Nusinersen treatment in adults with severe spinal muscular atrophy
Résumé
Background and objectives: Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN 1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies. Methods: We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018–2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was < or ≥ the mean (15.6%). Adverse events were recorded. Results: We identified 18 patients who received 4 to 8 Nusinersen injections. No significant improvements occurred over time in any of the MFM scores or lung function test results, which did not differ between groups. The COPM performance score improved significantly from day 0 to day 303 in the high-MFM group and the COPM satisfaction score in the overall population from D0 to D183. Half the patients achieved the minimal clinically important difference for both COPM scores. Discussion: The overall stability of conventional motor assessment in this population with advanced disabilities is encouraging to use more sensitive tools based on self-perception and autonomy in daily life activities, such as COPM. Our finding of a significant COPM performance score improvement from days 0 to 303 only in the patients with initial MFM-32 scores above the mean in the population suggests that the severity of the baseline disabilities may affect treatment efficacy. Classification of evidence level: IV, retrospective observational cohort study.