The Lancet Regional Health. Europe (Dec 2024)
Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational studyResearch in context
- Claudia Weiß,
- Lena-Luise Becker,
- Johannes Friese,
- Astrid Blaschek,
- Andreas Hahn,
- Sabine Illsinger,
- Oliver Schwartz,
- Günther Bernert,
- Maja von der Hagen,
- Ralf A. Husain,
- Klaus Goldhahn,
- Janbernd Kirschner,
- Astrid Pechmann,
- Marina Flotats-Bastardas,
- Gudrun Schreiber,
- Ulrike Schara,
- Barbara Plecko,
- Regina Trollmann,
- Veronka Horber,
- Ekkehard Wilichowski,
- Matthias Baumann,
- Andrea Klein,
- Astrid Eisenkölbl,
- Cornelia Köhler,
- Georg M. Stettner,
- Sebahattin Cirak,
- Oswald Hasselmann,
- Angela M. Kaindl,
- Sven F. Garbade,
- Jessika Johannsen,
- Andreas Ziegler,
- Petra Baum,
- Manuela Baumgartner,
- Astrid Bertsche,
- Markus Blankenburg,
- Jonas Denecke,
- Marcus Deschauer,
- Matthias Eckenweiler,
- Tobias Geis,
- Klaus Goldhahn,
- Martin Groß,
- René Günther,
- Tim Hagenacker,
- Eckard Hamelmann,
- Ralf A. Husain,
- Christoph Kamm,
- Birgit Kauffmann,
- Jan Christoph Koch,
- Wolfgang Löscher,
- Albert Ludolph,
- Pascal Martin,
- Alexander Mensch,
- Gerd Meyer zu Hörste,
- Christoph Neuwirth,
- Susanne Petri,
- Manuel Pühringer,
- Imke Rathmann,
- Dorothee Schäfer,
- Mareike Schimmel,
- Bertold Schrank,
- Olivia Schreiber-Katz,
- Anette Schwerin-Nagel,
- Martin Smitka,
- Meike Steinbach,
- Elisabeth Steiner,
- Johannes Stoffels,
- Manuela Theophil,
- Raffi Topakian,
- Matthias Türk,
- Matthias Vorgerd,
- Maggie C. Walter,
- Markus Weiler,
- Gert Wiegand,
- Gilbert Wunderlich,
- Claudia Diana Wurster,
- Daniel Zeller,
- Moritz Metelmann,
- Fiona Zeiner,
- Veronika Pilshofer,
- Mika Rappold,
- Josefine Pauschek,
- Christof Reihle,
- Annette Karolin Homma,
- Paul Lingor,
- Bettina Henzi,
- Elisabeth Steiner,
- Tabea Reinhardt,
- Dorothea Holzwarth,
- Wolfgang Wittmann,
- Manuela Theophil,
- Stefan Kappel,
- Maren Freigang,
- Benjamin Stolte,
- Kyriakos Martakis,
- Georg Classen,
- Doris Roland-Schäfer,
- Daniela Steuernagel,
- Hans Hartmann,
- Sophie Fischer,
- Marieke Wermuth,
- Mohamad Tareq Muhandes,
- Anna Hotter,
- Zeljko Uzelac,
- Steffen Naegel,
- Sarah Wiethoff,
- Nathalie Braun,
- Bogdan Bjelica,
- Heike Kölbel,
- Daniela Angelova-Toshkina,
- Bernd Wilken,
- Alma Osmanovic,
- Barbara Fiedler,
- Barbara Plecko,
- Maike Tomforde,
- Thomas Voelkl,
- Arpad von Moers,
- Petra Müller,
- Bettina Behring,
- Anne Güttsches,
- Peter Reilich,
- Wolfgang Wick,
- Corinna Stoltenburg,
- Simon Witzel,
- Julia Bellut,
- Georg Friedrich Hoffmann,
- Wolfgang Löscher,
- Kathrin Mörtlbauer,
- Alexandra Ille,
- Michael Schroth,
- Joenna Driemeyer,
- Luisa Semmler,
- Cornelia Müller,
- Katharina Dörnbrack,
- Manuel Pühringer,
- Michael Zemlin,
- Stephanie Geitmann,
- Hanna Sophie Lapp,
- Svenja Brakemeier,
- Tascha Gehrke,
- Klearchos Ntemiris,
- Nadja Kaiser,
- Sabine Borowski,
- Barbara Ramadan,
- Ulf Hustedt,
- Tobias Baum,
- Simon Witzel,
- Ilka Schneider,
