Improvements in Walking Distance during Nusinersen Treatment - A Prospective 3-year SMArtCARE Registry Study.


Journal

Journal of neuromuscular diseases
ISSN: 2214-3602
Titre abrégé: J Neuromuscul Dis
Pays: Netherlands
ID NLM: 101649948

Informations de publication

Date de publication:
2023
Historique:
pubmed: 25 12 2022
medline: 11 1 2023
entrez: 24 12 2022
Statut: ppublish

Résumé

Disease progression in patients with spinal muscular atrophy (SMA) has changed dramatically within the past years due to the approval of three different disease-modifying treatments. Nusinersen was the first drug to be approved for the treatment of SMA patients. Clinical trials provided data from infants with SMA type 1 and children with SMA type 2, but there is still insufficient evidence and only scarcely reported long-term experience for nusinersen treatment in ambulant patients. Here, we report data from the SMArtCARE registry of ambulant patients under nusinersen treatment with a follow-up period of up to 38 months. SMArtCARE is a disease-specific registry in Germany, Austria and Switzerland. Data are collected as real-world data during routine patient visits. Our analysis included all patients under treatment with nusinersen able to walk independently before start of treatment with focus on changes in motor function. Data from 231 ambulant patients were included in the analysis. During the observation period, 31 pediatric walkers (27.2%) and 31 adult walkers (26.5%) experienced a clinically meaningful improvement of≥30 m in the 6-Minute-Walk-Test. In contrast, only five adult walkers (7.7%) showed a decline in walking distance≥30 m, and two pediatric walkers (1.8%) lost the ability to walk unassisted under treatment with nusinersen. HFMSE and RULM scores improved in pediatric and remained stable in adult patients. Our data demonstrate a positive effect of nusinersen treatment in most ambulant pediatric and adult SMA patients. We not only observed a stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance.

Sections du résumé

BACKGROUND AND OBJECTIVES OBJECTIVE
Disease progression in patients with spinal muscular atrophy (SMA) has changed dramatically within the past years due to the approval of three different disease-modifying treatments. Nusinersen was the first drug to be approved for the treatment of SMA patients. Clinical trials provided data from infants with SMA type 1 and children with SMA type 2, but there is still insufficient evidence and only scarcely reported long-term experience for nusinersen treatment in ambulant patients. Here, we report data from the SMArtCARE registry of ambulant patients under nusinersen treatment with a follow-up period of up to 38 months.
METHODS METHODS
SMArtCARE is a disease-specific registry in Germany, Austria and Switzerland. Data are collected as real-world data during routine patient visits. Our analysis included all patients under treatment with nusinersen able to walk independently before start of treatment with focus on changes in motor function.
RESULTS RESULTS
Data from 231 ambulant patients were included in the analysis. During the observation period, 31 pediatric walkers (27.2%) and 31 adult walkers (26.5%) experienced a clinically meaningful improvement of≥30 m in the 6-Minute-Walk-Test. In contrast, only five adult walkers (7.7%) showed a decline in walking distance≥30 m, and two pediatric walkers (1.8%) lost the ability to walk unassisted under treatment with nusinersen. HFMSE and RULM scores improved in pediatric and remained stable in adult patients.
CONCLUSION CONCLUSIONS
Our data demonstrate a positive effect of nusinersen treatment in most ambulant pediatric and adult SMA patients. We not only observed a stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance.

Identifiants

pubmed: 36565133
pii: JND221600
doi: 10.3233/JND-221600
pmc: PMC9881023
doi:

Substances chimiques

nusinersen 5Z9SP3X666

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

29-40

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Auteurs

Astrid Pechmann (A)

Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Max Behrens (M)

Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.

Katharina Dörnbrack (K)

Clinical Trials Unit, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Adrian Tassoni (A)

Clinical Trials Unit, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Franziska Wenzel (F)

Clinical Trials Unit, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Sabine Stein (S)

Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Sibylle Vogt (S)

Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Daniela Zöller (D)

Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.

Günther Bernert (G)

Clinic Favoriten, Department of Pediatrics, Vienna, Austria.

Tim Hagenacker (T)

Department of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany.

