Costs of the management of hemophilia A with inhibitors in Spain
DOI:
https://doi.org/10.33393/grhta.2021.2234Keywords:
Activated prothrombin complex concentrate, Costs, Emicizumab, Hemophilia A, Recombinant factor VIIaAbstract
Introduction: Emicizumab is a first-in-class monoclonal antibody, recently authorized for the treatment of hemophilia A with inhibitors. This study aims to estimate the direct and indirect costs of the management of hemophilia A with inhibitors, in adult and pediatric patients, including the prophylaxis with emicizumab.
Methods: We calculated the costs of the on-demand and prophylactic treatments with bypassing agents (activated prothrombin complex concentrate and recombinant activated factor VII) and the emicizumab prophylaxis, from the societal perspective, over 1 year. The study considered direct healthcare costs (drugs, visits, tests, and hospitalizations), direct non-healthcare costs (informal caregivers), and indirect costs (productivity loss). Data were obtained from a literature review and were validated by an expert group. Costs were expressed in 2019 euros.
Results: Our results showed that the annual costs of the prophylactic treatment per patient varied between €543,062.99 and €821,415.77 for adults, and €182,764.43 and €319,826.59 for children, while on-demand treatment was €532,706.84 and €789,341.91 in adults, and €167,523.05 and €238,304.71 in pediatric patients. In relation to other prophylactic therapies, emicizumab showed the lowest costs, with up to a 34% and 43% reduction in the management cost of adult and pediatric patients, respectively. It reduced the bleeding events and administration costs, as this drug is less frequently administered by subcutaneous route. Emicizumab prophylaxis also decreased the cost of other healthcare resources such as visits, tests, and hospitalizations, as well as indirect costs.
Conclusion: In comparison to prophylaxis with bypassing agents, emicizumab reduced direct and indirect costs, resulting in cost savings for the National Health System and society.
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References
Ministerio de Sanidad, Servicios Sociales e Igualdad: Hemofilia. https://www.mscbs.gob.es/profesionales/saludPublica/medicinaTransfusional/publicaciones/docs/Hemofilia_AspectosOrganizativos.pdf. Accessed May 8, 2019.
Grupo de hemostasia y trombosis: Guía asistencial de hemofilia en Castilla y León. http://www.sclhh.org/docs/pdf/consenso/Hemofilia%20Guia%20Asistencial%20v3.pdf. Accessed May 8, 2019.
Aznar JA, Altisent C, Álvarez-Román MT, Bonanad S, Mingot-Castellano ME, López MF. Moderate and severe haemophilia in Spain: an epidemiological update. Haemophilia. 2018;24(3):e136-e139. https://doi.org/10.1111/hae.13462 PMID:29578308
Federación Española de Hemofilia (FEDHEMO). http://fedhemo.com/inhibidores/. Accessed June 3, 2020.
Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): Informe de Posicionamiento Terapéutico de emicizumab (Hemlibra®) en hemofilia A con inhibidores del factor VIII. https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/IPT-emicizumab-Hemlibra-hemofilia-A.pdf (2019). Accessed June 20, 2019.
