Background and Objective: Patients with spinal muscular atrophy (SMA) treated with a disease-modifying therapy (DMT) are often classified as responders or non-responders based on the attainment of a specific improvement threshold on validated functional scales. This categorization may significantly impact treatment reimbursement in some countries. The aim of this research is to evaluate the perception of treatments and their benefit by patients considered as responders or non-responders. Methods: In this non-commercial multicenter study, 99 post-symptomatically treated SMA type I-III patients with a median age of 11.2 (0.39-57.4) years at treatment initiation were stratified into three groups based on their treatment outcomes, i.e., those exhibiting clinically significant improvement (N = 41), those with non-clinically significant improvement (N = 18), or those showing no improvement (N = 40). Fifteen months after treatment, the initiation patients or patients' caregivers were assessed using a patient-rated scoring system based on the Patient Global Impression of Change (PGIC) scale, comprising 22 questions targeting important aspects and tasks in the daily life of patients with SMA. Results: We found no statistical difference in the patient perception of treatment benefits in 17 out of 22 domains across patient groups. Conclusions: Our results suggest that functional motor scales do not recapitulate patients' and patients' caregivers' experience of the effect of nusinersen treatment in SMA.

Department for Pediatric Neurology University Children's Hospital University Medical Centre Ljubljana Bohoričeva 20 1525 Ljubljana Slovenia

Department of Development and Regeneration KU Leuven 3000 Leuven Belgium

Department of Paediatric Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital 150 06 Praha Czech Republic

Department of Paediatrics University Hospitals Leuven 3000 Leuven Belgium

Division of Child Neurology Reference Center for Neuromuscular Diseases Department of Paediatrics University Hospital Liege and University of Liege 4000 Liege Belgium

John W Day Lab Department of Neurology and Neurological Sciences University of Stanford Stanford CA 94305 USA

MDUK Oxford Neuromuscular Centre Department of Paediatrics University of Oxford Oxford OX3 9DU UK

Neuromuscular Reference Center and Department of Paediatric Neurology Hôpital Universitaire des Enfants Reine Fabiola HUB Université Libre de Bruxelles 1020 Brussels Belgium

NMRC UZ Gent Ghent University Hospital 9000 Ghent Belgium

Paediatric Center Semmelweis University 1083 Budapest Hungary

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