Long-term persistence, safety and effectiveness of nusinersen in spinal muscular atrophy: a population-based study

Autores de IIS La Fe

• Karolina Agata Aragon Gawinska

  Autor

• Nancy Carolina Ñungo Garzón

  Autor

• Nuria Muelas Gómez

  Autor

• Rafael Sivera Mascaró

  Autor

• 

  Teresa Sevilla Mantecón

  Autor

• Inmaculada Pitarch Castellano

  Autor

• Juan Francisco Vázquez Costa

  Autor

Participantes ajenos a IIS La Fe

• Hervas D.

Grupos

• Patología Neuromuscular y Ataxias

Abstract

Background and objective: Nusinersen was the first disease-modifying treatment approved for spinal muscular atrophy (SMA). However, long-term results of broad unselected populations—particularly adolescents and adults—remain limited. We aimed to evaluate nusinersen long-term persistence and effectiveness in a population-based cohort. Methods: We conducted a population-based, ambispective observational study of all SMA patients in the Valencian community (Spain) between 2017 and 2022, with follow-up until December 2025 or censoring (due to death, clinical trial, or treatment switch). Demographic, clinical, and motor outcomes using revised SMA Functional Composite Score (SMA-FCR) were collected. Patients were classified as responders or non-responders. Nusinersen discontinuation risks and motor trajectories were evaluated using Bayesian linear and mixed linear models. Results: Of 72 patients included, 18 were < 12 years old (all treated with nusinersen) and 54 were = 12 years (28 treated; 26 untreated) at the baseline visit. After a median follow-up of 4.6 years until censoring, all children were found responders, compared with 68% of those = 12 years. Discontinuation rates were 11% in children compared to 75% in the older cohort. In patients = 12 years, reasons for discontinuation included: treatment burden (71%), and loss (53%) or lack of benefit (43%). Lower baseline SMA-FCR (expEstimate = 0.84 [0.718,0.93],prob:1) and older age (expEstimate = 1.028 [1.011,1.055],prob:1) independently predicted higher discontinuation risk. Sustained treatment was associated with SMA-FCR increase, while untreated and discontinued patients showed slight deterioration. Discussion: Nusinersen persistence was high in children but declined significantly after age 12 due to treatment burden and limited efficacy although a 25% of adolescents and younger adults with higher baseline function experienced sustained benefit. © The Author(s) 2026.

© 2026. The Author(s).

Keywords

• Adolescent; Adult; Child; Child, Preschool; Cohort Studies; Female; Follow-Up Studies; Humans; Infant; Male; Muscular Atrophy, Spinal; Oligonucleotides; Spain; Treatment Outcome; Young Adult; nusinersen; oligonucleotide; adolescent; adult; child; cohort analysis; drug therapy; female; follow up; human; infant; male; preschool child; Spain; spinal muscular atrophy; treatment outcome; young adult