Orphanet Journal of Rare Diseases (Oct 2022)
Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study
- Astrid Pechmann,
- Max Behrens,
- Katharina Dörnbrack,
- Adrian Tassoni,
- Franziska Wenzel,
- Sabine Stein,
- Sibylle Vogt,
- Daniela Zöller,
- Günther Bernert,
- Tim Hagenacker,
- Ulrike Schara-Schmidt,
- Maggie C. Walter,
- Astrid Bertsche,
- Katharina Vill,
- Matthias Baumann,
- Manuela Baumgartner,
- Isabell Cordts,
- Astrid Eisenkölbl,
- Marina Flotats-Bastardas,
- Johannes Friese,
- René Günther,
- Andreas Hahn,
- Veronka Horber,
- Ralf A. Husain,
- Sabine Illsinger,
- Jörg Jahnel,
- Jessika Johannsen,
- Cornelia Köhler,
- Heike Kölbel,
- Monika Müller,
- Arpad von Moers,
- Annette Schwerin-Nagel,
- Christof Reihle,
- Kurt Schlachter,
- Gudrun Schreiber,
- Oliver Schwartz,
- Martin Smitka,
- Elisabeth Steiner,
- Regina Trollmann,
- Markus Weiler,
- Claudia Weiß,
- Gert Wiegand,
- Ekkehard Wilichowski,
- Andreas Ziegler,
- Hanns Lochmüller,
- Janbernd Kirschner,
- SMArtCARE study group
Affiliations
- Astrid Pechmann
- Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center – University of Freiburg, University of Freiburg
- Max Behrens
- Faculty of Medicine, Institute of Medical Biometry and Statistics, Medical Center – University of Freiburg
- Katharina Dörnbrack
- Clinical Trials Unit, Faculty of Medicine, Medical Center – University of Freiburg, University of Freiburg
- Adrian Tassoni
- Clinical Trials Unit, Faculty of Medicine, Medical Center – University of Freiburg, University of Freiburg
- Franziska Wenzel
- Clinical Trials Unit, Faculty of Medicine, Medical Center – University of Freiburg, University of Freiburg
- Sabine Stein
- Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center – University of Freiburg, University of Freiburg
- Sibylle Vogt
- Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center – University of Freiburg, University of Freiburg
- Daniela Zöller
- Faculty of Medicine, Institute of Medical Biometry and Statistics, Medical Center – University of Freiburg
- Günther Bernert
- Department of Pediatrics, Clinic Favoriten
- Tim Hagenacker
- Department of Neurology, Center for Translational Neuro‐ and Behavioral Sciences (C‐TNBS), University Medicine Essen
- Ulrike Schara-Schmidt
- Department of Neuropediatrics and Neuromuscular Centre for Children and Adolescents, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen
- Maggie C. Walter
- Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich
- Astrid Bertsche
- University Hospital for Children and Adolescents
- Katharina Vill
- Department of Pediatric Neurology and Developmental Medicine, LMU Center for Children With Medical Complexity, Dr. von Hauner Children’s Hospital, LMU Hospital, Ludwig-Maximilians-University
- Matthias Baumann
- Division of Pediatric Neurology, Department of Pediatrics I, Medical University of Innsbruck
- Manuela Baumgartner
- Department of Pediatrics and Adulescent Medicine, Ordensklinikum Linz, Barmherzige Schwestern
- Isabell Cordts
- Department of Neurology, Technical University of Munich, School of Medicine
- Astrid Eisenkölbl
- Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Kepler University Hospital
- Marina Flotats-Bastardas
- Department of Pediatric Neurology, Saarland University Hospital
- Johannes Friese
- Department of Neuropediatrics, University Hospital Bonn
- René Günther
- Department of Neurology, University Hospital Carl Gustav Carus
- Andreas Hahn
- Department of Child Neurology, Justus-Liebig University
- Veronka Horber
- Department of Paediatric Neurology, University Children’s Hospital
- Ralf A. Husain
- Department of Neuropediatrics, Jena University Hospital
- Sabine Illsinger
- Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical School
- Jörg Jahnel
- Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, LKH Klagenfurt, Medical University of Graz
- Jessika Johannsen
- Department of Pediatrics, University Medical Center Hamburg-Eppendorf
- Cornelia Köhler
- Abteilung Für Neuropädiatrie Und Sozialpädiatrie, Universitätsklinik Für Kinder- Und Jugendmedizin, St. Josef-Hospital, Ruhr-Universität Bochum
- Heike Kölbel
- Department of Neuropediatrics and Neuromuscular Centre for Children and Adolescents, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen
- Monika Müller
- Department of Neuropediatrics, University Children’s Hospital Würzburg
- Arpad von Moers
- Department of Pediatrics Und Neuropediatrics, DRK Kliniken Berlin
- Annette Schwerin-Nagel
- Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz
- Christof Reihle
- Department for Pediatric Neurology, Center for Child and Adolescent Medicine Olgahospital, Psychosomatic and Pain Medicine, Child Pain Center Baden-Württemberg, Klinikum Stuttgart
- Kurt Schlachter
- Department of Pediatrics, State Hospital of Bregenz
- Gudrun Schreiber
- Department of Pediatric Neurology, Klinikum Kassel
- Oliver Schwartz
- Department of Pediatric Neurology, Münster University Hospital
- Martin Smitka
- Abteilung Neuropaediatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden
- Elisabeth Steiner
- Department of Pediatrics and Adolescent Medicine, Johannes Kepler University/Hospital
- Regina Trollmann
- Division of Pediatric Neurology, Department of Pediatrics, Friedrich-Alexander-University of Erlangen-Nürnberg
- Markus Weiler
- Department of Neurology, Heidelberg University Hospital
- Claudia Weiß
- Department of Pediatric Neurology and Center for Chronically Sick Children, Charité – University Medicine Berlin
- Gert Wiegand
- Neuropediatrics Section of the Department of Pediatrics, Asklepios Clinic Hamburg Nord-Heidberg
- Ekkehard Wilichowski
- Department of Paediatrics and Pediatric Neurology, University Medical Centre, Georg August University Göttingen
- Andreas Ziegler
- Department of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg
- Hanns Lochmüller
- Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center – University of Freiburg, University of Freiburg
- Janbernd Kirschner
- Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center – University of Freiburg, University of Freiburg
- SMArtCARE study group
- DOI
- https://doi.org/10.1186/s13023-022-02547-8
- Journal volume & issue
-
Vol. 17,
no. 1
pp. 1 – 10
Abstract
Abstract Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.
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