The patient gene therapy journey: Findings from qualitative interviews with trial participants at one UK haemophilia centre

Elsa Aradom; Keith Gomez

doi:10.17225/jhp00174

Abstract

Abstract Introduction

Gene therapy for haemophilia is in late-stage clinical development and has the potential to become a therapeutic option in clinical practice.

Aims

To enhance the understanding of the perspectives of people with haemophilia around gene therapy, and to highlight their concerns about and motivations for having gene therapy.

Method

Structured, qualitative interviews were conducted and recorded with six people who had received an investigational gene therapy product. The recordings were transcribed and thematically analysed.

Results

Most of those interviewed were under the age of 40, and the mean time out from their gene therapy infusion was 10 months. Adverse events were the main concerns pre-infusion, and impact on quality of life was the main motivating factor for choosing to go ahead. Pre-infusion, the treating centre and the health care professionals working there were the main source of information regarding gene therapy; only two participants looked elsewhere for information to support their decision. None of the respondents expressed concerns about the infusion day itself, and all found the infusion to be simple or uneventful. Post-infusion, four found the frequency of follow-up appointments difficult, with time and travel the main issues.

Conclusion

Although participants' perspectives on gene therapy were generally positive, there remains a need for education and support. Nurses will play an important role in the delivery of gene therapy for haemophilia, but all staff within the haemophilia treatment centre should be armed with the knowledge and confidence to answer questions about gene therapy.

