Astrid Pechmann1, Max Behrens2, Katharina Dörnbrack3, Adrian Tassoni3, Franziska Wenzel3, Sabine Stein4, Sibylle Vogt4, Daniela Zöller2, Günther Bernert5, Tim Hagenacker6, Ulrike Schara-Schmidt7, Maggie C Walter8, Astrid Bertsche9, Katharina Vill10, Matthias Baumann11, Manuela Baumgartner12, Isabell Cordts13, Astrid Eisenkölbl14, Marina Flotats-Bastardas15, Johannes Friese16, René Günther17, Andreas Hahn18, Veronka Horber19, Ralf A Husain20, Sabine Illsinger21, Jörg Jahnel22, Jessika Johannsen23, Cornelia Köhler24, Heike Kölbel7, Monika Müller25, Arpad von Moers26, Annette Schwerin-Nagel27, Christof Reihle28, Kurt Schlachter29, Gudrun Schreiber30, Oliver Schwartz31, Martin Smitka32, Elisabeth Steiner33, Regina Trollmann34, Markus Weiler35, Claudia Weiß36, Gert Wiegand37, Ekkehard Wilichowski38, Andreas Ziegler39, Hanns Lochmüller4,40, Janbernd Kirschner4. 1. Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Mathildenstr. 1, Freiburg, Germany. astrid.pechmann@uniklinik-freiburg.de. 2. Faculty of Medicine, Institute of Medical Biometry and Statistics, Medical Center - University of Freiburg, Freiburg, Germany. 3. Clinical Trials Unit, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany. 4. Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Mathildenstr. 1, Freiburg, Germany. 5. Department of Pediatrics, Clinic Favoriten, Vienna, Austria. 6. Department of Neurology, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany. 7. Department of Neuropediatrics and Neuromuscular Centre for Children and Adolescents, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, Essen, Germany. 8. Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich, Munich, Germany. 9. University Hospital for Children and Adolescents, Ernst-Heydemann-Straße 8, 18057, Rostock, Germany. 10. 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, Munich, Germany. 11. Division of Pediatric Neurology, Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria. 12. Department of Pediatrics and Adulescent Medicine, Ordensklinikum Linz, Barmherzige Schwestern, Linz, Austria. 13. Department of Neurology, Technical University of Munich, School of Medicine, Munich, Germany. 14. Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Kepler University Hospital, Krankenhausstrasse 26-30, 4020, Linz, Austria. 15. Department of Pediatric Neurology, Saarland University Hospital, Homburg, Germany. 16. Department of Neuropediatrics, University Hospital Bonn, Bonn, Germany. 17. Department of Neurology, University Hospital Carl Gustav Carus, Dresden, Germany. 18. Department of Child Neurology, Justus-Liebig University, Giessen, Germany. 19. Department of Paediatric Neurology, University Children's Hospital, Tübingen, Germany. 20. Department of Neuropediatrics, Jena University Hospital, Jena, Germany. 21. Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical School, Hannover, Germany. 22. Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, LKH Klagenfurt, Medical University of Graz, Graz, Austria. 23. Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 24. Abteilung Für Neuropädiatrie Und Sozialpädiatrie, Universitätsklinik Für Kinder- Und Jugendmedizin, St. Josef-Hospital, Ruhr-Universität Bochum, Bochum, Germany. 25. Department of Neuropediatrics, University Children's Hospital Würzburg, Würzburg, Germany. 26. Department of Pediatrics Und Neuropediatrics, DRK Kliniken Berlin, Berlin, Germany. 27. Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria. 28. Department for Pediatric Neurology, Center for Child and Adolescent Medicine Olgahospital, Psychosomatic and Pain Medicine, Child Pain Center Baden-Württemberg, Klinikum Stuttgart, Stuttgart, Germany. 29. Department of Pediatrics, State Hospital of Bregenz, Bregenz, Austria. 30. Department of Pediatric Neurology, Klinikum Kassel, Kassel, Germany. 31. Department of Pediatric Neurology, Münster University Hospital, Münster, Germany. 32. Abteilung Neuropaediatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 33. Department of Pediatrics and Adolescent Medicine, Johannes Kepler University/Hospital, Linz, Austria. 34. Division of Pediatric Neurology, Department of Pediatrics, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany. 35. Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany. 36. Department of Pediatric Neurology and Center for Chronically Sick Children, Charité - University Medicine Berlin, Augustenburger Platz 1, Berlin, Germany. 37. Neuropediatrics Section of the Department of Pediatrics, Asklepios Clinic Hamburg Nord-Heidberg, Hamburg, Germany. 38. Department of Paediatrics and Pediatric Neurology, University Medical Centre, Georg August University Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Germany. 39. Department of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany. 40. Children's Hospital of Eastern Ontario Research Institute, Division of Neurology, Department of Medicine, The Ottawa Hospital; and Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada.
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.
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.
Authors: Michelle A Farrar; Steve Vucic; Heather M Johnston; Desirée du Sart; Matthew C Kiernan Journal: J Pediatr Date: 2012-07-17 Impact factor: 4.406
Authors: Eugenio Mercuri; Basil T Darras; Claudia A Chiriboga; John W Day; Craig Campbell; Anne M Connolly; Susan T Iannaccone; Janbernd Kirschner; Nancy L Kuntz; Kayoko Saito; Perry B Shieh; Már Tulinius; Elena S Mazzone; Jacqueline Montes; Kathie M Bishop; Qingqing Yang; Richard Foster; Sarah Gheuens; C Frank Bennett; Wildon Farwell; Eugene Schneider; Darryl C De Vivo; Richard S Finkel Journal: N Engl J Med Date: 2018-02-15 Impact factor: 91.245
Authors: S Lefebvre; L Bürglen; S Reboullet; O Clermont; P Burlet; L Viollet; B Benichou; C Cruaud; P Millasseau; M Zeviani Journal: Cell Date: 1995-01-13 Impact factor: 41.582