Patient Perspective on Disease Burden and Gene Therapy for Hemophilia A and B: The “Haemvolution for Patients” Italian Survey

Maria Francesca Mansueto; Sarah Bigi; Marco Follino; Angelo Lupi; Antonio Coppola

doi:10.1055/s-0044-1787664

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2025; 51(01): 049-057
DOI: 10.1055/s-0044-1787664

Review Article

Patient Perspective on Disease Burden and Gene Therapy for Hemophilia A and B: The “Haemvolution for Patients” Italian Survey

Maria Francesca Mansueto

¹Centro Emofila e Divisione di Ematologia, Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone, Palermo, Italy

,

Sarah Bigi

²Dipartimento di Scienze Linguistiche e Letterature Straniere, Università Cattolica del Sacro Cuore, Milan, Italy

,

Marco Follino

³Fondazione Paracelso Onlus, Milan, Italy

,

Angelo Lupi

⁴Federation of Haemophilia Associations (FedEmo), Rome, Italy

,

Antonio Coppola

⁵Regional Reference Centre for Inherited Bleeding Disorders, Department of General and Specialist Medicine, University Hospital of Parma, Parma, Italy

› Author Affiliations

Abstract

Hemophilia is a rare X-linked congenital bleeding disorder due to a deficiency of factor VIII (hemophilia A [HA]) or factor IX (hemophilia B [HB]). Replacement and nonreplacement treatments are available but have limitations. Gene therapy (GT) provides an effective, long-term, single-dose treatment option, now approaching clinical practice. This study aimed to understand patient perspectives on GT for HA and HB in Italy using a qualitative questionnaire distributed through Italian patient associations, addressing patient views on daily life, treatments, unmet needs, quality of life (QoL), and GT for hemophilia. In total, 141 participants had HA, and 14 had HB (severe 78.6%). Daily life was most affected by pain and/or joint function limitations (57.5% of participants), high infusion frequency (42.5%), management of breakthrough bleeding episodes (40.3%), and anxiety/fear of severe or sudden bleeding (38.8%). Despite current treatments, about half of the participants experienced three or more annual bleeding episodes. Most participants knew of GT (87.2%) and expected improvements in QoL (60.5%), reduced frequency of current treatments (53.5%), and a permanent cure (49.1%); 46.4% were unaware of its once-off dosage and 46.4% were not concerned about the costs they anticipated to be associated with GT. Although several fears were reported, 25.0% of participants were willing to undergo GT with the support of a multidisciplinary team. This survey provided valuable insight into patient perspectives on hemophilia and GT in Italy. Overall, relevant proportions of patients still experience limitations affecting their daily life. Most were positive about GT and anticipated improvements in their clinical outcomes and QoL.

Keywords

disease burden - gene therapy - hemophilia - patient awareness - patient perspective