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References

1. Doshi BS, Arruda VR. Gene therapy for hemophilia: what does the future hold? Ther Adv Hematol 2018; 9(9): 273–93. doi: https://doi.org/10.1177/2040620718791933.
2. Ohmori T. Advances in gene therapy for hemophilia: basis, current status, and future perspectives. Int J Hematol 2020; 111(1): 31–41. doi: https://doi.org/10.1007/s12185-018-2513-4.
3. Ohmori T, Mizukami H, Ozawa K, Sakata Y, Nishimura S. New approaches to gene and cell therapy for hemophilia. J Thromb Haemost 2015; 13(suppl 1): S133–42. doi: https://doi.org/10.1111/jth.12926.
4. Kumar SRP, Markusic DM, Biswas M, High KA, Herzog RW. Clinical development of gene therapy: results and lessons from recent successes. Mol Ther Methods Clin Dev 2016; 3: 16034. doi: https://doi.org/10.1038/mtm.2016.34.
5. Pasi KJ, Rangarajan S, Mitchell N, et al. Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A. N Engl J Med 2020; 382: 29–40. doi: https://doi.org/10.1056/NEJMoa1908490.
6. Pipe S, Becka M, Detering E, Vanevski K, Lissitchkov T. First-in-human gene therapy study of AAVhu37 capsid vector technology in severe hemophilia A. Blood 2019; 134 (Supplement 1): 4630. doi: https://doi.org/10.1182/blood-2019-125764.
7. Konkle BA, Stine K, Visweshwar N, et al. Initial results of the Alta Study, a phase 1/2, open label, adaptive, dose-ranging study to assess the safety and tolerability of SB-525 gene therapy in adult subjects with severe hemophilia A. Blood 2019; 134 (Supplement 1): 2060. doi: https://doi.org/10.1182/blood-2019-122143.
8. High KA, George LA, Eyster ME, et al. A phase 1/2 trial of investigational Spk-8011 in hemophilia A demonstrates durable expression and prevention of bleeds. Blood 2018; 132 (Supplement 1): 487. doi: https://doi.org/10.1182/blood-2018-99-115495.
9. Nathwani AC, Reiss U, Tuddenham E, et al. Adeno-associated mediated gene transfer for hemophilia B: 8 year follow up and impact of removing “empty viral particles” on safety and efficacy of gene transfer. Blood 2018; 132 (Supplement 1): 491. doi: https://doi.org/10.1182/blood-2018-99-118334.
10. Chowdary P, Shapiro S, Boyce S, et al. FLT180a: next generation AAV vector for haemophilia B – long term, follow-up and in-depth analysis of transgenic FIX using one-stage, chromogenic and global assays. ISTH Academy 2019; 263496; PB0309.
11. Nathwani AC, Reiss UM, Tuddenham EGD, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 2014; 371(21): 1994–2004. doi: https://doi.org/10.1056/NEJMoa1407309.
12. Leebeek FWG, Meijer K, Coppens M, et al. Stable expression of FIX and maintained reductions in bleeding and factor IX consumption following AMT-060 gene therapy with up to 3.5 years of follow up in adults with severe or moderate-severe hemophilia B. ISTH Academy 2019; 274036; OC 01.4.
13. Von Drygalski A, Giermasz A, Castaman G, et al. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv 2019; 3(21): 3241–47. doi: https://doi.org/10.1182/bloodadvances.2019000811.
14. George LA, Sullivan SK, Rasko JEJ, et al. Efficacy and safety in 15 hemophilia B patients treated with the AAV gene therapy vector fidanacogene elaparvovec and followed for at least 1 year. Blood 2019; 134 (Supplement 1): 3347. doi: https://doi.org/10.1182/blood-2019-124091.
15. Stoffman J, Andersson NG, Branchford B, et al. Common themes and challenges in hemophilia care: a multinational perspective. Hematology 2019; 24: 39–48. doi: https://doi.org/10.1080/10245332.2018.1505225.
16. Pollard D, Harrison C, Dodgson S, Holland M, Khair K. The UK haemophilia specialist nurse: Competencies fit for practice in the 21st century. Haemophilia 2020; 26(4): 622–30. doi: https://doi.org/10.1111/hae.14002.
17. Miesbach W, Klamroth R. The patient experience of gene therapy for hemophilia: qualitative interviews with trial patients. Patient Pref Adherence 2020; 14: 767–70. doi: https://doi.org/10.2147/PPA.S239810.
18. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol 2008; 3: 77–101. doi: https://doi.org/10.1191/1478088706qp063oa.
19. Sundler AJ, Lindberg E, Nilsson C, Palmér L. Qualitative thematic analysis based on descriptive phenomenology. Nurs Open 2019; 6(3): 733–9. doi: https://doi.org/10.1002/nop2.275.
20. UKRI Medical Research Council. Is my study research? Available from http://www.hra-decisiontools.org.uk/research/ (accessed 15 March 2021).
21. Van Balen EC, Wesselo ML, Baker BL, et al. Patient perspectives on novel treatments in haemophilia: a qualitative study. Patient 2020; 13(2): 201–10. doi: https://doi.org/10.1007/s40271-019-00395-6.
22. Costea I, Isasi R, Knoppers BM, Lillicrap D. Haemophilia gene therapy: the patients' perspective. Haemophilia 2009; 15(5): 1159–61. doi: https://doi.org/10.1111/j.1365-2516.2009.02065.x.
23. Woollard L, Gorman R, Rosenfelt DJ. Addressing patient education priorities in the era of gene therapy for haemophilia: Towards evidence–informed shared decision–making. Haemophilia 2020 Nov 27. doi: https://doi.org/10.1111/hae.14214. Online ahead of print.
24. Peyvandi F, Lillicrap D, Mahlangu J, et al. Hemophilia gene therapy knowledge and perceptions: Results of an international survey. Res Pract Thromb Haemost 2020; 4(4): 644–51. doi: https://doi.org/10.1002/rth2.12326.
25. Arcé C, Branchford B, Hart DP, et al. Optimizing language for effective communication of gene therapy concepts: A qualitative study. Presented at NHF Bleeding Disorders Conference 2019; PSO71. Available from https://www.hemophilia.org/research/research-projects/optimizing-language-for-effective-communication-of-gene-therapy-concepts-a-qualitative-study (accessed 15 March 2021).
26. Morris J. Patient advocacy helps patients weigh up gene therapy trial risk/benefits. J Haem Pract 2015; 2(1): 6–8. doi: https://doi.org/10.17225/jhp.00040.
27. Forrester C, Bielby H, Johns S, Efford J, Holland M, Khair K, United Kingdom Haemophilia Nurse's Association. Potential for development of haemophilia link nurse role within UK hospitals. Haemophilia 2013; 19(4): 578–82. doi: https://doi.org/10.1111/hae.12144.
28. Khair K. Supporting adherence and improving quality of life in haemophilia care. Br J Nurs 2013; 22(12): 692. doi: https://doi.org/10.12968/bjon.2013.22.12.692.
29. Knobe K, Berntorp E. Haemophilia and joint disease: pathophysiology, evaluation, and management. J Comorb 2011; 1: 51–9. doi: https://doi.org/10.15256/joc.2011.1.2.
30. Harrington C, Bedford M, Andritschke K, et al; EAHAD Nurses Committee. A European curriculum for nurses working in haemophilia. Haemophilia 2016; 22: 103–9. doi: https://doi.org/10.1111/hae.12785.
31. Khair K. Minimizing joint damage: the role of nurses in promoting adherence to hemophilia treatment. Orthop Nurs 2010; 29(3): 193–200. doi: https://doi.org/10.1097/NOR.0b013e3181db53e8.
32. Pierce GF, Coffin D, members of the WFH Gene Therapy Round Table Program Committee and Organizing Committee. The 1st WFH gene therapy round table: understanding the landscape and challenges of gene therapy for haemophilia around the world. Haemophilia 2019; 25(2): 189–194. doi: https://doi.org/10.1111/hae.13673.
33. Hurst S, Warren C, Pasi KJ. Gene therapy in hemophilia: an assessment of hematologists’ knowledge gaps and attitudes. Blood; 2018; 132 (Supplement 1): 3485. doi: https://doi.org/10.1182/blood-2018-99-119116.
34. High KA, Roncarolo MG. Gene therapy. N Engl J Med 2019; 381: 455–64. doi: https://doi.org/10.1056/NEJMra1706910.
35. Mulders G, De Wee EM, Vahedi Nikbakht-Van De Sande MCVM, Kruip MJHA, Elfrink EJ, Leebeek FWG. E-learning improves knowledge and practical skills in haemophilia patients on home treatment: a randomized controlled trial. Haemophilia 2012; 18(5): 693–8. doi: https://doi.org/10.1111/j.1365-2516.2012.02786.x.
36. Miesbach W, O’Mahony B, Key NS, Makris M. How to discuss gene therapy for haemophilia? A patient and physician perspective. Haemophilia 2019; 25(4): 545–57. doi: https://doi.org/10.1111/hae.13769.

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Authors

Elsa Aradom

elsa.aradom@nhs.net

Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, UK .
Keith Gomez

Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, UK .