Defining meaningful treatment outcomes in adults with spinal muscular atrophy: an expert consensus approach

Introduction Adults living with spinal muscular atrophy (SMA) are a heterogeneous population, with wide-ranging functional abilities and symptom severity. Currently, disease-modifying treatment effects are inconsistently measured in adult persons with SMA, which can impact access to treatment and quality of care. This study aims to identify, through expert consensus from healthcare professionals and patient advocacy group representatives, opinion on clinically meaningful treatment outcomes for adults with SMA. Methods A modified-Delphi study (two online survey rounds and a final consensus meeting) was conducted. The surveys captured key concepts of importance and aimed to understand constructs nearing consensus for discussion in the final meeting. Consensus was defined as ≥80% of panelists showing disagreement or agreement. Results Data were collected from neurologists, allied health professionals, and patient advocacy group representatives from across the United States and Europe (France, Germany, Italy, Spain, and the United Kingdom). Panelists reached consensus that the greatest needs for adults with SMA include greater independence and ability to perform activities of daily living, access to treatment that could preserve function and achieve disease stabilization, preservation of respiratory abilities for improved survival, and ensuring access to treatments and equipment. Panelists agreed that a meaningful treatment outcome should be defined by improvements in physical functioning, stabilization and maintenance in physical functioning, or any improvement in health-related quality of life. Consensus was reached that the definition of a meaningful treatment outcome depends on functional class, and that this definition evolves with disease progression. Panelists also agreed that disease stabilization is an important outcome across all key dimensions. Discussion Expert consensus was obtained on what constructs should be considered when determining meaningful treatment outcomes in adults with SMA, and how such outcomes should be interpreted. By establishing consensus on outcomes such as disease stabilization, this work supports a patient-centered approach to care. Our study highlights that relying on motor scales alone may not capture meaningful treatment benefit, particularly when stabilization in other outcomes are most relevant to adults with SMA. Our findings support shared decision-making, setting realistic and personalized therapeutic goals in clinical practice, and advocate for access to appropriate therapies and equipment.