Full Text

References

References
1 Srivastava A, Santagostino E, Dougall A. et al. WFH Guidelines for the management of hemophilia, 3rd edition. Haemophilia 2020; 26 (Suppl. 06) 1-158
2 Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet 2016; 388 (10040): 187-197
3 Rodríguez-Merchán EC, De Pablo-Moreno JA, Liras A. Gene therapy in hemophilia: recent advances. Int J Mol Sci 2021; 22 (14) 7647
4 Abbonizio F, Hassan HJ, Riccioni R, Santagostino E, Arcieri R, Giampaolo A. Italian Association of Haemophilia Centres (see Appendix). New data from the Italian National Register of Congenital Coagulopathies, 2016 Annual Survey. Blood Transfus 2020; 18 (01) 58-66
5 Rodriguez-Merchan EC. Articular bleeding in hemophilia. Cardiovasc Hematol Disord Drug Targets 2016; 16 (01) 21-24
6 Kempton CL, Recht M, Neff A. et al. Impact of pain and functional impairment in US adults with haemophilia: Patient-reported outcomes and musculoskeletal evaluation in the pain, functional impairment and quality of life (P-FiQ) study. Haemophilia 2018; 24 (02) 261-270
7 Holstein K, Klamroth R, Richards M, Carvalho M, Pérez-Garrido R, Gringeri A. European Haemophilia Therapy Standardization Board. Pain management in patients with haemophilia: a European survey. Haemophilia 2012; 18 (05) 743-752
8 Tagliaferri A, Franchini M, Rivolta GF, Farace S, Quintavalle G, Coppola A. ad hoc Study Group. Pain assessment and management in haemophilia: A survey among Italian patients and specialist physicians. Haemophilia 2018; 24 (05) 766-773
9 Berntorp E, Fischer K, Hart DP. et al. Haemophilia. Nat Rev Dis Primers 2021; 7 (01) 45
10 Di Minno G, Castaman G, De Cristofaro R. et al. Progress, and prospects in the therapeutic armamentarium of persons with congenital hemophilia. Defining the place for liver-directed gene therapy. Blood Rev 2023; 58: 101011
11 Batorova A, Boban A, Brinza M. et al. Expert opinion on current and future prophylaxis therapies aimed at improving protection for people with hemophilia A. J Med Life 2022; 15 (04) 570-578
12 Castaman G, Linari S. Prophylactic versus on-demand treatments for hemophilia: advantages and drawbacks. Expert Rev Hematol 2018; 11 (07) 567-576
13 Castaman G, Di Minno G, De Cristofaro R, Peyvandi F. The arrival of gene therapy for patients with hemophilia A. Int J Mol Sci 2022; 23 (18) 10228
14 Perrin GQ, Herzog RW, Markusic DM. Update on clinical gene therapy for hemophilia. Blood 2019; 133 (05) 407-414
15 European Medicines Agency. Roctavian (valoctocogene roxaparvovec): Summary of Product Characteristics. 2022 Accessed June 12, 2023 at: https://www.ema.europa.eu/en/documents/product-information/roctavian-epar-product-information_en.pdf
16 Ozelo MC, Mahlangu J, Pasi KJ. et al; GENEr8-1 Trial Group. Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med 2022; 386 (11) 1013-1025
17 Mahlangu J, Kaczmarek R, von Drygalski A. et al; GENEr8-1 Trial Group. Two-year outcomes of valoctocogene roxaparvovec therapy for hemophilia A. N Engl J Med 2023; 388 (08) 694-705
18 Pasi KJ, Laffan M, Rangarajan S. et al. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia 2021; 27 (06) 947-956
19 Pipe SW, Leebeek FWG, Recht M. et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med 2023; 388 (08) 706-718
20 Castaman G, Carulli C, De Cristofaro R. et al. Laying the foundations for gene therapy in Italy for patients with haemophilia A: A Delphi consensus study. Haemophilia 2023; 29 (02) 435-444
21 Abbonizio F, Biffoni M, Arcieri R, Giampaolo A. Italian Association of Haemophilia Centers (AICE). National Registry of Congenital Coagulopathies. Report 2020. Rome: National Institute of Health, ISTISAN Reports 22/38 (in Italian); 2022. . Accessed 16 April 2024 at: https://www.iss.it/-/rappporto-istisan-22/38-registro-nazionale-coagulopatie-congenite.-rapporto-2020.-francesca-abbonizio-mauro-biffoni-romano-arcieri-associazione-italiana-centri-emofilia-aice-adele-giampaolo
22 Kalnins W, Schelle G, Jost K, Eberl W, Tiede A. Pain therapy in haemophilia in Germany. Patient survey (BESTH study). Hamostaseologie 2015; 35 (02) 167-173
23 Kodra Y, Cavazza M, Schieppati A. et al. The social burden and quality of life of patients with haemophilia in Italy. Blood Transfus 2014; 12 (Suppl. 03) s567-s575
24 Banchev A, Batorova A, Faganel Kotnik B. et al; Patient Advocacy Group. A cross-national survey of people living with hemophilia: impact on daily living and patient education in Central Europe. Patient Prefer Adherence 2021; 15: 871-883
25 Forsyth AL, Witkop M, Lambing A. et al. Associations of quality of life, pain, and self-reported arthritis with age, employment, bleed rate, and utilization of hemophilia treatment center and health care provider services: results in adults with hemophilia in the HERO study. Patient Prefer Adherence 2015; 9: 1549-1560
26 Shapiro S, Makris M. Haemophilia and ageing. Br J Haematol 2019; 184 (05) 712-720
27 Schultz DM, Beukenhorst AL, Yimer BB. et al. Weather patterns associated with pain in chronic-pain sufferers. BAMS 2020; 101: E555-E566
28 Zetterberg E, Ljungkvist M, Salim M. Impact of exercise on hemophilia. Semin Thromb Hemost 2018; 44 (08) 787-795
29 Biasoli C, Baldacci E, Coppola A. et al; MEMO Study Group (Appendix I). Promoting physical activity in people with haemophilia: the MEMO (Movement for persons with haEMOphilia) expert consensus project. Blood Transfus 2022; 20 (01) 66-77
30 Zanon E, Tagliaferri A, Pasca S. et al. Physical activity improved by adherence to prophylaxis in an Italian population of children, adolescents and adults with severe haemophilia A: the SHAPE Study. Blood Transfus 2020; 18 (02) 152-158
31 O'Hara J, Noone D, Watt M. Relationship between bleeding episodes, health-related quality of life and direct costs in adults with severe haemophilia A: Secondary analyses from the CHESS study. Haemophilia 2022; 28 (05) e117-e120
32 Fischer K, Steen Carlsson K, Petrini P. et al. Intermediate-dose versus high-dose prophylaxis for severe hemophilia: comparing outcome and costs since the 1970s. Blood 2013; 122 (07) 1129-1136
33 Rocino A, Coppola A, Franchini M. et al; Italian Association of Haemophilia Centres (AICE) Working Party. Principles of treatment and update of recommendations for the management of haemophilia and congenital bleeding disorders in Italy. Blood Transfus 2014; 12 (04) 575-598
34 Stromer W, Pabinger I, Ay C. et al. Pain management in hemophilia: expert recommendations. Wien Klin Wochenschr 2021; 133 (19-20): 1042-1056
35 Croteau SE. Evolving complexity in hemophilia management. Pediatr Clin North Am 2018; 65 (03) 407-425
36 Hu YF, Fang YH, Lai YR, Feng XQ, Xu SQ. Application of gene therapy in hemophilia. Curr Med Sci 2022; 42 (05) 925-931
37 Swire-Thompson B, Lazer D. Public health and online misinformation: challenges and recommendations. Annu Rev Public Health 2020; 41: 433-451
38 Cook K, Forbes SP, Adamski K, Ma JJ, Chawla A, Garrison Jr LP. Assessing the potential cost-effectiveness of a gene therapy for the treatment of hemophilia A. J Med Econ 2020; 23 (05) 501-512
39 Bolous NS, Chen Y, Wang H. et al. The cost-effectiveness of gene therapy for severe hemophilia B: a microsimulation study from the United States perspective. Blood 2021; 138 (18) 1677-1690
40 Salzman R, Cook F, Hunt T. et al. Addressing the value of gene therapy and enhancing patient access to transformative treatments. Mol Ther 2018; 26 (12) 2717-2726

Supplementary Material

Supplementary Material