Abstract Details

Title The RESTORE Registry: Comparative Outcomes in Patients with Spinal Muscular Atrophy (SMA) in the United States Identified by Newborn Screening (NBS) or Clinical Diagnosis

Topic Child Neurology and Developmental Neurology

Presentation(s) P15 - Poster Session 15 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-003

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.

Objective We sought to better understand outcomes in US children with SMA identified by NBS/prenatal screening versus those diagnosed clinically.

Design/Methods

We stratified patients in RESTORE (a prospective, multicenter, multinational, 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. All other patients 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 patients 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.

Authors/Disclosures
PRESENTER	No disclosure on file
Darryl C. De Vivo, MD, FAAN (Columbia University)	Dr. De Vivo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen and Novartis. Dr. De Vivo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aspa Therapeutics.
Janbernd Kirschner	No disclosure on file
	No disclosure on file
Francesco Muntoni, MD (UCL Institute of Child Health)	Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sarepta. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizer. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Avexis. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Dr. Muntoni has received research support from European Commission. The institution of Dr. Muntoni has received research support from Medical Research Council. The institution of Dr. Muntoni has received research support from Biogen. The institution of Dr. Muntoni has received research support from Muscular Dystrophy UK. The institution of Dr. Muntoni has received research support from MDA USA. The institution of Dr. Muntoni has received research support from Sarepta. The institution of Dr. Muntoni has received research support from Association Francoise Myopathies. Dr. Muntoni has received personal compensation in the range of $0-$499 for serving as a Clinical expert with UK NICE Committee.
	No disclosure on file
Susana Quijano-Roy (Aphp Paris Saclay, Hôpital Raymond Poincaré)	No disclosure on file
Kayoko Saito	No disclosure on file
	No disclosure on file
	No disclosure on file
Fred Anderson, PhD	Dr. Anderson has nothing to disclose.
Omar Dabbous	Omar Dabbous has received personal compensation for serving as an employee of Novartis Gene Therapies. Omar Dabbous has received stock or an ownership interest from Novartis Gene Therapies.
Richard S. Finkel, MD, FAAN (St. Jude Children's Research Hospital)	Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Finkel has received research support from AveXis. The institution of Dr. Finkel has received research support from Biogen. The institution of Dr. Finkel has received research support from Capricor. The institution of Dr. Finkel has received research support from Catabasis. The institution of Dr. Finkel has received research support from ReveraGen. The institution of Dr. Finkel has received research support from Roche. The institution of Dr. Finkel has received research support from Scholar Rock. Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. Dr. Finkel has received personal compensation in the range of $0-$499 for serving as a Speaker in workshop with National Academy of Sciences. Dr. Finkel has a non-compensated relationship as a advisor with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Finkel has a non-compensated relationship as a Board Member with EveryLife Foundation that is relevant to AAN interests or activities.