López-Fernández MF, Altisent Roca C, Álvarez-Román MT, et al. Spanish Consensus Guidelines on prophylaxis with bypassing agents in patients with haemophilia and inhibitors. Thromb Haemost. 2016;115(5):872-895. https://doi.org/10.1160/TH15-07-0568 PMID:26842562
Villarrubia R, Oyagüez I, Álvarez-Román MT, Mingot-Castellano ME, Parra R, Casado MA. Cost analysis of prophylaxis with activated prothrombin complex concentrate vs. on-demand therapy with activated factor VII in severe haemophilia A patients with inhibitors, in Spain. Haemophilia. 2015;21(3):320-329. https://doi.org/10.1111/hae.12681 PMID:25855214
Mingot-Castellano ME, Álvarez-Román MT, López-Fernández MF, et al. Spanish consensus guidelines on prophylaxis with bypassing agents for surgery in patients with haemophilia and inhibitors. Eur J Haematol. 2016;96(5):461-474. https://doi.org/10.1111/ejh.12730PMID:26714021
Leissinger CA. Prevention of bleeds in hemophilia patients with inhibitors: emerging data and clinical direction. Am J Hematol. 2004;77(2):187-193. https://doi.org/10.1002/ajh.20162PMID:15389908
Hay CR, Ludlam CA, Colvin BT, et al; UK Haemophilia Centre Directors Organisation. Factor VIII inhibitors in mild and moderate-severity haemophilia A. Thromb Haemost. 1998;79(4):762-766. https://doi.org/10.1055/s-0037-1615061 PMID:9569189
Leissinger C, Cooper DL, Solem CT; HTRS Investigators. Assessing the impact of age, race, ethnicity and inhibitor status on functional limitations of patients with severe and moderately severe haemophilia A. Haemophilia. 2011;17(6):884-889. https://doi.org/10.1111/j.1365-2516.2011.02509.x PMID:21447095
Walsh CE, Soucie JM, Miller CH; United States Hemophilia Treatment Center Network. Impact of inhibitors on hemophilia A mortality in the United States. Am J Hematol. 2015;90(5):400-405. https://doi.org/10.1002/ajh.23957 PMID:25616111
European Medicines Agency (EMA). First-in-class medicine to prevent bleeding in haemophilia A patients with inhibitors. https://www.ema.europa.eu/en/news/first-class-medicine-prevent-bleeding-haemophilia-patients-inhibitors. Accessed March 12, 2020.
European Medicine Agency: Hemlibra. Ficha técnica o resumen de las características del producto. https://www.ema.europa.eu/en/medicines/human/EPAR/hemlibra. Accessed June 25, 2019.
Álvarez-Román MT, Cuervo-Arango I, Pérez-Santamarina R, et al. Determining the value contribution of emicizumab (Hemlibra®) for the prophylaxis of haemophilia A with inhibitors in Spain by multi-criteria decision analysis. Glob Reg Health Technol Assess. 2019;1-8. https://doi.org/10.1177/2284240319880534
Skinner M. Emicizumab prophylaxis improves long-term health-related quality of life (HRQoL) in Persons with Haemophilia A (PwHA) with and without inhibitors: update from the HAVEN 3 and HAVEN 4 studies. https://academy.isth.org/isth/2019/melbourne/263893/mark.skinner.emicizumab.prophylaxis.improves.long-term.health-related.quality.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D2%2Asearch%3Dhaven. Accessed February 25, 2020.
Jiménez-Yuste V, Álvarez Román MT, Mingot-Castellano ME, Fernández Mosteirin N, Mareque M, Oyagüez I. Análisis de costes del tratamiento para pacientes con hemofilia A con inhibidor en España. PharmacoEcon Span Res Artic. 2018;15(1-4):25-34. https://doi.org/10.1007/s40277-018-0080-y
Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): CIMA. Feiba 25 U/mL polvo y disolvente para solución para perfusión. Ficha técnica o resumen de las características del producto. https://cima.aemps.es/cima/dochtml/ft/80118/FT_80118.html. Accessed May 28, 2019.
Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): CIMA. NovoSeven. https://cima.aemps.es/cima/publico/detalle.html?nregistro=196006008. Accessed November 6, 2019.
Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809-818. https://doi.org/10.1056/NEJMoa1703068PMID:28691557
Young G, Oldenburg J, Liesner R, et al. HAVEN 2: efficacy, safety and pharmacokinetics of once-weekly prophylactic emicizumab (ACE910) in pediatric patients (<12 years) with hemophilia A with inhibitors: interim analysis of single-arm, multicenter, open-label, phase 3 study. American Society of Hematology. 60th ASH Annual Meeting and Exposition; 2018 Dec 1; San Diego, California.
Mahlangu J, Oldenburg J, Callaghan MU, et al. Bleeding events and safety outcomes in persons with haemophilia A with inhibitors: a prospective, multi-centre, non-interventional study. Haemophilia. 2018;24(6):921-929. https://doi.org/10.1111/hae.13612 PMID:30295389
Dimichele D, Négrier C. A retrospective postlicensure survey of FEIBA efficacy and safety. Haemophilia. 2006 Jul;12(4):352-362. https://doi.org/10.1111/j.1365-2516.2006.01284.x. PMID: 16834734.
National Statistics Institute. Working market. https://www.ine.es/dyngs/INEbase/categoria.htm?c=Estadistica_P&cid=1254735976594. Accessed November 4, 2019.
