Extended Half-life rFVIII for the Treatment of Hemophilia A: Drugs Consumption and Patients’ Perspective
DOI:
https://doi.org/10.7175/fe.v21i1.1472Keywords:
Hemophilia A, Extended half-life, FVIII, ProphylaxisAbstract
Prophylaxis is recognized as the most effective treatment regimen for patients with severe hemophilia A. Prophylaxis with standard half-life (SHL) FVIII products requires frequent intravenous administrations, at least two-three times per week. Frequency of injections is reported as one of the major obstacles to adherence to treatment and caused impairment in quality of life (QoL) and possible clinical implications. The extended half-life (EHL) rFVIII products recently reimbursed by Italian National Health Service (NHS), give the possibility of prophylactic dosage regimens characterized by reduced administration frequency with the potential to increase adherence to therapy and to improve QoL and clinical outcomes. Based on the approved dosing regimens the minimum and maximum number of administrations per year and the annual consumption for the marketed EHL rFVIII products were estimated. Compared to Adynovi® and Elocta®, Jivi® is the drug associated with the lowest number of administrations per year while versus Esperoct® is associated to a slightly higher maximum number of administrations per year. Furthermore, Jivi® has an annual mean consumption per kg lower than Adynovi®, Elocta® and Esperoct® (-24%, -27% and -22%, respectively). The contemporary reduction of number of injections per year and the lower annual mean consumption (IU) represent important benefits for the patient. From the economic point of view, at the prices published in Italian Official Journal, Jivi® weighted average annual expenditure per patient is 26% lower than Adynovi® and 29% lower than Elocta® and a saving is possible even considering a 10% increase in Jivi®’s price per IU versus comparators. Among the EHL rFVIII concentrates Jivi® appears to be more suitable to cover patients’ needs due to the possibility to adopt different dosage regimens (up to every 7 days) and is associated with the lowest average annual consumption per patient allowing a more predictable budget forecast and overall reducing the NHS expenditure.
References
Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al; Treatment Guidelines Working Group on Behalf of The World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophilia 2013; 19: e1-47; https://doi.org/10.1111/j.1365-2516.2012.02909.x
Drelich DA. Hemophilia A. Medscape, 2019. Available at https://emedicine.medscape.com/article/779322-overview#a1 (last accessed January 2020)
Rocino A, Coppola A, Franchini M, et al. Principles of treatment and update of recommendations for the management of haemophilia and congenital bleeding disorders in Italy. Blood Transfus 2014; 12: 575-98; https://doi.org/10.2450/2014.0223-14
Colvin BT, Astermark J, Fischer K, et al; Inter Disciplinary Working Group. European principles of haemophilia care. Haemophilia 2008; 14: 361-74; https://doi.org/10.1111/j.1365-2516.2007.01625.x
Berntorp E, Boulyjenkov V, Brettler D, et al. Modern treatment of haemophilia. Bull World Health Organ 1995; 73: 691-701
Mancuso ME, Santagostino E. Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates. J Clin Med 2017; 6: E39; https://doi.org/10.3390/jcm6040039
Balkaransingh P, Young G. Novel therapies and current clinical progress in hemophilia A. Ther Adv Hematol 2018; 9: 49-61; https://doi.org/10.1177/2040620717746312
Schrijvers LH, Uitslager N, Schuurmans MJ, et al. Barriers and motivators of adherence to prophylactic treatment in haemophilia: a systematic review. Haemophilia 2013; 19: 355-61; https://doi.org/10.1111/hae.12079
Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with prophylaxis therapy in haemophilia. Haemophilia 2001; 7: 392-6; https://doi.org/10.1046/j.1365-2516.2001.00534.x
Richards M, Altisent C, Batorova A et al. Should prophylaxis be used in adolescent and adult patients with severe haemophilia? An European survey of practice and out- come data. Haemophilia 2007; 13: 473-9; https://doi.org/10.1111/j.1365-2516.2007.01478.x.