- Esra Akova-Oztürk,
- Katharina Vill,
- Zylfie Dibrani,
- Camilla Wohnrade,
- Adela Della-Marina,
- Lisa Jung,
- Timo Deba,
- Joachim Zobel,
- Jens Schallner,
- Christina Kraut,
- Klaus Goldhahn,
- Peter Vollmann,
- Stephanie Schüssler,
- Melanie Roeder,
- Miriam Hiebeler,
- Nicole Berberich,
- Joanna Schneider,
- Zeljko Uzelac,
- Brigitte Brauner,
- Stefan Kölker,
- Elke Pernegger,
- Magdalena Gosk-Tomek,
- Sarah Braun,
- Deike Weiss,
- Gerrit Machetanz,
- Thorsten Langer,
- Christina Saier,
- Sandra Baumann,
- Sabine Hettrich,
- Gabriel Dworschak,
- Katharina Müller-Kaempffer,
- Isabelle Dittes,
- Andreas Thimm,
- Lisa Quinten,
- Kristina Albers,
- Andrea Bevot,
- Christa Bretschneider,
- Johannes Dorst,
- Thomas Kendzierski,
- Iris Hannibal,
- Jasmin Bischofberger,
- Tilman Riesmeier,
- Andrea Gangfuß,
- Eva Johann to Settel,
- Michael Grässl,
- Susan Fiebig,
- Carmen Hollerauer,
- Lea Seeber,
- Ina Krahwinkler,
- Irene Lange,
- Federica Montagnese,
- Marcel Mann-Richter,
- Alexandra Wagner,
- Johannes Dorst,
- Christine Leypold,
- Afshin Saffari,
- Elmecker Anna,
- Anna Wiesenhofer,
- Eva-Maria Wendel,
- Paula-Sophie Steffens,
- Sabine Wider,
- Adrian Tassoni,
- Andrea Dall,
- Franziska Busch,
- Daniela Zeisler,
- Maria Wessel,
- Jaqueline Lipka,
- Andrea Hackemer,
- Loreen Plugge,
- Eva Jansen,
- Erdmute Roth,
- Joachim Schuster,
- Anna Koelsch,
- Birgit Warken-Madelung,
- Michaela Schwippert,
- Britta Holtkamp,
- Katja Köbbing,
- Sander Claeys,
- Sandy Foerster,
- Daniela Zeisler,
- Simone Thiele,
- Heidi Rochau-Trumpp,
- Annette George,
- Joachim Schuster,
- Moritz Niesert,
- Tanja Neimair,
- Katia Vettori,
- Julia Haverkamp,
- Jila Taherpour,
- Juliane Hug,
- Franziska Wenzel,
- Christina Bant,
- Ute Baur,
- Kathrin Bühner,
- Melina Schlag,
- Lena Ruß,
- Hanna Küpper,
- Anja Müller,
- Kurt Wollinsky,
- Therese Well,
- Antonia Leinert,
- Barbara Andres,
- Heymut Omran,
- Nicole Claus,
- Kathrin Bühner,
- Anna Hagenmeyer,
- Marion Schnurr,
- Vladimir Dukic,
- Albert Christian Ludolph,
- Sabine Specht,
- Verena Angermair,
- Anna Hüpper,
- Daniela Banholzer,
- Sabine Stein,
- Tim Kampowski,
- Marion Richmann,
- Sylke Nicolai,
- Omar Atta,
- Birgit Meßmer,
- Heike de Vries,
- Elisabeth Rotenfusser,
- Alma Oscmanovic,
- Isabelle Renger,
- Hélène Guillemot,
- Ilka Lehnert,
- Mike Grünwedel,
- Laura Grimm,
- Guido Stocker,
- Angela M. Kaindl,
- Kurt Wollinsky,
- Annegret Hoevel,
- Theresa Stadler,
- Michal Fischer,
- Sibylle Vogt,
- Axel Gebert,
- Maggie C. Walter,
- Susanne Goldbach,
- Tim Hagenacker,
- Janbernd Kirschner,
- Hanns Lochmüller,
- Wolfgang Müller-Felber,
- Astrid Pechmann,
- Ulrike Schara-Schmidt,
- Kristina Probst-Schendzielorz,
- Annina Lang,
- Maren Nitzsche,
- Olivia Schreiber-Katz,
- Julie Hammer,
- Katharina Müller-Kaempfer,
- Corinna Wirner-Piotrowski,
- Lieske van der Stam,
- Anke Bongartz,
- Susanne Goldbach,
- Hanns Lochmüller,
- Cornelia Enzmann,
- Joël Fluss,
- Elea Galiart,
- Bettina Henzi,
- David Jacquier,
