Outcomes of Early-treated Infants with Spinal Muscular Atrophy: A Multicenter, Retrospective Cohort Study

Overview

Journal Muscle Nerve

Date 2024 Oct 7

PMID 39370660

Authors

Natalie L Goedeker

Amanda Rogers

Mark Fisher

Kapil Arya

John F Brandsema

Hiba Farah

Michelle A Farrar

Marcia V Felker

Melissa Gibbons

Omer Abdul Hamid

Matthew Harmelink

Karen Herbert

Elizabeth Kichula

Kiana King

Arpita Lakhotia

Bo Hoon Lee

Nancy L Kuntz

Julie Parsons

Rebecca Rehborg

Aravindhan Veerapaniyan

Craig M Zaidman

Affiliations

Soon will be listed here.

Abstract

Introduction/aims: While prompt identification and treatment of infants with spinal muscular atrophy (SMA) can ameliorate outcomes, variability persists. This study assessed management and outcomes of early-treated infants with SMA.

Methods: We analyzed retrospective data at 12 centers on infants with SMA treated at age ≤6 weeks from August 2018 to December 2023.

Results: Sixty-six patients, 35 with two SMN2 copies and 31 with ≥3 SMN2 copies, were included. Twenty-five (38%, 22 with two SMN2 copies), had SMA findings before initial treatment which was onasemnogene abeparvovec in 47 (71%) and nusinersen in 19 (29%). Thirty-two received sequential or combination treatments, including 16 adding nusinersen or risdiplam due to SMA findings following onasemnogene abeparvovec. All sat independently. Compared to children with ≥3 SMN2 copies, those with two SMN2 copies were less likely to walk (23/34 [68%] vs. 31/31 [100%], p < .001) and less likely to walk on time (9/34 [26%] vs. 29/31 [94%], p < .001); one non-ambulatory child was <18 months old and was excluded from this analysis. No patients required permanent ventilation or exclusively enteral nutrition; six required nocturnal non-invasive ventilation and four utilized supplemental enteral nutrition, all with two SMN2 copies.

Discussion: Early treatment of infants with SMA can improve outcomes as indicated by our cohort, all of whom sat independently and are without permanent ventilation. However, our study demonstrates ongoing disability in most children with two SMN2 copies despite early monotherapy and emphasizes the need for additional research, including earlier monotherapy, initial combination therapy, prenatal treatment, and non-SMN modifying treatments.

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