PRO119 Symptoms and Impacts of Nonsense Mutation Duchenne Muscular Dystrophy: A Qualitative Study and the Development of a Patient-Centred Conceptual MODEL

Abstract

Duchenne muscular dystrophy (DMD) is a rare genetic neuromuscular disorder which primarily affects boys. It causes progressive muscle degeneration and weakness which leads to loss of motor function and premature death. It is typically diagnosed before the age of five as a result of a delay in reaching motor milestones. Around 10-15% of cases are caused by a nonsense mutation (nmDMD). This study aimed to understand the symptoms of nmDMD and its impact on health-related quality of life (HRQoL). Qualitative interviews were conducted with caregivers of individuals with nmDMD treated with ataluren in the UK. An interview guide, developed with input from clinical experts and patient advocacy groups, explored key concepts (symptoms and impacts) associated with nmDMD prior to complete loss of ambulation. Interviews were conducted by telephone, recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. A conceptual model was developed to illustrate the relationship between symptoms and impacts. Ten interviews were conducted with the parents of individuals aged 4-19 years. Key symptoms identified were muscle weakness and muscle breakdown, which were associated with limitations in physical functioning (lower limb function, core strength, upper limb function) and pain. Other core concepts included fatigue and cognitive-behavioural symptoms (e.g. learning difficulties and behavioural issues). These symptoms impacted people’s daily activities (e.g. limitations with self-care), social activities (e.g. difficulty keeping up with others) and emotional wellbeing (e.g. frustration). These concepts and relationships were illustrated in a conceptual model. Positive and negative moderating factors (e.g. support and treatment) were discussed. Caregivers reported a range of interrelated symptoms and functional issues which impacted the broader HRQoL of individuals with nmDMD. Treatments which address the high unmet need in this population by improving symptoms, functioning, or delaying progression have the potential to improve HRQoL in these individuals.