Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy-Reference-Cited by-同舟云学术

Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy

Published:2022-07-20 Issue:2 Volume:146 Page:668-677
ISSN:0006-8950
Container-title:Brain
language:en
Short-container-title:

Author:

Pechmann Astrid¹^ORCID,Behrens Max²,Dörnbrack Katharina³,Tassoni Adrian³,Stein Sabine¹,Vogt Sibylle¹,Zöller Daniela²,Bernert Günther⁴,Hagenacker Tim⁵,Schara-Schmidt Ulrike⁶,Schwersenz Inge⁷,Walter Maggie C⁸,Baumann Matthias⁹,Baumgartner Manuela¹⁰,Deschauer Marcus¹¹,Eisenkölbl Astrid¹²,Flotats-Bastardas Marina¹³,Hahn Andreas¹⁴,Horber Veronka¹⁵,Husain Ralf A¹⁶^ORCID,Illsinger Sabine¹⁷,Johannsen Jessika¹⁸,Köhler Cornelia¹⁹,Kölbel Heike⁶,Müller Monika²⁰,von Moers Arpad²¹,Schlachter Kurt²²,Schreiber Gudrun²³,Schwartz Oliver²⁴,Smitka Martin²⁵,Steiner Elisabeth²⁶,Stögmann Eva²⁷,Trollmann Regina²⁸^ORCID,Vill Katharina²⁹,Weiß Claudia³⁰,Wiegand Gert³¹^ORCID,Ziegler Andreas³²,Lochmüller Hanns¹³³³⁴³⁵,Kirschner Janbernd¹³⁶^ORCID,Abele Thea Beatrice,Andres Barbara,Angelova-Toshkina Daniela,Baum Petra,Baum Tobias,Baur Ute,Becker Benedikt,Behring Bettina,Birsak Theresa,Bellut Julia,Bertsche Astrid,Blankenburg Markus,Blaschek Astrid,Braun Nathalie,Braun Sarah,Burgenmeister Nadine,Claus Nicole,Cordts Isabell,de Vries Heike,Deba Timo,Marina Adela Della,Denecke Jonas,Driemeyer Joenna,Eckenweiler Matthias,Fiedler Barbara,Fischer Michal,Freigang Maren,Friese Johannes,Gaiser Philippa,Gebert Axel,Geitmann Stephanie,Goldhahn Klaus,Grässl Michael,Gröning Kristina,Grosskreutz Julian,Gruber-Sedlmayr Ursula,Guillemot Helene,Günther René,von der Hagen Maja,Hartmann Hans,Hiebeler Miriam,Hobbiebrunken Elke,Hoffmann Georg Friedrich,Holtkamp Britta,Holzwarth Dorothea,Jansen Eva,Kaindl Angela,Kaiser Nadja,Klamroth Jennifer,Koch Jan Christoph,Koelker Stefan,Kolzter Kirsten,Korschinsky Brigitte,Küpper Hanna,Langer Thorsten,Lehnert Ilka,Lingor Paul,Löscher Wolfgang N,Loudovici-Krug Dana,Martakis Kyriakos,Mayer Iris,Metelmann Moritz,Meyer Sascha,Mueller-Kaempffer Katharina,Müller Petra,Müller-Felber Wolfgang,Neuwirth Christoph,Niederschweiberer Johanna,Nolte Anja,Odorfer Thorsten,Omran Heymut,Pauschek Josefine,Pickrodt Katrin,Plecko Barbara,Pühringer Manuel,Quinten Anna Lisa,Rappold Mika,Reihle Christof,Reinhardt Tabea,Rödiger Annekathrin,Roetmann Gerda,Saffari Afshin,Schimmel Mareike,Schneider Joanna,Schoene-Bake Christoph,Schorling David,Schwerin-Nagel Anette,Steinbach Robert,Steuernagel Daniela,Stolte Benjamin,Stoltenburg Corinna,Stüve Burkhard,Theophil Manuela,Thiele Simone,Topakian Raffi,Türk Matthias,van der Stam Lieske,Vollmann Peter,Warken Birgit,Weber Markus,Weiler Markus,Weiss Deike,Weiss Simone,Wenzel Franziska,Wider Sabine,Wiebe Nils,Wilichowski Ekkehard,Wilken Bernd,Wochner Katarzyna,Zeiner Fiona,Zeisler Daniela,Zeller Daniel,Zemlin Michael,

Affiliation:

1. Department of Neuropediatrics and Muscle Disorders, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg , D-79106 Freiburg , Germany

2. Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center—University of Freiburg , D-70196 Freiburg , Germany

3. Clinical Trials Unit, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg , D-79106 Freiburg , Germany

4. Clinic Favoriten, Department of Pediatrics , A-1100 Vienna , Austria

5. Department of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen , Hufelands.tr 55, 45147 Essen , Germany

6. Department of Neuropediatrics and Neuromuscular Centre for children and Adolescents, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen , D-45147 Essen , Germany

