How to discuss gene therapy for haemophilia? A patient and physician perspective

Abstract

Gene therapy has the potential to revolutionise treatment for patients with haemophilia and is close to entering clinical practice. While factor concentrates have improved outcomes, individuals still face a lifetime of injections, pain, progressive joint damage, the potential for inhibitor development and impaired quality of life. Recently published studies in adeno‐associated viral (AAV) vector‐mediated gene therapy have demonstrated improvement in endogenous factor levels over sustained periods, significant reduction in annualised bleed rates, lower exogenous factor usage and thus far a positive safety profile. In making the shared decision to proceed with gene therapy for haemophilia, physicians should make it clear that research is ongoing and that there are remaining evidence gaps, such as long‐term safety profiles and duration of treatment effect. The eligibility criteria for gene therapy trials mean that key patient groups may be excluded, eg children/adolescents, those with liver or kidney dysfunction and those with a prior history of factor inhibitors or pre‐existing neutralising AAV antibodies. Gene therapy offers a life‐changing opportunity for patients to reduce their bleeding risk while also reducing or abrogating the need for exogenous factor administration. Given the expanding evidence base, both physicians and patients will need sources of clear and reliable information to be able to discuss and judge the risks and benefits of treatment.

Patient perspectives regarding gene therapy in haemophilia: Interviews from the PAVING study

“…The content of the information sections and the rest of the interview guide were informed by a systematic literature review that resulted in the identification of 13 clinical trial publications and 19 patient preference studies/public meetings (Appendix S1 III). Moreover, information sections covered aspects highlighted in the work of Miesbach et al, 17 including but not limited to uncertainty in long-term safety and efficacy, eligibility criteria, variability in achieved outcomes, and current absence of major safety issues. The information sections were followed by open questions to investigate participants' attitudes towards gene therapy and reasons to refrain from or accept gene therapy.…”

Assessing the test–retest reliability and smallest detectable change of the Haemophilia Activities List

“…In developed countries, treatment of haemophilia has greatly improved over the last decades and life expectancy of PWH has almost normalized 3 . Especially now, with gene therapy as a promising next step in haemophilia care, 4 appropriate clinimetric instruments are essential to assess the effect of new (para)medical treatments and to monitor patients at individual level. Besides reporting bleeding episodes and joint assessment, measurement of the impact of haemophilia on activities and participation in relation with their society is important 1 …”

<p>The Patient Experience of Gene Therapy for Hemophilia: Qualitative Interviews with Trial Patients</p>

“…The current standard of care for people with hemophilia (PWH), the replacement of exogenous coagulation factor, has improved significantly in recent decades but remains suboptimal in terms of progressive joint damage, the potential for inhibitor development, poor adherence to therapy and reduced quality of life due to the need for lifelong intravenous injections. 1 Gene therapy is an attractive therapy strategy for PWH because it eliminates these limitations by providing the potential for stable long-term expression of endogenous coagulation factor activity with one single treatment.…”