Health Outcomes in Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by a homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene on chromosome 5q13, leading to progressive muscle weakness and atrophy. Although SMA is clinically very heterogeneous, it usually has a huge impact on the health-related quality of life of patients, their families and society. Studies revealed that the landscape of SMA has changed over the past few years. Different therapeutic approaches such as antisense oligonucleotides, small molecules or gene therapy show increased life expectancy and motor and respiratory improvements. However, it has become increasingly apparent that outcome measures used in clinical trials are inadequate to assess the full range of disease severity in real life, both from the patients’ and caregivers’ perspective and from the clinicians’ perspective. Respiratory and bulbar functions as well as mobility were identified as the priority areas in which treatments should have an effect in a survey involving 822 patients with type II and III SMA from Europe. In a qualitative study conducted in the United States, 123 patients, caregivers and clinicians considered that outcome measures should assess other important features of SMA, including the ability to perform daily activities, respiratory function, swallowing, fatigue and endurance. Mobility, self-toileting and feeding, spending time alone, independence and being engaged in social activities/building relationships were the aspects of quality of life and activities of daily living that matter most as possible treatment benefits in a survey of 298 adults with type I–IV SMA and caregivers in the USA. A recent qualitative study carried out in Spain by the Spinal Muscular Atrophy Foundation (FundAME) assessed five focus groups with different types of SMA patients and parents to identify which were the main areas of daily life that were impacted by the disease.

Course of the disease and response to treatments

Mobility, fatigue and endurance, pain, scoliosis, contractures and hip dislocation, feeding, breathing and voice, sleep and rest, vulnerability, infections and hospitalizations, and time spent in caring activities were the most impactful areas in the study. It was announced that the aim of this study was to assess the psychometric properties of a set of existing questionnaires and new items to gather information on the impact of SMA on physical, psychological, social and functional domains from the patients’ and caregivers’ perspective. This prospective, non-interventional study was conducted at 12 hospital-based neuromuscular clinics specialized in the management of patients with SMA in Spain. A multidisciplinary research team of pediatric and adult neurologists and rehabilitation physicians and a patient representative participated in the study design and it was reported that the panel selected key disease dimensions of mobility-independence, fatigue and endurance, pain, fatigability, breathing and voice, sleep and rest and vulnerability, and the measurements thereof. Patients aged 2 years and older with a confirmed diagnosis of 5q-autosomal recessive SMA were included in the study. Researchers underlined that the development of robust outcome measures in collaboration with the patient community is essential to determine what is meaningful to patients and their caregivers. Scientists expressed that this study will provide them with a comprehensive set of tools to better capture the course of the disease and the response to treatments. Researchers also stated that this study protocol is also a good example of a patient advocacy group working successfully with a multidisciplinary team of healthcare professionals caring for patients with SMA, and may serve as a model for similar initiatives in other countries.