association of Haemophilia Centres (AICE). Gestione del paziente con Emofilia A grave senza inibitore in profilassi con Emicizumab con particolare riferimento alle condizioni di emergenza/urgenza. Available at: https://aiceonline.org/wp-content/uploads/2020/10/Emicizuab-noninibitore-settembre-2020.pdf. last accessed 07 March 2024.