Nusinersen Linked With Modest Improvements in Adult SMA

The patients, from 5 referral centers, were followed for at least 6 months and showed modest improvements in both motor and functional scales when treated with the antisense oligonucleotide for spinal muscular atrophy (SMA).

Treatment with nusinersen is associated with some improvements in disease severity for certain adult patients with spinal muscular atrophy (SMA), according to recent a study, which found that patients with more severe disease are less likely to see improvements.

Findings came from a group of 79 patients with 5q SMA aged older than 15 years, 39 of which received nusinersen. The patients, from 5 referral centers, were followed for at least 6 months and showed modest improvements in both motor and functional scales when treated with the antisense oligonucleotide.

After 6 months of treatment, patients showed significant improvements in Revised Upper Limb Module (RULM) compared with untreated patients, with an improvement of 2 points (+0.46). By the last visit at 16 months, treated patients had significant improvements in Hammersmith Functional Motor Scale Expanded (HFMSE) (OR = 1.15; 95% CI, 1.04-1.27, P = .006) and their 6-minute walk test (6MWT) (OR = 1.07; 95% CI, 1.06-1.08, P < .001). Functional scores were also improved at 16 months as assessed by EgenKlassification (EK2) (OR = 0.81; 95% CI, 0.71-0.92, P = .001).

“Overall, the effect of treatment in motor scales, as shown in our models, seems to be modest, in line with previous studies. Interestingly, the greatest effect was found in EK2, a bedside functional scale for the assessment of non-ambulant patients,” wrote the researchers. “This could reflect its ability to detect mild functional changes in non-ambulant patients and to measure the effect of nusinersen on fatigability, which might not be captured by HFMSE and RULM. However, direct comparisons between scales should be interpreted with caution because not all scales are applicable to the same patients.”

Treated patients were more likely to experience clinically meaningful improvements across all scales, though the researchers noted that differences were only statistically significant for EK2, RULM, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale.

Clinical and patients’ global impression of change (CGI-C and PGI-C) were recorded at the last visit at 16 months. There were 2 patients with SMA type 3a that achieved a CGI-C of 3, indicating very much improved. One patient, with 4 SMN2 copies, was a sitter who was able to stand still with help; after 14 months of treatment, she improved 20 points in HMFSE, 10 points in RUFLM, and was able to walk independently for 30 meters in the 6MWT—a benchmark considered clinically meaningful. The second patient, who had 3 SMN2 copies and was close to losing ambulation before initiating treatment, improved 24 points in HFMSE, 7 points in RULM, and 183 meter in 6MWT after 14 months of treatment.

Multivariable assessment showed that walkers and longer time on treatment were associated with a better response, as determined by CGI-C.

“It has been claimed that the mild improvements found in the adult SMA population after nusinersen treatment could be due to a placebo effect. Whilst a placebo effect might indeed explain some improvements, increasing evidence also supports a physiological effect of nusinersen,” wrote the researchers.” First, most reports show consistent positive results. Secondly, although most patients in our study experience only mild improvements, about 25% of them experienced moderate or even remarkable improvements. In a neurodegenerative disease, any strong improvement is unexpected and is hardly explained by a placebo effect. Thirdly, longer treatment duration was associated with greater response in our and previous studies.”

Adverse events were common but mild among patients receiving nusinersen, with 77% experiencing at least 1 adverse event during the study period. Of the 55 events, 45 were mild and 10 were moderate. Mild adverse events included post lumbar puncture syndrome and back pain, and moderate adverse events included post lumbar puncture syndrome, urinary retention due to neurogenic bladder, and radial neurapraxia.

There were 2 (5%) patients who discontinued treatment due to an adverse event and 1 patient who discontinued due to repeated post lumbar puncture syndrome.


Vázquez-Costa J, Povedano M, Nascimiento-Osorio A, et al. Nusinersen in adult patients with 5q spinal muscular atrophy: A multicenter observational cohorts' study. Eur J Neurol. Published online July 24, 2022. doi:10.1111/ene.15501

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