Matched-pair analysis of motor outcomes in adults with spinal muscular atrophy on nusinersen vs. risdiplam

TL;DR

This study compared two SMA treatments, nusinersen and risdiplam, in adults and found both similarly maintained motor function over three years.

Contribution

First matched-pair real-world comparison of nusinersen and risdiplam in adult SMA patients.

Findings

Both nusinersen and risdiplam stabilized motor function over nearly three years.

No significant differences were observed in motor score trajectories between the two treatments.

Baseline characteristics were balanced between matched groups.

Abstract

Nusinersen and risdiplam are approved disease-modifying therapies for adults with 5q-associated spinal muscular atrophy (SMA). To date, no direct comparison of the two treatments in adults has been conducted. Real-world cohorts of nusinersen and risdiplam differ in key baseline characteristics, such as motor function and disease severity, making direct comparison challenging. Nevertheless, such analyses are important for treatment decisions.

We conducted a single-center, prospective, matched-pair analysis of adult persons with SMA (pwSMA) treated with nusinersen or risdiplam between 2017 and 2025. Patients were matched 1:1 based on baseline motor scores (Hammersmith Functional Motor Scale-Expanded [HFMSE], Revised Upper Limb Module [RULM]) and adjusted for age and disease duration at treatment initiation. Motor function was assessed at baseline, 4–8, 10–14, 22–26, and 32–40 months after treatment initiation. Pairwise difference scores (Δ-values) were analyzed using non-parametric tests.

From a cohort of 101 pwSMA (65 nusinersen, 36 risdiplam), 24 matched pairs (n = 48) were identified. Baseline demographic and clinical characteristics did not differ between groups. Over a maximum follow-up of nearly three years, no differences were observed in the trajectories of HFMSE or RULM scores between the nusinersen and risdiplam group. Within each group, motor function remained stable without significant decline.

In this first matched-pair comparison of nusinersen and risdiplam in adults with SMA, both treatments achieved similar stabilization of motor function over almost three years. Larger, multicenter studies are warranted to confirm these results and explore potential subgroup-specific treatment effects.

The online version contains supplementary material available at 10.1007/s00415-025-13589-w.

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