Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5‐year update of the NURTURE study

Introduction/Aims NURTURE (NCT02386553) is an open‐label study of nusinersen in children (two SMN2 copies, n = 15; three SMN2 copies, n = 10) who initiated treatment in the presymptomatic stage of spinal muscular atrophy (SMA). A prior analysis after ~3 y showed benefits on survival, respiratory out...

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Published in:Muscle & nerve 2023-08, Vol.68 (2), p.157-170
Main Authors: Crawford, Thomas O., Swoboda, Kathryn J., De Vivo, Darryl C., Bertini, Enrico, Hwu, Wuh‐Liang, Finkel, Richard S., Kirschner, Janbernd, Kuntz, Nancy L., Nazario, Aledie Navas, Parsons, Julie A., Pechmann, Astrid, Ryan, Monique M., Butterfield, Russell J., Topaloglu, Haluk, Ben‐Omran, Tawfeg, Sansone, Valeria A., Jong, Yuh‐Jyh, Shu, Francy, Zhu, Cong, Raynaud, Stephanie, Lago, Tiffany R., Paradis, Angela D., Foster, Richard, Chin, Russell, Berger, Zdenek
Format: Article
Language:English
Subjects:
Action potential
Atrophy
Children
Durability
motor function
Neuromuscular diseases
NURTURE
nusinersen
Ostomy
Safety
SMN protein
Spinal muscular atrophy
Subgroups
Survival
Tracheostomy
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Summary:Introduction/Aims NURTURE (NCT02386553) is an open‐label study of nusinersen in children (two SMN2 copies, n = 15; three SMN2 copies, n = 10) who initiated treatment in the presymptomatic stage of spinal muscular atrophy (SMA). A prior analysis after ~3 y showed benefits on survival, respiratory outcomes, motor milestone achievement, and a favorable safety profile. An additional 2 y of follow‐up (data cut: February 15, 2021) are reported. Methods The primary endpoint is time to death or respiratory intervention (≥6 h/day continuously for ≥7 days or tracheostomy). Secondary outcomes include overall survival, motor function, and safety. Results Median age of children was 4.9 (3.8–5.5) y at last visit. No children have discontinued the study or treatment. All were alive. No additional children utilized respiratory intervention (defined per primary endpoint) since the prior data cut. Children with three SMN2 copies achieved all World Health Organization (WHO) motor milestones, with all but one milestone in one child within normal developmental timeframes. All 15 children with two SMN2 copies achieved sitting without support, 14/15 walking with assistance, and 13/15 walking alone. Mean Hammersmith Functional Motor Scale Expanded total scores showed continued improvement. Subgroups with two SMN2 copies, minimum baseline compound muscle action potential amplitude ≥2 mV, and no baseline areflexia had better motor and nonmotor outcomes versus all children with two SMN2 copies. Discussion These results demonstrate the value of early treatment, durability of treatment effect, and favorable safety profile after ~5 y of nusinersen treatment. Inclusion/exclusion criteria and baseline characteristics should be considered when interpreting presymptomatic SMA trial data. Results from the ongoing NURTURE study demonstrate durability of effect and favorable safety profile of nusinersen in 25 children with two or three SMN2 copies who initiated treatment in the presymptomatic stage of spinal muscular atrophy (SMA). After ~5 y, all children achieved previously unattainable motor milestones, many within normal developmental timeframes, emphasizing the value of early diagnosis and early initiation of nusinersen. Subgroup analyses suggest inclusion/exclusion criteria and baseline characteristics should be considered when interpreting presymptomatic SMA trial data.
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.27853