- Dominique Baumann Metzler,
- Anne Tscherter,
- Kristina Probst-Schendzielorz
Affiliations
- Claudia Weiß
- Charité–Universitätsmedizin Berlin, Department of Pediatric Neurology, Augustenburger Platz 1, Berlin 13353, Germany; Charité–Universitätsmedizin Berlin, Center for Chronically Sick Children, Augustenburger Platz 1, Berlin 13353, Germany; Department of Child Neurology, University Hospital Bonn, Venusberg-Campus 1, Bonn 53127, Germany
- Lena-Luise Becker
- Charité–Universitätsmedizin Berlin, Department of Pediatric Neurology, Augustenburger Platz 1, Berlin 13353, Germany; Charité–Universitätsmedizin Berlin, Center for Chronically Sick Children, Augustenburger Platz 1, Berlin 13353, Germany; Charité–Universitätsmedizin Berlin, Institute of Cell Biology and Neurobiology, Augustenburger Platz 1, Berlin 13353, Germany; Department of Child Neurology, University Hospital Bonn, Venusberg-Campus 1, Bonn 53127, Germany; Department of Pediatric Neurology and Developmental Medicine, Ludwig Maximilian University of Munich (LMU), Hauner Children’s Hospital, Lindwurmstr. 4, Munich 80337, Germany
- Johannes Friese
- Charité–Universitätsmedizin Berlin, Center for Chronically Sick Children, Augustenburger Platz 1, Berlin 13353, Germany; Department of Child Neurology, University Hospital Bonn, Venusberg-Campus 1, Bonn 53127, Germany
- Astrid Blaschek
- Charité–Universitätsmedizin Berlin, Institute of Cell Biology and Neurobiology, Augustenburger Platz 1, Berlin 13353, Germany; Department of Pediatric Neurology and Developmental Medicine, Ludwig Maximilian University of Munich (LMU), Hauner Children’s Hospital, Lindwurmstr. 4, Munich 80337, Germany
- Andreas Hahn
- Department of Child Neurology, University Hospital, Rudolf-Buchheim-Str. 8, Gießen 35392, Germany
- Sabine Illsinger
- Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany
- Oliver Schwartz
- Department of Pediatric Neurology, University Hospital, Albert-Schweitzer-Strasse 33, Münster, Germany
- Günther Bernert
- Department of Pediatrics, Klinik Favoriten, Kundratstr. 3, Vienna 1100, Austria
- Maja von der Hagen
- Department of Neuropediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Dresden 01307, Germany
- Ralf A. Husain
- Department of Neuropediatrics, Jena University Hospital, Bachstr. 18, Jena 07743, Germany
- Klaus Goldhahn
- Department of Pediatrics and Neuropediatrics, DRK Klinikum Westend, Spandauer Damm 130, Berlin 14050, Germany
- Janbernd Kirschner
- Department of Neuropediatrics and Muscle Disorders, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Heiliggeist-Str. 1, Freiburg 79106, Germany
- Astrid Pechmann
- Department of Neuropediatrics and Muscle Disorders, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Heiliggeist-Str. 1, Freiburg 79106, Germany
- Marina Flotats-Bastardas
- University Hospital Homburg, Department of Pediatric Neurology, Kirrberger Str. 100, Homburg 66421, Germany
- Gudrun Schreiber
