Budget impact analysis of extended half-life recombinant factor IX (rFIXFc) in the treatment of haemophilia B
Introduction: Prophylaxis with factor IX (FIX) concentrates, produced by recombinant DNA technology (rFIX) or human plasma-derived concentrates, is the treatment of choice for haemophilia B (HB); rFIX covalently fused to the Fc domain of human immunoglobulin G1 (rFIXFc) allows for prophylaxis/treatment with one infusion every 7-14 days. The purpose of this study is to quantify the financial impact of prophylaxis with rFIXFc vs. other approved rFIX and reimbursed for treatment of HB in Italy.
Methods: The number of patients was estimated according to Italian epidemiological data and use of rFIX. Dose and frequency of administration used for weekly prophylaxis were those recommended in the Summary of Product Characteristics (SPC), while clinical trials and literature data were used to calculate bleeding rates and management. Drug costs were calculated using regional ex-factory net prices. In the model, a reference scenario (Reference) vs. an alternative scenario (Alternative) were created to account for introduction of rFIXFc, estimating an increasing trend of the market share of rFIXFc in a 3-year timeframe. The analysis was developed in the perspective of the National Health Service and included healthcare costs related to rFIX for prophylaxis and resolution of bleeding events.
Results: The model estimated an overall cumulative expenditure (years 1-3) of €209,453,646 for the Reference and €207,465,568 for Alternative scenarios, with calculated cumulative savings of €1,988,068.
Conclusions: The increasing use of rFIXFc as a substitute for other rFIX concentrates in the treatment of HB can represent a financially viable choice for the Italian National Health Service while ensuring effective control of bleeding.
World Federation of Haemophilia. Guidelines for the management of Haemophilia. 2nd ed. 2013. Available at: https://www1.wfh.org/publications/files/pdf-1472.pdf accessed 12/06/2020.
ORPHANET. Emofilia B. Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=IT&Expert=98879 accessed 12/06/20
Abbonizio F, Hassan HJ, Riccioni R, Arcieri R, Associazione Italiana Centri Emofilia (AICE), Giampaolo. Registro Nazionale delle Coagulopatie Congenite. Rapporto 2017. Roma: Istituto Superiore di Sanità 2019 (Rapporti ISTISAN 19/8).
Budde U, Drewke E. Von Willebrand factor multimers in virus-inactivated plasmas and F VIII concentrates. Beitr Infusionsther Transfusionsmed 1994;32:408-414.
Chin S, Williams B, Gottlieb P, et al. Virucidal short wavelength ultraviolet light treatment of plasma and factor VIII concentrate: protection of proteins by antioxidants. Blood 1995 Dec 1;86(11):4331-4336.
Chuansumrit A, Isarangkura P, Chantanakajornfung A, et al. The efficacy and safety of lyophilized cryoprecipitate in haemophilia A. J Med Assoc Thai 1999 Nov;82 Suppl 1:S69-S73.
El-Ekiaby M, Sayed MA, Caron C, et al. Solvent-detergent filtered (S/D-F) fresh frozen plasma and cryoprecipitate minipools prepared in a newly designed integral disposable processing bag system. Transfus Med 2010 Feb;20(1):48-61.
Franchini M, Rossetti G, Tagliaferri A, et al. Dental procedures in adult patients with hereditary bleeding disorders: 10 years experience in three Italian haemophilia centers. Haemophilia 2005;11:504-509.
Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 1997 Oct 1;90(7):2515-2521.
World Federation of Hemophilia. What is prophylaxis. Last Updated December 2014. Available at: https://elearning.wfh.org/elearning-centres/prophylaxis/#what_is_prophylaxis accessed 12/06/2020.
Roth DA, Kessler CM, Pasi KJ, Rup B, Courter SG, Tubridy KL. Human recombinant factor IX: safety and efficacy studies in haemophilia B patients previously treated with plasma-derived factor IX concentrates. Blood 2001 Dec 15;98(13):3600-3606.
Windyga J, Lissitchkov T, Stasyshyn O, et al. Pharmacokinetics, efficacy and safety of BAX326, a novel recombinant factor IX: a prospective, controlled, multicentre phase I/III study in previously treated patients with severe (FIX level <1%) or moderately severe (FIX level =2%) haemophilia B. Haemophilia 2014 Jan;20(1):15-24.
De Moerloose P, Urbancik W, Van Den Berg HM, Richards M. A survey of adherence to haemophilia therapy in six European countries: results and recommendations. Haemophilia 2008 Sep;14(5):931-938.
du Treil S, Rice J, Leissinger CA. Quantifying adherence to treatment and its relationship to quality of life in a well-characterized haemophilia population. Haemophilia 2007 Sep;13(5):493-501.
Duncan N, Kronenberger W, Roberson C, Shapiro A. VERITAS-Pro: a new measure of adherence to prophylactic regimens in haemophilia. Haemophilia 2010 Mar;16(2):247-255.
Geraghty S, Dunkley T, Harrington C, Lindvall K, Maahs J, Sek J. Practice patterns in haemophilia A therapy – global progress towards optimal care. Haemophilia 2006 Jan;12(1):75-81.
Iorio A, Krishnan S, Myren KJ, et al. Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption. J Med Econ 2017 Apr;20(4):337-344.
