Abstract
BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in the survival motor neuron gene, SMN1. Loss of SMN1 function results in deficiency of the SMN protein leading to motor neuron death, muscle wasting, and progressive loss of motor function. Two disease modifying therapies have been approved for teens and adults in the United States, with many more potential treatments in the drug development pipeline. As treatment options for teens and adults with SMA increase, a validated core set of outcome measures is needed to assess motor function, perceived fatigue, and perceived fatigability. The aim of this study was to determine which type of outcome measures best captures changes in disease status in teens and adults with SMA. RESULTS: In the first phase of this two-part study, a working group of key opinion leaders in SMA research and clinical care was surveyed using a modified Delphi method. The working group concluded that a patient-reported outcome measure based on activities of daily living (ADLs) would be the best way to capture changes in function, perceived fatigue, and perceived fatigability that are meaningful to clinicians, as well as teens and adults living with SMA. In the second phase of the study, two discussion groups of adults (non-ambulatory or ambulatory) were interviewed for their perspectives about which ADLs are most important to them, and about how perceived fatigue affects their abilities to perform these ADLs. Both discussion groups prioritized ADLs that related to independence and dignity. Non-ambulatory and ambulatory participants also reported that perceived fatigue and fatigability are a major factor in their ability to perform ADLs. CONCLUSION: SMA key opinion leaders and adults with SMA agreed that ADLs would be sensitive and impactful outcomes in the assessment of function, perceived fatigue, and perceived fatigability. The findings of this study form a foundation for reaching consensus around a core set of outcome measures for assessing disease status, perceived fatigue, and perceived fatigability in teens and adults with SMA in the U.S.