Comparison of Nusinersen Monotherapy Versus Combination Therapy With Nusinersen and Onasemnogene Abeparvovec in Spinal Muscular Atrophy Type 1 Patients With Two SMN2 Copies: A Multicenter Study From Türkiye.

Abstract

Introduction/aims: Data comparing nusinersen monotherapy with combination therapy using nusinersen and onasemnogene abeparvovec (OA) in spinal muscular atrophy (SMA) type 1 patients are limited. This study aimed to compare the clinical outcomes of nusinersen monotherapy versus combination therapy (nusinersen and OA) in SMA type 1 patients with two SMN2 copies.

Methods: This retrospective multicenter study included 82 patients divided into nusinersen monotherapy (n = 42) and combination therapy (n = 40) groups. Outcomes included motor milestones, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores, respiratory and nutritional status, and survival. Patients were stratified by age at treatment initiation (≤ 3, 3-6, and > 6 months). An age-matched subgroup analysis was performed.

Results: Age at treatment initiation, total administered nusinersen doses, and follow-up duration were comparable between groups. All deaths (n = 8) occurred in the monotherapy group among patients who initiated treatment after 3 months of age (p = 0.005). There was no significant difference between groups in the age at achieving unsupported sitting. In the age-matched subgroup analysis (n = 44, 22 per group), no significant differences were found between monotherapy and combination therapy in terms of motor function, CHOP-INTEND progression, respiratory and feeding status. Earlier treatment was associated with better feeding outcomes (OR: 0.740, p = 0.024). Pre-treatment respiratory and feeding status were also predictive of corresponding outcomes.

Discussion: Early treatment is the main determinant of outcomes, while combination therapy shows no clear advantage over monotherapy. Larger prospective studies are needed to clarify the role and timing of combination therapy.