Meaningful Activity Improvements Seen in SMA After Nusinersen

Individual items on RULM revealed meaningful improvements in participants from the SHINE and CHERISH studies.

Meaningful improvements in activities of daily living were observed in patients with spinal muscular atrophy (SMA) treated with nusinersen (Spinraza; Biogen) in the CHERISH (NCT02292537) and SHINE (NCT02594124) studies when looking at individual items on the Revised Upper Limb Module (RULM).

Data from the studies were presented at the 2023 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 19-22, in Dallas, Texas, by Jaqueline Montes, PT, EdD, Associate Professor of Rehabilitation and Regenerative Medicine, Columbia University Irving Medical Center.

“Assessing the abilities gained or lost in the individual items of the RULM can help with understanding clinically relevant changes in patients with SMA,” Montes and colleagues wrote in the poster.

The findings presented included 114 participants from CHERISH and SHINE that were followed up for 2.5 years (day 930) from baseline until the August 2019 data cut-off date. These participants were a mean 4.5 years (standard deviation, 1.7) of age at first nusinersen dose and 83 initiated treated in CHERISH and 31 initiated treatment in SHINE.

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Investigators found that all but 3 items on RULM improved on average from baseline until day 930. The highest mean increases were seen in tearing paper (+0.5), lifting a 500-gram weight horizontally (+0.5), tracing a path (+0.4), and pushing on light (+0.4). The highest percentage of participants gaining abilities was seen in tearing paper (46%), pushing on light (33%), and opening Ziploc container (25%). Participants lost abilities such as shoulder flexion (12%), shoulder abduction (11%), and reaching to side (6%). Gains in activities were observed across all age groups, although younger participants gained more activities than older participants. Notably, older participants gained activities relating to hand dexterity and manipulation.

CHERISH was a phase 3, double-blind, randomized, sham-controlled study that assessed 12 mg intrathecal nusinersen or sham in 126 participants. Primary outcomes assessed change in Hammersmith Functional Motor Scale – Expanded (HFMSE) scores, motor milestones, RULM, safety, abnormalities, and concomitant medications.

SHINE was a phase 3 open-label extension that enrolled 292 participants that previously participated in other studies of nusinersen, including CHERISH. Primary outcomes included safety via adverse events (AEs), abnormalities, and concomitant medications, while secondary outcomes included changes inmotor milestones, Hammersmith Infant Neurological Examination, death/permanent ventilation, Children’s Hospital of Philadelphia Infant test of Neuromuscular Disorders scale, HFMSE, RULM, 6-minute walk test, Compound Muscular Action Potential, sizes of body parts, hospitalizations, respiratory events, quality of life, survival, and other measures.

“Gain of activities that are associated with meaningful activities of daily living were observed in CHERISH/SHINE participants across all age groups. The oldest group in CHERISH/SHINE continued to gain in some acitivties, including those related to hand dexterity and manipulation,” Montes and colleagues concluded.

Read more coverage of the 2023 MDA Conference here.

Montes J, Youn B, Pasternak A, et al. Longitudinal Changes in Items of the Revised Upper Limb Module in Later-Onset SMA: Results from CHERISH/SHINE. Presented at: 2023 MDA Conference, March 19-22; Dallas, Texas. Poster #156
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