Outcomes in US Spinal Muscular Atrophy (SMA) Patients Identified by Newborn Screening (NBS) or Clinical Diagnosis: Findings from the RESTORE Registry


Clinical Management

Poster Number: 78


Laurent Servais, MD, PhD, Department of Pediatrics, MDUK Oxford Neuromuscular Center, University of Oxford, Darryl De Vivo, MD, Columbia University Medical Center, Janbernd Kirschner, MD, Medical Center-University of Freiburg; University Hospital Bonn, Faculty of Medicine, Eugenio Mercuri, Paediatric Neurology and Centro Clinico Nemo, Catholic University and Policlinico Gemelli, Fondazion, Francesco Muntoni, MD, Great Ormond Street Institute of Child Health, London, UK, Eduardo Tizzano, Department of Clinical and Molecular Genetics, Hospital Valle Hebron, Susana Quijano-Roy, Garches Neuromuscular Reference Center, APHP Raymond Poincare University Hospital, Kayoko Saito, MD, PhD, Institute of Medical Genetics, Tokyo Women’s Medical University, Melissa Menier, Atlas Clarity LLC, Nicole LaMarca, DNP, MSN, CPNP, PMHS, Novartis Gene Therapies, Frederick A. Anderson, Center for Outcomes Research, University of Massachusetts Medical School, Omar Dabbous, Novartis Gene Therapies, Richard Finkel, MD, St. Jude Children’s Research Hospital, Memphis, TN, USA.

Objective: We sought to better understand outcomes in US children with SMA identified by NBS/prenatal screening versus those diagnosed clinically.
Background: In SMA type 1, timely intervention is critical for preservation of motor function and survival. Early detection through NBS enables more rapid diagnosis and intervention.
Methods: We stratified patients in RESTORE, a prospective, multi-center, multi-national, observational SMA patient registry, with ?2 SMN2 gene copies and ?16 months of follow-up into two groups based on SMA identification: clinical diagnosis based on SMA symptoms or NBS/prenatal screening. We compared age at diagnosis, age at first treatment, time from diagnosis to first treatment, percentage receiving monotherapy versus >1 treatment, and motor function changes.
Results: As of May 23, 2021, 55 patients met analysis criteria (42 clinically diagnosed; 13 NBS/prenatal diagnosis). Two NBS patients had one copy of the SMN2 gene, while all others had two SMN2 copies. For clinically diagnosed patients compared with NBS patients, mean age at diagnosis was 3.2 versus 0.8 months (p<0.0001); age at first treatment was 4.9 versus 1.7 months (p<0.0001); and time from diagnosis to initial treatment was 1.3 versus 1.2 months (p=0.8099 [nonsignificant]). A significantly greater percentage of clinically diagnosed patients received >1 SMA therapy compared with NBS patients (90.5% [n=38/42] vs. 53.9% [n=7/13], respectively; p=0.0118). CHOP INTEND increases of ?4 points were observed for 75.0% (n=15/20) of clinically diagnosed patients and 83.3% (n=5/6) of individuals identified by NBS. Patients identified via NBS consistently achieved motor milestones at younger ages compared with clinically diagnosed patients.
Conclusions: NBS for SMA is associated with significantly earlier diagnosis and intervention. Compared with those who were clinically diagnosed, patients identified by NBS consistently achieved motor milestones at earlier ages, and more consistently achieved ?4-point CHOP INTEND increases. A significantly greater percentage of clinically diagnosed patients received >1 SMA therapy.