nusinersen and Fatigue

Ambulatory individuals with spinal muscular atrophy (SMA) experience muscle weakness, gait impairments, and fatigue that affect their walking ability. Improvements have been observed in motor function in children treated with nusinersen, but its impact on fatigue has not been studied.. Post hoc analyses were used to examine changes in 6-minute walk test (6MWT) distance and fatigue in children and adolescents with SMA type II and III who received their first dose of nusinersen in the phase Ib/IIa, open-label CS2 study and were ambulatory during CS2 or the extension study, CS12.. Fourteen children performed the 6MWT. Median (25th, 75th percentile) distance walked increased over time by 98.0 (62.0, 135.0) meters at day 1050, whereas median fatigue changed by -3.8% (-19.7%, 1.4%).. These results support previous studies demonstrating clinically meaningful effects of nusinersen on motor function in children and adolescents with later-onset SMA.

Topics: Adolescent; Child; Child, Preschool; Fatigue; Female; Humans; Infant; Male; Muscular Atrophy, Spinal; Oligonucleotides; Walk Test

Few studies assessed the effect of nusinersen on respiratory function in adult patients with spinal muscular atrophy (SMA). The aim of this single-center study was to analyze pulmonary function and its association with muscle function and quality of life (QoL) in adult patients with 5q-SMA under nusinersen.. We recorded forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF) during nusinersen treatment in 38 adult SMA patients. Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), 36-Item Short Form Health Survey (SF-36) questionnaire and Fatigue Severity Scale (FSS) were recorded and correlations between muscle function, QoL, fatigue and respiratory parameters were analyzed.. No differences were detected between mean FVC, FEV1, PEF at different timepoints versus baseline. Ambulatory patients showed significant improvement in mean PEF at month 30, compared to non-ambulatory patients (+ 0.8 ± 0.5 vs. - 0.0 ± 0.5, p < 0.05). Patients with fatigue at baseline showed significant improvement in mean PEF at month 10, compared to patients without fatigue at baseline (+ 0.6 ± 0.9 vs. - 0.4 ± 0.5, p < 0.05). Physical domains of SF-36 positively correlated with the change in FVC and FEV1. FSS negatively correlated with the change in mean PEF.. Mean pulmonary function remained stable during nusinersen treatment over a period of up to 30 months. Improvement in pulmonary function was associated with improvement in motor function, fatigue and QoL, early after nusinersen initiation.

Topics: Adult; Cohort Studies; Fatigue; Humans; Muscular Atrophy, Spinal; Quality of Life; Spinal Muscular Atrophies of Childhood

Topics: Aged; Fatigue; Humans; Muscular Atrophy, Spinal; Oligonucleotides; Walking

5q-Associated spinal muscular atrophy is a hereditary neuromuscular disease leading to progressive muscle weakness in which fatigue occurs and affects quality of life. Treatment with the antisense oligonucleotide nusinersen has been shown to improve motor function. Fatigue can be measured within the Fatigue Severity Scale (FSS). FSS is a self-reported questionnaire consisting of nine items to quantify fatigue severity within the last week. Higher values indicating a higher severity. Using the FSS, fatigue was measured in 28 adult patients, subdivided into ambulatory and non-ambulatory, suffering from a genetically confirmed 5q-SMA under treatment with nusinersen in accordance with the label. Correlations were performed among FSS and motor scales, 6-minute walk test (6MWT) and Hammersmiths Functional Motor Scale Expanded (HFMSE). Evaluation was performed prior to treatment initiation and after 6 and 10 months. The mean FSS score for all 28 patients at baseline was 4.61 ± 1.44. After 6 months mean FSS score significantly reduced to 3.92 ± 1.35. After 10 months mean FSS score had not differed from baseline, 3.84 ± 1.25. A moderate negative correlation of the difference of FSS and 6MWT after 6 months compared to baseline conditions was measured. Nusinersen reduces fatigue as measured by the FSS in adult patients with 5q-SMA transiently after initiation of treatment. There was no reduction of FSS 10 months after the beginning of treatment when compared to baseline.

Topics: Adult; Fatigue; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscular Atrophy, Spinal; Oligonucleotides; Prognosis; Survival of Motor Neuron 1 Protein; Walk Test; Young Adult