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Controlled Clinical Trial
. 2024 Jun 1;178(6):540-547.
doi: 10.1001/jamapediatrics.2024.0492.

Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial

Oliver Schwartz  1 , Katharina Vill  2   3 , Michelle Pfaffenlehner  4   5 , Max Behrens  4   5 , Claudia Weiß  6 , Jessika Johannsen  7 , Johannes Friese  8 , Andreas Hahn  9 , Andreas Ziegler  10 , Sabine Illsinger  11 , Martin Smitka  12 , Arpad von Moers  13 , Heike Kölbel  14 , Gudrun Schreiber  15 , Nadja Kaiser  16 , Ekkehard Wilichowski  17 , Marina Flotats-Bastardas  18 , Ralf A Husain  19 , Matthias Baumann  20 , Cornelia Köhler  21 , Regina Trollmann  22 , Annette Schwerin-Nagel  23 , Astrid Eisenkölbl  24 , Mareike Schimmel  25 , Martin Fleger  26 , Birgit Kauffmann  27 , Gert Wiegand  28 , Manuela Baumgartner  29 , Christian Rauscher  30 , Sebahattin Cirak  31 , Dieter Gläser  32 , Günther Bernert  33 , Tim Hagenacker  34 , Susanne Goldbach  35 , Kristina Probst-Schendzielorz  35 , Hanns Lochmüller  36   37 , Wolfgang Müller-Felber  2 , Ulrike Schara-Schmidt  14 , Maggie C Walter  38 , Janbernd Kirschner  37 , Astrid Pechmann  37 ; SMARTCARE study group
Collaborators, Affiliations
Controlled Clinical Trial

Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial

Oliver Schwartz et al. JAMA Pediatr. .

Abstract

Importance: There is increasing evidence that early diagnosis and treatment are key for outcomes in infants with spinal muscular atrophy (SMA), and newborn screening programs have been implemented to detect the disease before onset of symptoms. However, data from controlled studies that reliably confirm the benefits of newborn screening are lacking.

Objective: To compare data obtained on patients with SMA diagnosed through newborn screening and those diagnosed after clinical symptom onset.

Design, setting, and participants: This nonrandomized controlled trial used data from the SMARTCARE registry to evaluate all children born between January 2018 and September 2021 with genetically confirmed SMA and up to 3 SMN2 copies. The registry includes data from 70 participating centers in Germany, Austria, and Switzerland. Data analysis was performed in February 2023 so that all patients had a minimal follow-up of 18 months.

Exposure: Patients born in 2 federal states in Germany underwent screening in a newborn screening pilot project. All other patients were diagnosed after clinical symptom onset. All patients received standard care within the same health care system.

Main outcomes: The primary end point was the achievement of motor milestones.

Results: A total of 234 children (123 [52.6%] female) were identified who met inclusion criteria and were included in the analysis: 44 (18.8%) in the newborn screening cohort and 190 children (81.2%) in the clinical symptom onset cohort. The mean (SD) age at start of treatment with 1 of the approved disease-modifying drugs was 1.3 (2.2) months in the newborn screening cohort and 10.7 (9.1) months in the clinical symptom onset cohort. In the newborn screening cohort, 40 of 44 children (90.9%) gained the ability to sit independently vs 141 of 190 (74.2%) in the clinical symptom onset cohort. For independent ambulation, the ratio was 28 of 40 (63.6%) vs 28 of 190 (14.7%).

Conclusions and relevance: This nonrandomized controlled trial demonstrated effectiveness of newborn screening for infants with SMA in the real-world setting. Functional outcomes and thus the response to treatment were significantly better in the newborn screening cohort compared to the unscreened clinical symptom onset group.

Trial registration: German Clinical Trials Register: DRKS00012699.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Schwartz reported speaker honoraria from Biogen outside the submitted work. Dr Vill reported personal fees from Santhera and ITF Pharma outside the submitted work. Dr Weiß reported personal fees from Novartis, Roche, and Biogen outside the submitted work. Dr Johannsen reported compensation for advisory boards and funding for travel or speaker honoraria from Avexis/Novartis, Biogen, Roche, PTC Therapeutics, Pfizer, Santhera, ITF Pharma, and Sarepta Therapeutics. Dr Ziegler reported grants and personal fees from Biogen and personal fees from Novartis and Roche outside the submitted work. Dr Illsinger reported personal fees for expert counseling from Novartis and Roche outside the submitted work. Dr Kölbel reported advisory and/or speaker fees from Biogen, Novartis, and Roche during the conduct of the study and speaker fees from Sanofi outside the submitted work. Dr Flotats-Bastardas reported personal fees from Roche, Novartis, and Biogen during the conduct of the study and outside the submitted work. Dr Husain reported personal fees from Biogen (advisory board), Roche (advisory board), and Novartis (conference session chair) during the conduct of the study. Dr Baumann reported consulting and lecture fees from Roche, Biogen, and Novartis outside the submitted work. Dr Schwerin-Nagel reported personal fees for serving on advisory boards for Novartis, Biogen, and Roche outside the submitted work. Dr Schimmel reported personal fees from Roche during the conduct of the study. Dr Wiegand reported compensation for advisory board service from Roche during the conduct of the study. Dr Hagenacker reported grants from Biogen, Novartis, and Roche and advisory board fees and lecture honoraria from Biogen and Roche outside the submitted work. Dr Müller-Felber reported personal fees from Novartis (gene therapy scientific talks, and advisory board), Roche (scientific talks), and Biogen (scientific talks) during the conduct of the study and personal fees from PTC Therapeutics (advisory board), Sarepta (scientific talks), Sanofi (scientific talks and advisory board), and Italfarmaco (scientific talks) outside the submitted work. Dr Schara-Schmidt reported personal fees for invited talks and advisory board service from Novartis, Biogen and Roche. Dr Walter reported personal fees from Biogen and personal fees from Roche outside the submitted work. Dr Kirschner reported grants from Biogen, Novartis, and Roche during the conduct of the study as well as grants from the European Union’s Innovative Medicines Initiative 2 Joint Undertaking (SCREEN4CARE) and the European Commission European Reference Network (EURO-NMD) and personal fees from ScholarRock, Biogen, Novartis, and Roche outside the submitted work. Dr Pechmann reported Novartis, Biogen, and Roche during the conduct of the study and grants from the European Union Innovative Medicines Initiative 2 Joint Undertaking (SCREEN4CARE) and the European Commission European Reference Network (EURO-NMD) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Flow Diagram
Figure 2.
Figure 2.. Probability of Gaining the Ability to Sit or Walk Independently
Shaded areas indicate 99% CIs. Solid vertical lines show the 50th percentile and dashed vertical lines the 99th percentile. CSO indicates those diagnosed after clinical symptom onset; NBS, those diagnosed via newborn screening.
Figure 3.
Figure 3.. Probability of Ventilator Support and Tube Feeding
Events are defined as new need for ventilator support or tube feeding independent of type of ventilator support or tube feeding. Shaded areas indicate 99% CIs. CSO indicates those diagnosed after clinical symptom onset; NBS, those diagnosed via newborn screening.
See this image and copyright information in PMC

Comment on

References

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