- Klinikum Kassel, Department of Pediatric Neurology, Mönchebergstr. 41-43, Kassel 34125, Germany
- Ulrike Schara
- Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Center for Translational Neuro and Behavioral Sciences, University Duisburg-Essen, Germany
- Barbara Plecko
- Department of Pediatrics and Adolescent Medicine, Division of General Pediatrics, Medical University Graz, Auenbruggerplatz 2, Graz 8036, Austria
- Regina Trollmann
- Department of Pediatrics, Division of Pediatric Neurology, Friedrich-Alexander University of Erlangen-Nürnberg, Maximiliansplatz 2, Erlangen 91054, Germany
- Veronka Horber
- Department of Pediatric Neurology, University Children’s Hospital, Hoppe-Seyler-Str. 1, Tübingen 72076, Germany
- Ekkehard Wilichowski
- Department of Paediatrics and Adolescent Medicine, Division of Paediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany
- Matthias Baumann
- Department of Pediatrics I, Division of Pediatric Neurology, Medical University Innsbruck, Innsbruck, Austria
- Andrea Klein
- Division of Neuropediatrics, Development and Rehabilitation, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Astrid Eisenkölbl
- Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Kepler University Hospital, Krankenhausstrasse 26-30, Linz 4020, Austria
- Cornelia Köhler
- Bochum Department of Neuropediatrics, University Children’s Hospital, Ruhr-University Bochum, Bochum, Germany
- Georg M. Stettner
- Neuromuscular Center Zurich and Department of Pediatric Neurology, University Children’s Hospital Zurich, University of Zurich, Steinwiesstrasse 75, Zurich CH-8032, Switzerland
- Sebahattin Cirak
- Ulm University, Department of Pediatrics, Albert-Einstein-Allee 23, Ulm 89081, Germany
- Oswald Hasselmann
- Department of Neuropediatrics, Children’s Hospital of Eastern Switzerland, St. Gallen, Switzerland
- Angela M. Kaindl
- Charité–Universitätsmedizin Berlin, Department of Pediatric Neurology, Augustenburger Platz 1, Berlin 13353, Germany; Charité–Universitätsmedizin Berlin, Center for Chronically Sick Children, Augustenburger Platz 1, Berlin 13353, Germany; Charité–Universitätsmedizin Berlin, Institute of Cell Biology and Neurobiology, Augustenburger Platz 1, Berlin 13353, Germany; Department of Child Neurology, University Hospital Bonn, Venusberg-Campus 1, Bonn 53127, Germany; Department of Pediatric Neurology and Developmental Medicine, Ludwig Maximilian University of Munich (LMU), Hauner Children’s Hospital, Lindwurmstr. 4, Munich 80337, Germany
- Sven F. Garbade
- Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, Im Neuenheimer Feld 430, Heidelberg 69120, Germany
- Jessika Johannsen
- University Medical Center Hamburg-Eppendorf, Department of Pediatrics, Martinistr. 52, Hamburg 20246, Germany
- Andreas Ziegler
- Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, Im Neuenheimer Feld 430, Heidelberg 69120, Germany; Corresponding author. Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, Im Neuenheimer Feld 430, Heidelberg 69120, Germany.
