Research Finds Significantly Higher Risk of Mortality in Patients With AS Before Approval of Nuusinersen
Based on data from more than 5,000 patients with spinal muscular atrophy (SMA) and 50,000 controls of the same age, patients with SMA had an almost 1.8-fold higher death rate.
Prior to the approval of nusinersen in 2016, patients with spinal muscular atrophy (SMA) of all ages and types had a higher risk of all-cause mortality compared to healthy patients of the same age. according to the results of a new study published in Neurology and therapy.
The researchers used data from the United States’ Optum anonymized electronic health records database from January 1, 2007 to December 22, 2016, which represents a period prior to the approval of nusinersen in the United States. Among patients with AMS, approximately 12% were under 13 years of age when they were first diagnosed with AMS and 31% were over 60 years of age. The majority were men (50.3%), non-Hispanics (80%) and whites (77%).
Based on data from over 5,000 patients with ASM and 50,000 controls of the same age, patients with ASM had a death rate nearly 1.8 times higher. During the follow-up period, 15% of patients with AMS died compared to 8.3% of patients in the control group. The increased mortality rate was observed in all age groups, including older patients, and in patients with type 3 SA (all-cause mortality, 1059 vs 603 per 100,000 patients- years). However, the researchers noted that in the latter group, the risk ratio did not reach statistical significance.
“This finding suggests that in the pre-treatment era, AS patients of all ages have a higher death rate than the general population, including older patients who survive to adulthood and those with type III AS, “the researchers explained, noting that their real-world results from a large US database are among the first to detail comparative mortality patterns between patients with the disease and those who don’t.
Among all patients with ADS, the overall all-cause mortality rate was 1,926 per 100,000 patient-years, compared to 1,099 per 100,000 patient-years for controls. The researchers noted that the death rate among study controls was similar but slightly higher than the rate reported by the CDC in the general population. The higher rate, they explain, may be due to differences in the age and gender distribution of study controls compared to the general population.
In their study, all-cause mortality was higher in men (2061 vs. 1233 per 100,000 patient-years) and women (1786 vs. 970 per 100,000 patient-years) with AS compared to controls.
In all age groups, the hazard ratio varied between 1.26 and 11.66. In the oldest age group, which included patients over 60 years of age, all-cause mortality was 3,476 compared to 2,788 per 100,000 patient-years for AS patients and controls, respectively.
“The greatest HR was observed in the age group under one year [HR 43.96 (95% CI 19.25–100.36)], which is not surprising given that these were mostly type I MSA patients, who have poor survival when left untreated, ”the researchers pointed out.
Some of the limitations of the analysis include that SMA was defined by the use of diagnostic trouble codes, that there was a lack of information about the specific type of SMA, and that there was a lack of information. on the age at first diagnosis of SMA. However, the actual large sample of patients from various healthcare settings was a strength as there may be less selection bias.
“Going forward, it is recommended that mortality studies of patients with AMS include detailed analysis of the cause of death and genetic confirmation of AMS, which will provide detailed mortality rates in clinical studies.” and will elucidate the potential reason for higher mortality in patients with AMS, “the authors concluded.
Viscidi E, Juneja M, Wang J, et al. Comparative all-cause mortality in 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