Jimenez-Yuste V, Auerswald G, Benson G, et al. Achieving and maintaining an optimal trough level for prophylaxis in haemophilia: the past, the present and the future. Blood Transfus 2014; 12: 314–9; https://doi.org/10.2450/2014.0298-13
Von Mackensen S, Kalnins W, Krucker J, et al. Haemophilia patients’ unmet needs and their expectations of the new extended half-life factor concentrates. Haemophilia 2017; 23: 566-74; https://doi.org/10.1111/hae.13221
Mahlangu J, Young G, Hermans C, et al. Defining extended half-life rFVIII-A critical review of the evidence. Haemophilia 2018; 24: 348-58; https://doi.org/10.1111/hae.13438
Lambert T, Benson G, Dolan G, et al. Practical aspects of extended half-life products for the treatment of haemophilia. Ther Adv Hematol 2018; 9: 295-308; https://doi.org/10.1177/2040620718796429
Konkle, BA, Stasyshyn, O, Chowdary, P, et al. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. Blood 2015; 126: 1078-85; https://doi.org/10.1182/blood-2015-03-630897
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: 317-25; https://doi.org/10.1182/blood-2013-10-529974
Giangrande P, Andreeva T, Chowdary P, et al. Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A. Thromb Haemost 2017; 117: 252-61; https://doi.org/10.1160/TH16-06-0444
Reding MT, Ng HJ, Poulsen LH, et al. Safety and efficacy of BAY 94-9027, a prolonged-half-life factor VIII. J Thromb Haemost 2017; 15: 411-9; https://doi.org/10.1111/jth.13597
Lalezari S, Reding MT, Pabinger I et al. BAY 94-9027 Prophylaxis Is Efficacious and Well Tolerated for Up to >5 Years With Extended Dosing Intervals: PROTECT VIII Extension Interim Results. Haemophilia 2019; 25: 1011-9; https://doi.org/10.1111/hae.13853
Adynovi® – Summary of product characteristics. Available at: https://www.ema.europa.eu/documents/product-information/adynovi-epar-product-information_it.pdf (last accessed January 2020)
Elocta® – Summary of product characteristics. Available at: https://ec.europa.eu/health/documents/community-register/2017/20170531138053/anx_138053_it.pdf (last accessed January 2020)
Esperoct® – Summary of product characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/esperoct-epar-product-information_en.pdf (last accessed January 2020)
Jivi® – Summary of product characteristics. Available at: https://www.ema.europa.eu/documents/product-information/jivi-epar-product-information_it.pdf (last accessed January 2020)
Wells J, Kessabi S, Vashi P, et al. Patient Perspectives on the Value of Longevity of Protection and Reduced Infusion Frequency for Prophylactic Treatment of Hemophilia A. National Hemophilia Foundation Bleeding Disorders Conference. Orlando, 2018
Wells JR, Gater A, Marshall C, et al. Exploring the Impact of Infusion Frequency in Hemophilia A: Exit Interviews with Patients Participating in BAY 94-9027 Extension Studies (PROTECT VIII). Patient 2019; 12: 611-9; https://doi.org/10.1007/s40271-019-00374-x
Kearney S, Raffini LJ, Pham TP, et al. Health-related quality-of-life and treatment satisfaction of individuals with hemophilia A treated with turoctocog alfa pegol (N8-GP): a new recombinant extended half-life FVIII. Patient Prefer Adherence 2019; 13: 497-513; https://doi.org/10.2147/PPA.S196103
Khair K, Pollard D, Harrison C, et al. How Patients view Extended half-life products: Impressions from real-world experience (The HOPE study). Haemophilia 2019; 25: 814-20; https://doi.org/10.1111/hae.13803
Agenzia Italiana Del Farmaco – AIFA. Determina 18 febbraio 2019. Classificazione, ai sensi dell’articolo 12, comma 5, della legge 8 novembre 2012, n. 189, dei medicinali per uso umano «Jivi» e «Pifeltro», approvati con procedura centralizzata. GU Serie Generale n.53 del 04-03-2019
Agenzia Italiana Del Farmaco – AIFA. Determina 3 gennaio 2020. Riclassificazione del medicinale per uso umano «Adynovi», ai sensi dell’articolo 8, comma 10, della legge 24 dicembre 1993, n. 537. GU Serie Generale n.14 del 18-01-2020
Agenzia Italiana Del Farmaco – AIFA. Determina 6 luglio 2016. Classificazione del medicinale per uso umano «Elocta», ai sensi dell’articolo 8, comma 10, della legge 24 dicembre 1993, n. 537. GU Serie Generale n.175 del 28-07-2016
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