- Petra Baum
- Manuela Baumgartner
- Astrid Bertsche
- Markus Blankenburg
- Jonas Denecke
- Marcus Deschauer
- Matthias Eckenweiler
- Tobias Geis
- Klaus Goldhahn
- Martin Groß
- René Günther
- Tim Hagenacker
- Eckard Hamelmann
- Ralf A. Husain
- Christoph Kamm
- Birgit Kauffmann
- Jan Christoph Koch
- Wolfgang Löscher
- Albert Ludolph
- Pascal Martin
- Alexander Mensch
- Gerd Meyer zu Hörste
- Christoph Neuwirth
- Susanne Petri
- Manuel Pühringer
- Imke Rathmann
- Dorothee Schäfer
- Mareike Schimmel
- Bertold Schrank
- Olivia Schreiber-Katz
- Anette Schwerin-Nagel
- Martin Smitka
- Meike Steinbach
- Elisabeth Steiner
- Johannes Stoffels
- Manuela Theophil
- Raffi Topakian
- Matthias Türk
- Matthias Vorgerd
- Maggie C. Walter
- Markus Weiler
- Gert Wiegand
- Gilbert Wunderlich
- Claudia Diana Wurster
- Daniel Zeller
- Moritz Metelmann
- Fiona Zeiner
- Veronika Pilshofer
- Mika Rappold
- Josefine Pauschek
- Christof Reihle
- Annette Karolin Homma
- Paul Lingor
- Bettina Henzi
- Elisabeth Steiner
- Tabea Reinhardt
- Dorothea Holzwarth
- Wolfgang Wittmann
- Manuela Theophil
- Stefan Kappel
- Maren Freigang
- Benjamin Stolte
- Kyriakos Martakis
- Georg Classen
- Doris Roland-Schäfer
- Daniela Steuernagel
- Hans Hartmann
- Sophie Fischer
- Marieke Wermuth
- Mohamad Tareq Muhandes
- Anna Hotter
- Zeljko Uzelac
- Steffen Naegel
- Sarah Wiethoff
- Nathalie Braun
- Bogdan Bjelica
- Heike Kölbel
- Daniela Angelova-Toshkina
- Bernd Wilken
- Alma Osmanovic
- Barbara Fiedler
- Barbara Plecko
- Maike Tomforde
- Thomas Voelkl
- Arpad von Moers
- Petra Müller
- Bettina Behring
- Anne Güttsches
- Peter Reilich
- Wolfgang Wick
- Corinna Stoltenburg
- Simon Witzel
- Julia Bellut
- Georg Friedrich Hoffmann
- Wolfgang Löscher
- Kathrin Mörtlbauer
- Alexandra Ille
- Michael Schroth
- Joenna Driemeyer
- Luisa Semmler
- Cornelia Müller
- Katharina Dörnbrack
- Manuel Pühringer
- Michael Zemlin
- Stephanie Geitmann
- Hanna Sophie Lapp
- Svenja Brakemeier
- Tascha Gehrke
- Klearchos Ntemiris
- Nadja Kaiser
- Sabine Borowski
- Barbara Ramadan
- Ulf Hustedt
- Tobias Baum
- Simon Witzel
- Ilka Schneider
- Esra Akova-Oztürk
- Katharina Vill
- Zylfie Dibrani
- Camilla Wohnrade
- Adela Della-Marina
- Lisa Jung
- Timo Deba
- Joachim Zobel
- Jens Schallner
- Christina Kraut
- Klaus Goldhahn
- Peter Vollmann
- Stephanie Schüssler
- Melanie Roeder
- Miriam Hiebeler
- Nicole Berberich
- Joanna Schneider
- Zeljko Uzelac
- Brigitte Brauner
- Stefan Kölker
- Elke Pernegger
- Magdalena Gosk-Tomek
- Sarah Braun
- Deike Weiss
- Gerrit Machetanz
- Thorsten Langer