Ulrike Schara-Schmidt (U)

Department of Neuropediatrics and Neuromuscular Centre for children and Adolescents, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, Essen, Germany.

Maggie C Walter (MC)

Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany.

Meike Steinbach (M)

Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany.

Astrid Blaschek (A)

Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children with Medical Complexity, Dr. von Hauner Children's Hospital, LMU Hospital, Ludwig-Maximilians-University, Munich, Germany.

Matthias Baumann (M)

Department of Pediatrics I, Division of Pediatric Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Manuela Baumgartner (M)

Ordensklinikum Linz, Barmherzige Schwestern, Department of Pediatrics and Adulescent Medicine, Linz, Austria.

Benedikt Becker (B)

Department of Neurology, School of Medicine, Technical University of Munich, Munich, Germany.

Marina Flotats-Bastardas (M)

Department of Pediatric Neurology, Saarland University Hospital, Homburg, Germany.

Johannes Friese (J)

Department of Neuropediatrics, University Hospital Bonn, Bonn, Germany.

Rene Günther (R)

Department of Neurology, University Hospital Carl Gustav Carus, Dresden, Germany.

Andreas Hahn (A)

Department of Child Neurology, Justus-Liebig University, Giessen, Germany.

Hanna Küpper (H)

Department of Paediatric Neurology, University Children's Hospital, Tübingen, Germany.

Jessika Johannsen (J)

Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Christoph Kamm (C)

Department of Neurology, University of Rostock, Rostock, Germany.

Jan Christoph Koch (JC)

Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.

Cornelia Köhler (C)

Ruhr-Universität Bochum, St. Josef-Hospital, Abteilung für Neuropädiatrie und Sozialpädiatrie, Universitätsklinik für Kinder- und Jugendmedizin, Bochum, Germany.

Heike Kölbel (H)

Department of Neuropediatrics and Neuromuscular Centre for children and Adolescents, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, Essen, Germany.

Kirsten Kolzter (K)

Children's Hospital Amsterdamer Straße, Kliniken der Stadt Köln, Cologne, Germany.

Arpad von Moers (A)

Department of Pediatrics und Neuropediatrics, DRK Kliniken Berlin, Berlin, Germany.

Steffen Naegel (S)

Department of Neurology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

Christoph Neuwirth (C)

Neuromuscular Diseases Unit / ALS Clinic, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Susanne Petri (S)

Department of Neurology, Hannover Medical School, Hannover, Germany.

Annekathrin Rödiger (A)

Department of Neurology, University Hospital Jena, Jena, Germany.

Mareike Schimmel (M)

Pediatrics and Adolescent Medicine, Pediatric Neurology, University Medical Center Augsburg, Augsburg, Germany.

Bertold Schrank (B)

Fachbereich Neurologie, DKD Helios Klinik Wiesbaden, Wiesbaden, Germany.

Gudrun Schreiber (G)

Department of Pediatric Neurology, Klinikum Kassel, Kassel, Germany.

Martin Smitka (M)

Abteilung Neuropaediatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Christian Stadler (C)

Department of Neurology, Klinikum Klagenfurt am Wörthersee, Klagenfurt am Wörthersee, Austria.

Elisabeth Steiner (E)

Department of Pediatrics and Adolescent Medicine, Johannes Kepler University / Hospital, Linz, Austria.

Eva Stögmann (E)

Department of Pediatrics, Landesklinikum Baden-Mödling, Standort Mödling, Germany.

Regina Trollmann (R)

Department of Pediatrics, Division of Pediatric Neurology, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany.

Matthias Türk (M)

Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Germany.

Markus Weiler (M)

Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

Corinna Stoltenburg (C)

Department of Pediatric Neurology and Center for Chronically Sick Children, Charité - University Medicine Berlin, Berlin, Germany.

Ekkehard Willichowsky (E)

Department of Paediatrics and Pediatric Neurology, University Medical Centre, Georg August University Göttingen, Göttingen, Germany.

Daniel Zeller (D)

Department of Neurology, University Hospital Würzburg, Würzburg, Germany.

Andreas Ziegler (A)

Department of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Hanns Lochmüller (H)

Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada.
Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.

Janbernd Kirschner (J)

Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

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