Schrijvers LH, Uitslager N, Schuurmans MJ, Fischer K. Barriers and motivators of adherence to prophylactic treatment in haemophilia: a systematic review. Haemophilia 2013 May;19(3):355-361.
Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with prophylaxis therapy in haemophilia. Haemophilia 2001 Jul;7(4):392-396.
Krishnan S, Vietri J, Furlan R, Duncan N. Adherence to prophylaxis is associated with better outcomes in moderate and severe haemophilia: results of a patient survey. Haemophilia 2015 Jan;21(1):64-70.
McLaughlin JM, Witkop ML, Lambing A, Anderson TL, Munn J, Tortella B. Better adherence to prescribed treatment regimen is related to less chronic pain among adolescents and young adults with moderate or severe haemophilia. Haemophilia 2014 Jul;20(4):506-512.
Schrijvers LH, Kars MC, Beijlevelt-van der Zande M, Peters M, Schuurmans MJ, Fischer K. Unravelling adherence to prophylaxis in haemophilia: a patients’ perspective. Haemophilia 2015 Sep;21(5):612-621.
Fischer K, Kulkarni R, Nolan B, et al. Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study. Lancet Haematol 2017 Feb;4(2):e75-e82.
Kenet G, Chambost H, Male C, et al. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children. Results of a phase 3 trial. Thromb Haemost 2016 Sep 27;116(4):659-668.
Powell JS, Pasi KJ, Ragni MV, et al. Phase 3 study of recombinant factor IX Fc fusion protein in haemophilia B. N Engl J Med 2013 Dec 12;369(24):2313-2323.
Santagostino E, Martinowitz U, Lissitchkov T, et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in haemophilia B: results of a phase 3 trial. Blood 2016 Apr 7;127(14):1761-1769.
European Medicine Agency (EMA). Alprolix: EPAR – Product Information. Last updated 10/04/2019. Available at: https://www.ema.europa.eu/en/documents/product-information/alprolix-epar-product-information_it.pdf accessed 12/06/2020.
European Medicine Agency (EMA). Idelvion: EPAR – Product Information. Last updated 28/05/2020. Available at: https://www.ema.europa.eu/en/documents/product-information/idelvion-epar-product-information_it.pdf accessed 12/06/2020.
European Medicine Agency (EMA). Rixubis: EPAR – Product Information. Last updated 16/03/2020. Available at: https://www.ema.europa.eu/en/documents/product-information/rixubis-epar-product-information_it.pdf accessed 12/06/2020.
European Medicine Agency (EMA). Benefix: EPAR – Product Information. Last updated 18/01/2019. Available at: https://www.ema.europa.eu/en/documents/product-information/benefix-epar-product-information_it.pdf accessed 12/06/2020.
Osservatorio Nazionale sull’impiego dei Medicinali. L’uso dei farmaci in Italia. Rapporto Nazionale Anno 2018. Roma: Agenzia Italiana del Farmaco 2019.
Gazzetta Ufficiale della Repubblica Italiana. Available at: http://22.214.171.124/gazzettaufficiale.biz/emittenti/elencoEmittente9.htm accessed 12/06/2020.
Istituto Nazionale di Statistica (ISTAT). Previsioni della Popolazione anno 2017-2065. Available at: http://demo.istat.it/ accessed 12/06/2020.
Pradelli L, Villa S, Castaman G. Albutrepenonacog alfa (Idelvion®) for the treatment of Italian patients with haemophilia B: a budget impact model. Farmeconomia. Health Econ Therapeut Pathways 2018;19(1):1-10.
Valentino LA, Rusen L, Elezovic I, Smith LM, Korth-Bradley JM, Rendo P. Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects. Haemophilia 2014 May;20(3):398-406.
European Medicine Agency (EMA). Rixubis: EPAR European Public Assessment Report. Last updated 16/03/2020. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/rixubis#product-information-section accessed 12/06/2020.
Prezzi da aggiudicazione da Gara Regionale: Piemonte, Veneto, Toscana, Lazio, Campania, Puglia e Sicilia. Data on file. 2019.
Kavakli K, Smith L, Kuliczkowski K, et al. Once-weekly prophylactic treatment vs. on-demand treatment with nonacog alfa in patients with moderately severe to severe haemophilia B. Haemophilia 2016 May;22(3):381-388.
Furlan R, Krishnan S, Vietri J. Patient and parent preferences for characteristics of prophylactic treatment in haemophilia. Patient Prefer Adherence 2015;9:1687-1694.
Zhang Y, Roberts J, Bensen-Kennedy D, et al. Population pharmacokinetics of a new long-acting recombinant coagulation factor IX albumin fusion protein for patients with severe haemophilia B. J Thromb Haemost 2016 Nov;14(11):2132-2140.
Kodra Y, Cavazza M, Schieppati A, et al. The social burden and quality of life of patients with haemophilia in Italy. Blood Transfus 2014 Apr;12 Suppl 3:s567-s575.
Malec LM, Croteau SE, Callaghan M, Matino D, Friedman KD, Sidonio RF, Jr. Spontaneous bleeding and poor bleeding response with extended half-life factor IX products: a survey of select US and Canadian haemophilia treatment centers. Blood 2019 Nov 13;134(Suppl 1):2407.
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