- Christina Saier
- Sandra Baumann
- Sabine Hettrich
- Gabriel Dworschak
- Katharina Müller-Kaempffer
- Isabelle Dittes
- Andreas Thimm
- Lisa Quinten
- Kristina Albers
- Andrea Bevot
- Christa Bretschneider
- Johannes Dorst
- Thomas Kendzierski
- Iris Hannibal
- Jasmin Bischofberger
- Tilman Riesmeier
- Andrea Gangfuß
- Eva Johann to Settel
- Michael Grässl
- Susan Fiebig
- Carmen Hollerauer
- Lea Seeber
- Ina Krahwinkler
- Irene Lange
- Federica Montagnese
- Marcel Mann-Richter
- Alexandra Wagner
- Johannes Dorst
- Christine Leypold
- Afshin Saffari
- Elmecker Anna
- Anna Wiesenhofer
- Eva-Maria Wendel
- Paula-Sophie Steffens
- Sabine Wider
- Adrian Tassoni
- Andrea Dall
- Franziska Busch
- Daniela Zeisler
- Maria Wessel
- Jaqueline Lipka
- Andrea Hackemer
- Loreen Plugge
- Eva Jansen
- Erdmute Roth
- Joachim Schuster
- Anna Koelsch
- Birgit Warken-Madelung
- Michaela Schwippert
- Britta Holtkamp
- Katja Köbbing
- Sander Claeys
- Sandy Foerster
- Daniela Zeisler
- Simone Thiele
- Heidi Rochau-Trumpp
- Annette George
- Joachim Schuster
- Moritz Niesert
- Tanja Neimair
- Katia Vettori
- Julia Haverkamp
- Jila Taherpour
- Juliane Hug
- Franziska Wenzel
- Christina Bant
- Ute Baur
- Kathrin Bühner
- Melina Schlag
- Lena Ruß
- Hanna Küpper
- Anja Müller
- Kurt Wollinsky
- Therese Well
- Antonia Leinert
- Barbara Andres
- Heymut Omran
- Nicole Claus
- Kathrin Bühner
- Anna Hagenmeyer
- Marion Schnurr
- Vladimir Dukic
- Albert Christian Ludolph
- Sabine Specht
- Verena Angermair
- Anna Hüpper
- Daniela Banholzer
- Sabine Stein
- Tim Kampowski
- Marion Richmann
- Sylke Nicolai
- Omar Atta
- Birgit Meßmer
- Heike de Vries
- Elisabeth Rotenfusser
- Alma Oscmanovic
- Isabelle Renger
- Hélène Guillemot
- Ilka Lehnert
- Mike Grünwedel
- Laura Grimm
- Guido Stocker
- Angela M. Kaindl
- Kurt Wollinsky
- Annegret Hoevel
- Theresa Stadler
- Michal Fischer
- Sibylle Vogt
- Axel Gebert
- Maggie C. Walter
- Susanne Goldbach
- Tim Hagenacker
- Janbernd Kirschner
- Hanns Lochmüller
- Wolfgang Müller-Felber
- Astrid Pechmann
- Ulrike Schara-Schmidt
- Kristina Probst-Schendzielorz
- Annina Lang
- Maren Nitzsche
- Olivia Schreiber-Katz
- Julie Hammer
- Katharina Müller-Kaempfer
- Corinna Wirner-Piotrowski
- Lieske van der Stam
- Anke Bongartz
- Susanne Goldbach
- Hanns Lochmüller
- Cornelia Enzmann
- Joël Fluss
- Elea Galiart
- Bettina Henzi
- David Jacquier
- Dominique Baumann Metzler
- Anne Tscherter
- Kristina Probst-Schendzielorz
- Journal volume & issue
-
Vol. 47
p. 101092
Abstract
Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).