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

作者：Thomas O. Crawford, Kathryn J. Swoboda, Darryl C. De Vivo, Enrico Bertini, Wuh‐Liang Hwu, Richard S. Finkel, Janbernd Kirschner, Nancy L. Kuntz, Aledie Navas-Nazario, Julie A. Parsons, Astrid Pechmann, Monique M. Ryan, Russell J. Butterfield, Haluk Topaloğlu, Tawfeg Ben‐Omran, Valeria Sansone, Yuh‐Jyh Jong, Francy Shu, Cong Zhu, Stephanie Raynaud, Tiffany R. Lago, Angela D. Paradis, Richard Foster, Russell L. Chin, Zdenek Berger, the NURTURE Study Group · 发表于：Muscle & Nerve · 年份：2023 · DOI：10.1002/mus.27853 · 被引用次数：121 · 研究领域：Neurogenetic and Muscular Disorders Research、Amyotrophic Lateral Sclerosis Research、Craniofacial Disorders and Treatments

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. DISC...