The new report is based on real-world data from a patient registry and shows some patients even regain motor function under treatment with nusinersen for spinal muscular atrophy (SMA).
A new registry-based study of more than 250 children with spinal muscular atrophy (SMA) types 2 and 3 shows that new disease-modifying therapies are having a meaningful impact on disease progression.
The study, based on a follow-up period of up to 38 months, shows the therapies have results in real-world use that are similar to those in clinical trials. The report was published in the Orphanet Journal of Rare Diseases.
SMA is a rare, neuromuscular disease in which patients experience proximal and progression muscle weakness associated with the homozygous deletion of survival motor neuron 1 (SMN1) gene on chromosome 5. The disease is categorized based on the age of onset and the physical milestones a patient is expected to reach.
People with type 2 and type 3 SMA are typically diagnosed after 6 months of age. Those with type 2 SMA are expected to achieve unassisted sitting, but never gain the ability to walk. Those with type 3 SMA are able to walk unassisted.
Corresponding author Astrid Pechmann, MD, of the University of Freiburg, in Germany, and colleagues, explained that a trio of disease-modifying therapies for SMA have been approved in the United states and Europe over the past 5 years, including nusinersen (Spinraza), onasemnogene abeparvovec (Zolgensma), and risdiplam (Evrysdi). In clinical trials, nusinersen improved motor function in children for a follow-up period of 15 months, but Pechmann and colleagues said longer-term, real-world data on the efficacy of nusinersen and similar therapies is limited.
The authors therefore looked at the SMArtCARE registry, a database that aims to include all people in Germany, Austria, and Switzerland who have SMA, regardless of their age, disease severity, or treatment regimen. For the purposes of the current study, investigators focused on non-ambulant patients with type 2 or 3 SMA who were treated with nusinersen and were under the age of 18 when they began treatment. Nusinersen was the first SMA therapy approved in Europe, and thus it is the therapy for which the longest-term data are available.
They found a total of 256 people with type 2 or 3 SMA who met those criteria. The investigators then used 2 scales—the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM)—to track patient progress.
The data showed that about one-third of patients (32.4%) experienced clinically meaningful improvements in upper limb motor function based on the RULM scale, though the number was somewhat lower (24.6%) using the HFMSE.
No patients lost a motor function milestone, but 8.6% of patients gained a new motor milestone. Few patients saw their conditions worsen in a clinically meaningful way (4.3% of patients according to HFMSE and 1.2% of patients according to RULM).
Even though many patients did not record improvements in motor function, Pechmann and colleagues noted that when left untreated, people with SMA experience continual progression of muscle weakness.
“Thus, a stabilization of disease status can already be considered as a positive response to treatment,” they wrote.
Though nusinersen appeared to improve patients’ motor function, the authors said it did not appear to have an effect on the likelihood that a patient needed non-invasive ventilator support or tube feeding.
Pechmann and colleagues said their study is subject to the same limitations or any real-world study, including a lack of data for certain patients at certain time points and differing levels of data quality due to the wider range of health care professionals tracking patients.
Still, the authors said these data show that drugs like nusinersen have significantly changed outcomes for people with SMA.
“[O]ur results demonstrate improvements or stabilization of disease progression in most non-ambulant children with SMA type 2 or type 3 under nusinersen treatment,” they wrote.
Pechmann A, Behrens M, Dörnbrack K, et al. Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study. Orphanet J Rare Dis. Published online October 23, 2022. doi:10.1186/s13023-022-02547-8