Nonadherence to Nusinersen Treatment Increases Health Care Utilization, Costs in SMA

Results of a retrospective claims database analysis suggest that adherence to scheduled intrathecal nusinersen injections may lead to improvements in comorbidities, health care utilization, and costs for spinal muscular atrophy (SMA) types 1, 2, and 3.

Nusinersen, an antisense oligonucleotide, was the first disease-modifying therapy approved for the treatment of spinal muscular atrophy (SMA), but real-world data on patient adherence to the standard regimen of intrathecal injections are limited. A retrospective claims database analysis published in Advances in Therapy aimed to assess nusinersen adherence and the impact of nonadherence on SMA-related comorbidities, health care resource utilization (HCRU), and costs.

The standard nusinersen treatment regimen includes lifelong intrathecal injections every 4 months following a 4-injection loading phase, and both early treatment initiation and continued adherence to treatment are key aspects of positive outcomes. To gauge treatment adherence in patients with SMA types 1, 2, and 3, study authors conducted an analysis of insurance claims from December 23, 2016, when nusinersen was first approved by the FDA, to November 20, 2019.

They identified for the analysis patients who had completed the loading phase: 23 patients with type 1 SMA (SMA1), the most severe in the study group; 41 patients with type 2 SMA (SMA2); and 260 patients with type 3 SMA (SMA3).

Researchers utilized Symphony Health’s Integrated Dataverse, a longitudinal patient database that includes prescription claims, HCRU, and costs across the United States. This data bank covers all forms of payment, including commercial insurance plans, Medicare Part D, Medicaid, and other assistance programs. Patients were followed from the start of treatment with nusinersen until last observed clinical activity or until no more data were available.

In the real-world setting, most patients received at least 1 dose outside of the scheduled intervals. Even with a grace period of 7 days off schedule for loading phase doses and 14 days for maintenance injections, 56.5% of SMA1 patients, 73.2% of SMA2 patients, and 60.8% of SMA3 patients received off-schedule doses.

Across all SMA phenotypes, nonadherence was associated with greater comorbidities related to SMA, such as difficulty with feeding, dyspnea, respiratory anomalies, and muscle weakness. More neurodevelopment disorders, sleep-wake disorders, and chronic pulmonary disease were also seen in nonadherent patients.

After 12 months of treatment, persistence rates were similar across types. SMA1 patients had a 55.2% rate of persistence; SMA2 patients, 42.4%; and SMA3 patients, 54.6%. Median time to discontinuation was 18.5 months for SMA1, 6.2 months for SMA2, and 14.4 months for SMA3. Regardless of subtype, less than 50% of patients continued treatment past 24 months.

Stopping treatment was associated with greater HCRU, defined as incident rates per patient per year (PPPY), and calculated as the number of events divided by the number of years of observation. Health care costs were also greater.

Nonadherent patients with SMA type 1 had 48.4 HCRU days PPPY vs 42.2 in adherent patients. In SMA2 patients, there were 109.6 HCRU days PPPY for those who were nonadherent vs 45.2 for adherent patients; and for SMA3 patients, 71.7 vs 54.8 days. Across the board, costs were higher in nonadherent vs adherent patients (not including nusinersen costs). On average, patients who discontinued treatment had greater total health care costs (not including nusinersen costs) than those who continued.

Overall, the available data suggest that adherence to nusinersen treatment is important to reduce HCRU and costs, as well as improve outcomes, in patients with SMA treated with nusinersen. The authors conclude that more research is needed to assess the effects of adherence vs nonadherence as the number of patients who have received nusinersen grows.


Gauthier-Loiselle M, Cloutier M, Toro W, et al. Nusinersen for spinal muscular atrophy in the United States: findings from a retrospective claims database analysis. Adv Ther. Published October 28, 2021. doi:10.1007/s12325-021-01938-w