“I’d go on a hike with my kids… that would make me feel so happy.” Recognising what people with haemophilia B identify as meaningful when considering personal goals and the potential for gene therapy

Kate Khair; Ranjit Nagra; Richard Gorman; Simon Fletcher; Kathryn Jenner; Joe Trim; Shuk-Li Collings

doi:10.2478/jhp-2025-0001

Abstract

Abstract Introduction

Historically people with haemophilia B (PwHB) have experienced adverse clinical outcomes including joint bleeds, pain and arthropathy. The current management of severe and moderate haemophilia B in the UK is largely through the use of factor replacement therapy often given as prophylaxis. Despite this, research reveals reduced quality of life (QoL) and psychological burden in PwHB of all severities, highlighting unmet need. Contemporary therapeutic developments including extended half-life factor IX products, novel non-factor agents, and gene therapy offer opportunities to address treatment-related issues and improve QoL. We investigated what PwHB identify as meaningful when considering their personal goals and the potential for gene therapy.

Methods

UK men (aged >16 years) with severe or moderate haemophilia B were invited to take part in a face-to-face workshop or one-to-one online audio recorded interview. The recordings were transcribed verbatim, the transcripts were reviewed and coded using a process of inductive thematic analysis. We then used an iterative process to explore, review, reflect, and refine emergent codes and final themes. Ethical approval was not required based on the UK Health Research Authority decision tool.

Results

Nine men, all with severe haemophilia B, aged 21 to 64 (median 34 years) participated. All were diagnosed as children; four had a previous family history and all described themselves as ‘well treated’ with self-managed home therapy and prophylaxis. None had received gene therapy. Parallels were observed in their goals. Thematic analysis classified them as achievable, unachievable and future goals.

Achievable goals: Achieved despite living with haemophilia B, included education and employment, strong personal relationships, having a family, travelling, having a good social life and being able to participate in sports.

Unachievable goals: Things that participants felt unable to achieve either now or in the future. These included changing attitudes of others, a recognition of lost opportunities including more physical, sporting and employment activities.

Future goals: Those which might be achieved as treatments evolve. This included being more physically active, improved QoL for affected individuals and their families, greater ability to travel, and optimism for future treatments and their potential impact for future generations.

The goals of PwHB often focused on personally meaningful everyday activities. Seemingly modest changes in individual circumstances could impact on QoL and wellbeing. QoL improvements were defined as equitable access to education and employment, increased confidence in undertaking physical activities, and greater ability to travel. Treatment innovations were identified as enhancing individualised patient preferences and reduced fear of bleeding along with its sequelae of pain and limited mobility.

Conclusion

With improved access to novel therapeutic options, including gene therapy, PwHB are potentially able to experience equity to people without haemophilia in day-to-day life and activities. This will enable them to reimagine individual goals, their sense of what is ‘achievable’ and live their lives in personally meaningful ways.