7. Deutsche Gesellschaft für Muskelkranke , D-79112 Freiburg , Germany

8. Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich , D-80336 Munich , Germany

9. Department of Pediatrics I, Division of Pediatric Neurology, Medical University of Innsbruck , A-6020 Innsbruck , Austria

10. Ordensklinikum Linz, Barmherzige Schwestern, Department of Pediatrics and Adolescent medicine , A-4020 Linz , Austria

11. Department of Neurology, Technical University of Munich, School of Medicine , D-81675 Munich , Germany

12. Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Kepler University Hospital , 4020 Linz , Austria

13. Department of Pediatric Neurology, Saarland University Hospital , D-66421 Homburg , Germany

14. Department of Child Neurology, Justus-Liebig University , D-35392 Giessen , Germany

15. Department of Paediatric Neurology, University Children’s Hospital , D-72076 Tübingen , Germany

16. Department of Neuropediatrics, Jena University Hospital , D-07747 Jena , Germany

17. Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical School , D-30625 Hannover , Germany

18. Department of Pediatrics, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg , Germany

19. Ruhr-Universität Bochum, St. Josef-Hospital, Universitätsklinik für Kinder- und Jugendmedizin, Abteilung für Neuropädiatrie und Sozialpädiatrie , D-44791 Bochum , Germany

20. Department of Neuropediatrics, University Children’s Hospital Würzburg , D-97080 Würzburg , Germany

21. Department of Pediatrics und Neuropediatrics, DRK Kliniken Berlin , D-14050 Berlin , Germany

22. Department of Pediatrics, State Hospital of Bregenz (LKH Bregenz) , A-6900 Bregenz , Austria

23. Department of Pediatric Neurology, Klinikum Kassel , D-34125 Kassel , Germany

24. Department of Pediatric Neurology, Münster University Hospital , D-48149 Münster , Germany

25. Abteilung Neuropaediatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden , D-01307 Dresden , Germany

26. Department of Pediatrics, Klinikum Wels-Grieskirchen , A-4600 Wels , Austria

27. Department of Pediatrics, LK-Banden-Mödling , A-2340 Mödling , Austria

28. Department of Pediatrics, Division of Pediatric Neurology, Friedrich-Alexander-University of Erlangen-Nürnberg , D-91054 Erlangen , Germany

29. 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 , D-80337 Munich , Germany

30. Department of Pediatric Neurology and Center for Chronically Sick Children, Charité—University Medicine Berlin , Augustenburger Platz 1, D-13353 Berlin , Germany

31. Neuropediatrics Section of the Department of Pediatrics, Asklepios Clinic Hamburg Nord-Heidberg , D-22417 Hamburg , Germany

32. Department of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg , D-69120 Heidelberg , Germany

33. Children’s Hospital of Eastern Ontario Research Institute , Ottawa, ON K1H 8L1 , Canada

34. Division of Neurology, Department of Medicine, The Ottawa Hospital , Ottawa, ON K1H 8L6 , Canada

35. Brain and Mind Research Institute, University of Ottawa , Ottawa, ON K1H 8M5 , Canada

36. Department of Neuropediatrics, University Hospital Bonn, Faculty of Medicine , D-53127 Bonn , Germany

Abstract

Abstract 5q-associated spinal muscular atrophy is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by the European Medicines Agency and Food and Drug Administration for the treatment of spinal muscular atrophy patients, however, long-term experience is still scarce. In contrast to clinical trial data with restricted patient populations and short observation periods, we report here real-world evidence on a broad spectrum of patients with early-onset spinal muscular atrophy treated with nusinersen focusing on effects regarding motor milestones, and respiratory and bulbar insufficiency during the first years of treatment. Within the SMArtCARE registry, all patients under treatment with nusinersen who never had the ability to sit independently before the start of treatment were identified for data analysis. The primary outcome of this analysis was the change in motor function evaluated with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders and motor milestones considering World Health Organization criteria. Further, we evaluated data on the need for ventilator support and tube feeding, and mortality. In total, 143 patients with early-onset spinal muscular atrophy were included in the data analysis with a follow-up period of up to 38 months. We observed major improvements in motor function evaluated with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders. Improvements were greater in children >2 years of age at start of treatment than in older children. 24.5% of children gained the ability to sit independently. Major improvements were observed during the first 14 months of treatment. The need for intermittent ventilator support and tube feeding increased despite treatment with nusinersen. Our findings confirm the increasing real-world evidence that treatment with nusinersen has a dramatic influence on disease progression and survival in patients with early-onset spinal muscular atrophy. Major improvements in motor function are seen in children younger than 2 years at the start of treatment. Bulbar and respiratory function needs to be closely monitored, as these functions do not improve equivalent to motor function.

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

Link

https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awac252/47948542/awac252.pdf

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