Introduction: Given the lifelong progression of spinal muscular atrophy (SMA), understanding the long-term effects of nusinersen treatment is crucial. Prior systematic literature reviews (SLRs) consolidated evidence on the real-world effectiveness of nusinersen in adolescents and adults; however, the publications included in these reviews had a limited follow-up of 10-14 months. As newer publications with longer follow-up and more diverse groups have emerged, we conducted an updated SLR and meta-analysis to evaluate the long-term effectiveness of nusinersen treatment in adolescents and adults across a broad spectrum of SMA.
Methods: The updated SLR included papers published from July 1, 2022 (previous search date) to August 4, 2024 with ≥ 5 individuals ≥ 13 years of age and with ≥ 6 months' data on ≥ 1 selected motor function outcome (Hammersmith Functional Motor Scale-Expanded [HFMSE], Revised Upper Limb Module [RULM], and Six-Minute Walk Test [6MWT]). Changes in motor function after initiating nusinersen were summarized across studies included in the previous and updated SLR. Effect sizes were pooled using random-effects models in the meta-analysis. To understand treatment effects by disease severity, a subgroup meta-analysis by ambulatory status was conducted.
Results: Seventeen publications including 650 individuals from 16 countries followed up to 57 months met the inclusion criteria for the updated SLR. Individuals ranged in age from 13 to 71 years, and approximately 40% were ambulatory. Mean or median improvements or stability in motor function over the follow-up period were consistently reported across 31 studies (including 14 from a previous SLR) over 4 years. In the meta-analysis, statistically significant increases from baseline were observed in all three motor function outcomes. Mean HFMSE improvements were greater among ambulant individuals, while mean RULM improvements were greater among non-ambulant individuals.
Conclusion: Our findings demonstrate the long-term effectiveness of nusinersen in many adolescents and adults from a diverse SMA population, which could support informed decision-making in clinical practice.
Keywords: Adolescents; Adults; Effectiveness; Long-term; Motor function; Nusinersen; Spinal muscular atrophy.
People living with spinal muscular atrophy (SMA) produce less survival motor neuron (SMN) protein, leading to motor neuron damage and reduced motor function over time. Nusinersen is an approved treatment for SMA that works by increasing the levels of SMN protein made in the body. Since SMA is a lifelong genetic condition, it is important to understand the long-term effects of nusinersen treatment, especially in adolescents and adults who are underrepresented in clinical trials. We reviewed the scientific literature to find information (published between July 1, 2022 and August 4, 2024) on how effective nusinersen is in treating adolescents and adults with SMA. We found 17 studies that included data on 650 people with SMA from 16 countries, aged 13–71 years. Approximately 40% of these people with SMA were able to walk, and many studies had collected data for over 2 years after these people had started nusinersen treatment. A previous search of the literature up to July 1, 2022 had found 14 studies on how effective nusinersen is in adolescents and adults, but data in these studies had only been collected for 10–14 months after starting nusinersen treatment in most people. We considered data from all 31 studies to provide a more thorough assessment of how effective nusinersen is in adolescents and adults. These data suggest that many individuals from a diverse SMA population experience improved or stable motor function over a 4-year period. This information may help patients, caregivers, clinicians, and policymakers to make informed decisions.
© 2025. The Author(s).