Aznar JA, Lucía F, Abad-Franch L, et al. Haemophilia in Spain. Haemophilia. 2009;15(3):665-675. https://doi.org/10.1111/j.1365-2516.2009.02001.x PMID:19432921
Consejo General de Colegios Oficiales de Farmacéuticos: Bot Plus 2.0 Base de Datos de Medicamentos. https://botplusweb.portalfarma.com/botplus.aspx. Accessed February 27, 2019.
Ministerio de Sanidad: Listado de Medicamentos afectados por las deducciones del RD 8/2010. http://www.mscbs.gob.es/en/profesionales/farmacia/notasInfor.htm. Accessed February 27, 2019.
Median value of the unit costs for Autonomous Communities (2019)
Ministerio de Sanidad, Consumo y Bienestar Social. Subdirección General de Información Sanitaria. Registro de Actividad de Atención Especializada – RAE-CMBD. https://pestadistico.inteligenciadegestion.mscbs.es/PUBLICOSNS. Accessed August 29, 2019.
Bastida JL, Linertová R, Aguilar PS, Hens Pérez M, Posada de la Paz M, Oliva Moreno J. Los costes socioeconómicos y la calidad de vida relacionada con la salud en pacientes con enfermedades raras en España. IMSERSO. 114 (2012). https://enfermedades-raras.org/images/pdf/los_costes_socioeconomicos_y_la_calidad_de_vida.pdf. Accessed March 5, 2020.
van den Berg B, Brouwer WBF, Koopmanschap MA. Economic valuation of informal care. An overview of methods and applications. Eur J Health Econ. 2004;5(1):36-45. https://doi.org/10.1007/s10198-003-0189-y PMID:15452763
Zhou Z-Y, Hay JW. Efficacy of bypassing agents in patients with hemophilia and inhibitors: a systematic review and meta-analysis. Clin Ther. 2012;34(2):434-445. https://doi.org/10.1016/j.clinthera.2012.01.001 PMID:22285208
O’Hara J, Hughes D, Camp C, Burke T, Carroll L, Diego DG. The cost of severe haemophilia in Europe: the CHESS study. Orphanet J Rare Dis. 2017;12(1):106. https://doi.org/10.1186/s13023-017-0660-y PMID:28569181
Oak B, Nambiar S, Springs S, Eguale T. A comparison of prophylactic versus on-demand treatment regimens of coagulation factor VIII for bleeding and joint outcomes in Hemophilia A patients without inhibitors: a systematic review and meta-analysis. Value Health. 2018;21:S247. https://doi.org/10.1016/j.jval.2018.04.1672
Nugent D, O’Mahony B, Dolan G; International Haemophilia Access Strategy Council. Value of prophylaxis vs on-demand treatment: application of a value framework in hemophilia. Haemophilia. 2018;24(5):755-765. https://doi.org/10.1111/hae.13589 PMID:30088692
Castaman G, Linari S. Prophylactic versus on-demand treatments for hemophilia: advantages and drawbacks. Expert Rev Hematol. 2018;11(7):567-576. https://doi.org/10.1080/17474086.2018.1486704 PMID:29886751
Earnshaw SR, Graham CN, McDade CL, Spears JB, Kessler CM. Factor VIII alloantibody inhibitors: cost analysis of immune tolerance induction vs. prophylaxis and on-demand with bypass treatment. Haemophilia. 2015;21(3):310-319. https://doi.org/10.1111/hae.12621PMID:25688580
Cortesi PA, Castaman G, Trifirò G, et al. Cost-effectiveness and budget impact of emicizumab prophylaxis in haemophilia A patients with inhibitors. Thromb Haemost. 2020;120(2):216-228. https://doi.org/10.1055/s-0039-3401822 PMID:31887777
Patel AM, Corman SL, Chaplin S, Raimundo K, Sidonio RF. Economic impact model of delayed inhibitor development in patients with hemophilia a receiving emicizumab for the prevention of bleeding events. J Med Econ. 2019;22(12):1328-1337. https://doi.org/10.1080/13696998.2019.1669614 PMID:31530050
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Accepted 2021-02-24
Published 2021-04-01