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References

1. Iorio A, Stonebraker JS, Chambost H, et al.; Data and Demographics Committee of the World Federation of Hemophilia. Establishing the prevalence and prevalence at birth of hemophilia in males: a meta-analytic approach using national registries. Ann Intern Med 2019; 171(8): 540–546. doi: https://doi.org/10.7326/M19-1208.
2. Di Michele DM, Gibb C, Lefkowitz JM, Ni Q, Gerber LM, Ganguly A. Severe and moderate haemophilia A and B in US females. Haemophilia 2014; 20(2): e136–43. doi: https://doi.org/10.1111/hae.12364.
3. Blanchette VS, Key NS, Ljung LR, et al.; Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost 2014; 12(11): 1935–9. doi: https://doi.org/10.1111/jth.12672.
4. Srivastava A, Santagostino E, Dougall A, et al. Guidelines for the management of hemophilia, 3rd edition. Haemophilia 2020; 26 (Suppl 6): 1–158. doi: https://doi.org/10.1111/j.1365-2516.2012.02909.x.
5. O’Hara J, Walsh S, Camp C, et al. The impact of severe haemophilia and the presence of target joints on health-related quality-of-life. Health Qual Life Outcomes 2018;16(1): 84. doi: https://doi.org/10.1186/s12955-018-0908-9.
6. Cavazza, M., Kodra, Y., Armeni, P. et al. Social/economic costs and quality of life in patients with haemophilia in Europe. Eur J Health Econ 2016; 17 (Suppl 1): 53–65. doi: https://doi.org/10.1007/s10198-016-0785-2.
7. Brod M, Bushnell DM, Neergaard JS, et al. Understanding treatment burden in hemophilia: development and validation of the Hemophilia Treatment Experience Measure (Hemo-TEM). J Patient Rep Outcomes 2023; 7: 17. doi: https://doi.org/10.1186/s41687/s4187-023-00550-6.
8. Buckner TW, Batt K, Quon D, et al. Assessments of pain, functional impairment, anxiety, and depression in US adults with hemophilia across patient-reported outcome instruments in the Pain, Functional Impairment, and Quality of Life (P-FiQ) study. Eur J Haematol 2018; 100: 5–13. doi: https://doi.org/10.1111/ejh.13027.
9. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357(6): 535–544. doi: https://doi.org/10.1056/NEJMoa067659.
10. Thornburg CD. Physicians’ perceptions of adherence to prophylactic clotting factor infusions. Haemophilia 2008; 14(1): 25–9. doi: https://doi.org/10.1111/j.1365-2516.2007.01591.x.
11. Mattis S, Barry V, Taylor N, et al. Disease-related distress among adults with haemophilia: A qualitative study. Haemophilia 2019; 25(6): 988–995. doi: https://doi.org/10.1111/hae.13850.
12. Wiley RE, Khoury CP, Snihur AWK, et al. From the voices of people with haemophilia A and their caregivers: Challenges with current treatment, their impact on quality of life and desired improvements in future therapies. Haemophilia 2019; 25(3): 433–440. doi: https://doi.org/10.1111/hae.13754.
13. Mahlangu J, Iorio A, Kenet G. Emicizumab state-of-the-art update. Haemophilia 2022; 28(Suppl 4): 103–110. doi: https://doi.org/10.1111/hae.14524.
14. Mancuso ME, Mahlangu JN, Pipe SW. The changing treatment landscape in haemophilia: from standard half-life clotting factor concentrates to gene editing. Lancet 2021; 397(10274): 630–640. doi: https://doi.org/10.1016/S0140-6736(20)32722-7.
15. Ucero-Lozano R, Pérez-Llanes R, Cuesta-Barriuso R et al. Changes in quality of life, adherence, and kinesiophobia in patients with hemophilia treated with extended half-life treatment: Final results of the LongHest Project. Pharmaceuticals (Basel) 2024 J; 17(7): 835. doi: https://doi.org/10.3390/ph17070835.
16. Konkle BA, Shapiro AD, Quon DV, et al. BIVV001 fusion protein as factor VIII replacement therapy for hemophilia A. N Engl J Med 2020; 383(11): 1018–1027. doi: https://doi.org/10.1182/blood.2019001292.
17. Pipe SW, Leebeek FWG, Recht M, et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med 2023; 388(8): 706–718. doi: https://doi.org/10.1056/NEJMoa2211644.
18. Shah J, Kim H, Sivamurthy K, et al. Comprehensive analysis and prediction of long-term durability of factor IX activity following tranacogene dezaparvovec gene therapy in the treatment of hemophilia B. Curr Med Res Opin 2023; 39(2): 227–237. doi: https://doi.org/10.1080/03007995.2022.2133492.
19. Mahlangu J, Kaczmarek R, DA von, et al. Two-year outcomes of valoctocogene roxaparvovec therapy for hemophilia A. N Engl J Med 2023; 388(8): 694–705. doi: https://doi.org/10.1056/NEJMoa2211075.
20. Pierce GF, Herzog RW. Two gene therapies for hemophilia available: now what? Mol Ther 2023; 31(4): 919–920. doi: https://doi.org/10.1016/j.ymthe.2023.03.001.
21. Valentino LA, Blanchette V, Negrier C, et al. Personalising haemophilia management with shared decision making. J Haem Pract 2021; 8(1): 69–79. doi: https://doi.org/10.17225/jhp00178.
22. Fletcher S, Jenner K, Pembroke L, et al. The experiences of people with haemophilia and their families of gene therapy in a clinical trial setting: regaining control, the Exigency study. Orphanet J Rare Dis 2022; 17(1): 155. doi: https://doi.org/10.1186/s13023-022-02256-2.
