Researchers investigated the mid- and long-term clinical outcomes of patients with spinal muscular atrophy (SMA) on nusinersen, onasemnogene abeparvovec, risdiplam, or combination therapies, and found that large amounts of data were missing, hampering their ability to adequately compare the drugs, as published in the European Journal of Pediatric Neurology.

The introduction of disease-modifying therapies in the last few years has revolutionized SMA treatment. Nusinersen is an SMN2 splicing modifier and onasemnogene abeparvovec is a form of gene therapy. Risdiplam is the most recent drug to be approved by the European Medicine Agency for the treatment of SMA. 

Erdos and Wild set out to conduct a systematic review of these SMA therapies with at least 12 months of follow-up. They aimed to characterize the efficacy and safety of these therapies using published real-world study data.

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They conducted a systematic literature search on 5 academic databases, including all types of patients with SMA, all 3 drugs mentioned (or a combination of them), and effectiveness or safety reports of these drugs with at least 12 months of follow-up.

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Out of the 538 articles identified in the database, only 22 studies met the inclusion criteria. A total of 19 assessed nusinersen, 1 assessed onasemongene abeparvovec, and 2 assessed the combination of nusinersen and onasemnogene abeparvovec. Erdos and Wild found no article on risdiplam that met the inclusion criteria. 

“Heterogeneity in the reported outcomes, the length of follow-up and the chosen outcome measures across studies are major concerns, often acknowledged by study authors themselves, and hamper comparability of study results,” Erdos and Wild wrote. “Long-term clinical data published by independent clinicians are lacking.”

Although the overall picture of these studies suggests that disease-modifying therapies confer a striking contrast to the natural progression of the disease in patients with SMA, the researchers recommended that periodic assessments of patient outcomes be conducted over many years for physicians to understand the long-term benefit of these drugs.


Erdos J, Wild C. Mid- and long-term (at least 12 months) follow-up of patients with spinal muscular atrophy (SMA) treated with nusinersen, onasemnogene abeparvovec, risdiplam or combination therapies: a systematic review of real-world study data. Eur J Paediatr Neurol. Published online April 30, 2022. doi:10.1016/j.ejpn.2022.04.006