Research Highlights Significantly Higher Risk of Mortality Among Patients With SMA Prior to Nusinersen Approval

Based on the data from over 5000 patients with spinal muscular atrophy (SMA) and 50,000 age-matched controls, patients with SMA had a nearly 1.8-fold higher mortality rate.

Before the approval of nusinersen in 2016, patients with spinal muscular atrophy (SMA), regardless of age and SMA type, had a higher risk of all-cause mortality compared with healthy patients of the same age, according to new study findings published in Neurology and Therapy.

The researchers used data from the US Optum electornic health record de-identified database from January 1, 2007 to December 22, 2016, which represents a time period prior to the approval of nusinersen in the United States. Among the patients with SMA, approximately 12% were younger than 13 years at their first diagnosis of SMA and 31% were older than 60 years. The majority were male (50.3%), non-Hispanic (80%), and White (77%).

Based on the data from more than 5000 patients with SMA and 50,000 age-matched controls, patients with SMA had a nearly 1.8-fold higher mortality rate. During the follow-up period, 15% of patients with SMA died compared with 8.3% of patients in the control group. The increased rate of mortality was seen across all age groups, including older patients, and in patients with SMA type 3 (all-cause mortality, 1059 vs 603 per 100,000 patient years). However, the researchers noted that in the latter group, the hazard ratio did not reach statistical significance.

“This finding suggests that, in the pre-treatment era, SMA patients of all ages have a higher mortality rate than the general population, including older patients who survive into adulthood and those with SMA type III,” explained the researchers, noting that their real-world findings from a large US database are among the first to detail comparative mortality patterns among patients with the disease and those without.

Among all patients with SMA, the overall all-cause mortality rate was 1926 per 100,000 patient years, compared with 1099 per 100,000 patient years for the controls. The researchers noted that the mortality rate among controls in the study was similar but slightly higher than the CDC’s reported rate among the general population. The higher rate, they explain, may be due to differences in the age and gender distribution of the study controls compared with the general population.

In their study, all-cause mortality was higher for both males (2061 vs 1233 per 100,000 patient years) and females (1786 vs 970 per 100,000 patient years) with SMA compared with controls.

Across age groups, the hazard ratio ranged between 1.26 and 11.66. In the oldest age group, which included patients over the age of 60, all-cause mortality was 3476 vs 2788 per 100,000 patient years for patients with SMA and controls, respectively.

“The largest HR was observed in the <1 year age group [HR 43.96 (95% CI 19.25–100.36)], which is not surprising given that these were mostly patients with SMA type I, who have poor survival when untreated,” emphasized the researchers.

Some of the limitations of the analysis include that SMA was defined through the use of diagnostic codes, there was a lack of information about specific SMA type, and there was a lack of information on the age at first diagnosis of SMA. However, the large, real-world sample of patients from diverse medical care settings was a strength bceause there may be less selection bias.

"In the future, it is recommended that mortality studies of patients with SMA include a detailed analysis of cause of death and genetic confirmation of SMA, which will provide detailed mortality rates in clinical studies and elucidate the potential reason for higher mortality in SMA patients," the authors concluded.


Viscidi E, Juneja M, Wang J, et al. Comparative all-cause mortality among a large population of patients with spinal muscular atrophy versus matched controls. Neurol Ther. Published online December 22, 2021. doi:10.1007/s40120-021-00307-7