Study: Nusinersen Continues to Improve Motor Function in SMA in Second Year of Treatment

Real-world data are suggesting that nusinersen continues to yield improvements for patients with spinal muscular atrophy (SMA) in their second year of treatment, according to results published in Annals of Clinical and Translational Neurology.

With various treatments now available for patients with the disease, and the option to switch between these treatments, the researchers argue that their findings help add clarity to possible differences in the changes patients could experience when switching or adding on a treatment.

“Even in the absence of published evidence, many families, even if partially satisfied with the results of one drug, often opt to add/switch to a different treatment with the hope to see additional efficacy,” explained the group. “This has reduced the possibility to understand long-term efficacy and safety profiles of individual drugs. There are very few long-term longitudinal data using the individual drugs and most of them are related to the long-term follow-up of clinical trial cohorts in type 1 infants. Less has been reported in type 2 and 3 patients.”

The longitudinal data coming from the new study included findings from 46 patients with type 2 SMA and 65 patients with type 3 SMA, all of whom had not received previous treatment before receiving nusinersen for at least 24 months. Using both the Hammersmith Functional Motor Scale (HFMSE) and Revised Upper Limb Module (RULM), the researchers observed that improved motor function among patients continued after 12 months and during the second year of treatment.

Improvements, explained the researchers, were mainly driven by younger patients, with smaller improvements seen in older patients.

For both subtypes, there were no significant differences between treated and untreated patients at baseline based on both measurement tools. By 1 year of treatment and continuing through 2 years of treatment, significant differences between groups were evident.

The difference between treated and untreated patients with SMA 2 was significant on both HFMSE and RULM at 12 months (P < .001 and P = .008, respectively) and at 24 months (P < .001 and P < .001).

For those with SMA type 3, there was also a significant difference between the treated and untreated patients on the HFMSE and RULM at 12 months (P = .0002 and P < .001), but at 24 months only the difference on HFMSE was significant (P = .0002 and P = .9225).

“The comparison showed a consistent difference between treated and untreated patients,” the researchers wrote. “This held true not only in the age subgroups in whom there was the most obvious therapeutic response, such as type 2 younger than 5 years, but also in those subgroups in whom there was an apparent small change after treatment that became meaningful when compared to the marked decline found in the untreated patients of the same age and functional level.”

Using HFMSE, which showed more obvious improvement, the researchers found that patients with type 2 SMA experienced significant improvements from baseline within the first 12 months and both subgroups of patients experienced significant improvements in the second year. In patients with type 2 SMA, improvements were significant in the second year of treatment for sitters, and in patients with type 3 SMA, improvements were significant in ambulant patients.

With RULM, improvements were less prominent, with type 2 patients experiencing significant improvements from baseline in both the first and second year and type 3 patients experiencing no significant improvements at any point. The researchers note that this could be partly attributed to the “ceiling effect” typically seen in ambulant patients, in whom HFMSE is more sensitive. Similar to HFMSE findings, patients with type 2 SMA who were sitters showed significant improvements as measured by RULM in the second year of treatment. Among patients with type 3 SMA, neither ambulant nor nonambulant patients showed significant improvements.

The study authors noted that using real-world data to compare improvements during treatment vs the available data on the progress of untreated patients can help to establish realistic expectations for the effect of treatment and “to better identify responders in patients of different age and functional level.”

Reference

Pane M, Coratti G, Pera M, et al. Nusinersen efficacy data for 24-month in type 2 and 3 spinal muscular atrophy. Ann Clin Transl Neurol. Published online February 15, 2022. doi:10.1002/acn3.51514