Awareness of individual goals, preferences, and priorities of persons with severe congenital haemophilia A for a tailored shared decision-making approach to liver-directed gene therapy. A practical guideline

Di Minno, Giovanni; Spadarella, Gaia; Maldonato, Nelson Mauro; De Lucia, Natascia; Castaman, Giancarlo; De Cristofaro, Raimondo; Santoro, Cristina; Peyvandi, Flora; Borrelli, Anna; Lupi, Angelo; Follino, Marco; Guerrino, Gerardo; Morisco, Filomena; Di Minno, Matteo

doi:10.1016/j.blre.2023.101118

Cited by 3 publications

(1 citation statement)

References 143 publications

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“…8 Simultaneously, treatment selection has become increasingly challenging, being influenced by factors such as safety and efficacy, mechanism of action, administration route, availability, insurance coverage/reimbursement, healthcare practitioner (HCP) preferences and influence, and patient preferences and priorities. [9][10][11][12] Given the complex therapeutic landscape for haemophilia, it is critical that persons with haemophilia (PWH) actively participate in discussions regarding their medical care. 9 Shared decision-making (SDM) is a patient-centred approach involving reciprocal sharing of information between PWH (or their caregiver) and the HCP.…”

Section: Introductionmentioning

confidence: 99%

Shared decision‐making related to treatment of haemophilia: A scoping review of influential factors and available support tools

Sun,

Klaassen,

Anger

et al. 2024

Haemophilia

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IntroductionTreatment selection in haemophilia is increasingly challenging given evolving therapeutic options and the need for individualization. Shared decision‐making (SDM) approaches have recently gained interest, though a synthesis of available studies is lacking.AimA scoping review was conducted to summarize literature reporting on factors impacting treatment SDM in haemophilia and tools or models available to support such decisions.MethodsPubMed, Embase, the Cochrane Library, Web of Science and grey literature were searched for studies published through August 2023. Original studies reporting on facilitators and barriers to haemophilia SDM and SDM tools were included and analyzed for themes, characteristics and gaps.ResultsA total of 625 records were identified and 14 unique studies were selected (factors influencing treatment SDM, n = 7; SDM tools, n = 7). The studies typically included input from persons with haemophilia, caregivers and healthcare practitioners (HCPs). Thematic organization of factors influencing SDM revealed three main categories: knowledge, patient characteristics and HCP‐patient interactions. Availability of information was a commonly reported facilitator of SDM, while poor HCP‐patient engagement was a commonly reported barrier. Tools varied in focus, with some facilitating general treatment SDM while others supported selection of certain therapy types. The studies underscored additional factors critical for SDM, such as alignment of HCP‐patient perceptions, shared language and tailoring of tools to specific subpopulations.ConclusionFew studies report on treatment SDM factors and tools in haemophilia; available tools vary considerably. It remains unclear whether published tools have been successfully implemented into clinical practice. Additional research is warranted.

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Section: Introductionmentioning

confidence: 99%

Shared decision‐making related to treatment of haemophilia: A scoping review of influential factors and available support tools

Sun,

Klaassen,

Anger

et al. 2024

Haemophilia

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Drug‐induced liver injury related to gene therapy: A new challenge to be managed

Larrey,

Delire,

Meunier

et al. 2024

Liver International

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Gene therapy is being successfully developed for the treatment of several genetic disorders. Various methods of gene transfer have been developed to enable the production of the deficient enzyme or protein. One of the most important is adeno‐associated virus vectors, which have been shown to be viable for use in in vivo gene therapy. Several gene therapies have already been approved. They are also promising for acquired diseases. Important examples include gene therapy for haemophilia A and B, X‐linked myotubular myopathy, spinal muscular atrophy and several liver diseases such as Criggler‐Najjar disease, alpha‐1 antitrypsin deficiency and Fabry disease. However, the introduction of a foreign compound into hepatocytes leads to hepatic reactions with heterogeneous phenotypic expression and a wide spectrum of severity, ranging from mild transaminase elevation to acute liver failure. Several mechanisms appear to be involved in liver injury, including an immune response, but also direct toxicity depending on the method of gene transfer. As a result, the incidence, expression and severity of liver injury vary from indication to indication and from patient to patient. Patients treated for haemophilia A are more prone to transaminase elevation than those treated for haemophilia B. Corticosteroids are successfully used to correct liver reactions but also to prevent degradation of the transferred gene and loss of therapeutic activity. The aim of this review is to describe the risk of liver injury according to the indication for gene therapy and the short‐ and long‐term management currently proposed to prevent or correct liver reactions in clinical practice.

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Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice

La Mura,

Cardinale,

De Cristofaro

et al. 2024

Blood Advances

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Adeno-associated virus–based gene therapy (valoctocogene roxaparvovec) is an attractive treatment for hemophilia A. Careful clinical management is required to minimize the risk of hepatotoxicity, including assessment of baseline liver condition to determine treatment eligibility and monitoring liver function after gene therapy. This article describes recommendations (developed by a group of hemophilia experts) on hepatic function monitoring before and after gene therapy. To prevent harmful liver-related effects, gene therapy is contraindicated in patients with uncontrolled liver infections, autoimmune hepatitis, liver stiffness ≥8 kPa, or cirrhosis. Before using gene therapy in patients with liver steatosis or other liver disorders, the risk of liver damage should be considered using a highly individualized approach. Treatment is not recommended in patients with abnormal liver enzymes, including alanine aminotransferase (ALT) at any level above the upper limit of normal (ULN). Therefore, pretreatment assessment of liver health should include laboratory tests, abdominal ultrasound, and liver stiffness measurements by transient elastography (TE). In the first year after therapy, ALT levels should be monitored 1 to 2 times per week to detect elevations ≥1.5× ULN, which may require immunosuppressant therapy. Patients with ALT elevation should receive prednisone 60 mg/d for 2 weeks, followed by stepwise tapering when ALT returns to baseline. ALT monitoring should continue long term (every 3-6 months), along with abdominal ultrasound (every 6 months) and TE (yearly) evaluations. When patients with good liver health are selected for treatment and closely monitored thereafter, ALT elevations can be promptly treated and are expected to resolve without long-term hepatic sequelae.

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Awareness of individual goals, preferences, and priorities of persons with severe congenital haemophilia A for a tailored shared decision-making approach to liver-directed gene therapy. A practical guideline

Cited by 3 publications

References 143 publications

Shared decision‐making related to treatment of haemophilia: A scoping review of influential factors and available support tools

Shared decision‐making related to treatment of haemophilia: A scoping review of influential factors and available support tools

Drug‐induced liver injury related to gene therapy: A new challenge to be managed

Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice

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