23. Fletcher S, Jenner K, Holland M, et al. Barriers to gene therapy, understanding the concerns people with haemophilia have: an exigency sub-study. Orphanet J Rare Dis 2024; 19(1): 59. doi: https://doi.org/10.1186/s13023-024-03068-2.
24. Owen H. Open Space Technology: A User’s Guide. 3rd edn. San Francisco: Berrett-Koehler Publishers, Inc.; 2008.
25. Wang M, Negrier C, Driessler F, et al. The hemophilia gene therapy patient journey: Questions and answers for shared decision-making. Patient Prefer Adherence 2022; 16: 1439–1447. doi: https://doi.org/10.2147/PPA.S355627.
26. UKRI Medical Research Council; NHS Health Research Authority. Is my study research? Available from https://www.hra-decisiontools.org.uk/research/ (accessed 01/07/2024).
27. Glaser BG and Strauss AL. The Discovery of Grounded Theory: Strategies for Qualitative Research. New York: Aldine Publishing Company; 1967.
28. Charmaz K. Constructing Grounded Theory. 2nd edition. Introducing Qualitative Methods series. London: SAGE Publications; 2014.
29. Gorman R, Woollard L. Is it time for patient involvement in Haemophilia? Haemophilia 2022; 28(3): e73–e74. doi: https://doi.org/10.1111/hae.14520.
30. Iorio A, Skinner MW, Clearfield E, et al. Core outcome set for gene therapy in haemophilia: results of the coreHEM multistakeholder project. Haemophilia 2018; 24(4): e167–72. doi: https://doi.org/10.1111/hae.13504.
31. Woolley KL, Stones SR, Stephens R, et al. Patient authorship of medical research publications: An evolution, revolution, and solution? Learned Publishing 2024; 37: e1607. doi: https://doi.org/10.1002/leap.1607.
32. Baas L, Meijer K, Bredenoord AL, van der Graaf R. What is a cure through gene therapy? An analysis and evaluation of the use of “cure”. Med Health Care Philos 2024. doi: https://doi.org/10.1007/s11019-024-10223-w. Epub ahead of print.
33. Krumb E, Hermans C. Living with a “hemophilia-free mind” – the new ambition of hemophilia care? Res Pract Thromb Haemost 2021; 5(5): e12567. doi: https://doi.org/10.1002/rth2.12567.
34. Hermans C, Pierce GF. Towards achieving a haemophilia-free mind. Haemophilia 2023; 29(4): 951–953. doi: https://doi.org/10.1111/hae.14807.
35. Hughes T, Brok-Kristensen, Gargeya Y, et al. “What more can we ask for?”: an ethnographic study of challenges and possibilities for people living with haemophilia. J Haem Pract 2020; 7(1): 25–36. doi: https://doi.org/10.17225/jhp00151.
36. Hughes T, Brok-Kristensen M, Gargeya Y, et al. “He’s a normal kid now”: an ethnographic study of challenges and possibilities in a new era of haemophilia care. J Haem Pract 2020; 7(1): 150–157. doi: https://doi.org/10.17225/jhp00167.
37. O’Hara J, Martin AP, Nugent D, et al. Evidence of a disability paradox in patient-reported outcomes in haemophilia. Haemophilia 2021; 27(2): 245–252. doi: https://doi.org/10.1111/hae.14278.
38. Albrecht GL, Devlieger PJ. The disability paradox: high quality of life against all odds. Soc Sci Med 1999; 48(8): 977–88. doi: https://doi.org/10.1016/s0277-9536(98)00411-0.
39. Shakespeare T. The social model of disability. In: Davis LJ (ed.). The Disability Studies Reader. 2nd ed. New York: Routledge; 2006. pp.197–204.
40. Goering S. Rethinking disability: the social model of disability and chronic disease. Curr Rev Musculoskeletal Med 2015; 8(2): 134–138. doi: https://doi.org/10.1007/s12178-015-9273-z.
41. Gorman R. Disabilities and geography. In: Warf B(ed.). The Encyclopedia of Human Geography. Springer; 2024. doi: https://doi.org/10.1007/978-3-031-25900-5
42. Berntorp E, LeBeau P, Ragni MV, et al. Quality of life in a large multinational haemophilia B cohort (The B-Natural study) – Unmet needs remain. Haemophilia 2022; 28(3): 453–461. doi: https://doi.org/10.1111/hae.14525.
43. Barlow JH, Stapley J, Ellard DR. Living with haemophilia and von Willebrand’s: A descriptive qualitative study. Patient Educ Couns 2007; 68(3): 235–42. doi: https://doi.org/0.1016/j.pec.2007.06.006.
44. Baas L, van der Graaf R, van Hoorn ES, et al. The ethics of gene therapy for hemophilia: a narrative review. J Thromb Haemost 2023; 21(3): 413–420. doi: https://doi.org/10.1016/j.jtha.2022.12.027.
45. NICE. Etranacogene dezaparvovec for treating moderately severe or severe haemophilia B. Technology appraisal guidance. TA989. Published 24 July 2024. https://www.nice.org.uk/guidance/TA989 (Accessed 19 October 2024).

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Authors

Kate Khair
Ranjit Nagra

Pfizer Ltd, Surrey, UK
Richard Gorman

Brighton and Sussex Medical School, University of Sussex, UK
Simon Fletcher

University of Oxford, Oxford UK
Kathryn Jenner

Haemnet Ltd, London, UK
Joe Trim

Pfizer Ltd, Surrey, UK
Shuk-Li Collings

Pfizer Ltd, Surrey, UK