Use of the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) in Spinal Muscular Atrophy

Background: Spinal muscular atrophy (SMA) has a remarkable impact on function and participation. Subsequently, the caregivers of individuals with SMA are impacted as well. Providers and the SMA community should be aware of the presence of and likely expectations for the existence of caregiver burden. Methods: The Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) quantifies caregivers’ perceptions of function and quality of life pertaining to time, finance and emotion. Analyses were conducted among SMA types and ambulatory and ventilatory status. Participants with SMA had varying ranges of function and were on pharmaceutical treatment. Total ACEND score, longitudinal change in total ACEND score, total quality of life (QOL) score, change in total QOL score and subdomains for QOL, including time, emotion and finance, were all explored. Results: Overall, the ACEND demonstrated discriminant validity and some observed trends. Total ACEND scores improved for caregivers of those with SMA 2, remained stable longitudinally for caregivers of those with SMA 1 and 3 and were not influenced by ventilation status. The caregivers of individuals with SMA 1 had the lowest total quality of life (QOL) score, as did the caregivers of non-ambulatory individuals and those requiring assisted ventilation. Longitudinally, there were no changes in total QOL between caregivers of individuals with different SMA types or ambulatory or ventilation status. There were some differences in emotional needs, but no differences in financial impact between the caregivers of individuals with different types of SMA or ambulatory and ventilatory status. Conclusions: With this information enlightening the presence of caregiver burden and expected changes in burden with pharmaceutical treatment, providers, third party payors and the SMA community at large can better assist, equip and empower those providing the necessary assistance to enable the lives of those with SMA

Functional outcome measures in young, steroid-naïve boys with Duchenne muscular dystrophy.

The purpose of this study was to quantitate motor performance in 196 genetically confirmed steroid-naïve boys with Duchenne muscular dystrophy (DMD), to evaluate the test-retest reliability of measures of motor performance in young DMD boys, and to assess correlations among the different functional outcomes including timed tests. Boys aged 4-7 years were recruited in the FOR-DMD study, a comparative effectiveness study of different steroid regimens in DMD. Eligible boys had to be able to rise from the floor independently and to perform pulmonary function testing consistently. The boys were evaluated with standardized assessments at the screening and baseline visits at 32 sites in 5 countries (US, UK, Canada, Italy, Germany). Assessments included timed rise from floor, timed 10 m walk/run, six-minute walk distance, North Star Ambulatory Assessment (NSAA) and forced vital capacity (FVC). Mean age at baseline was 5.9 years (range 4.1-8.1 years). Test-retest reliability was high for functional assessments, regardless of time lag between assessments (up to 90 days) and for the majority of age groups. Correlations were strong among the functional measures and timed tests, less so with FVC. Physiotherapy measures are reliable in a young, steroid-naïve population and rise from floor velocity appears to be a sensitive measure of strength in this population

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

International audienceBACKGROUND Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2: 1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (>= 3 points), an outcome that indicates improvement in at least two motor skills. RESULTS In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P< 0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P< 0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials. gov number, NCT02292537.