The Lancet Regional Health. Europe (Apr 2024)
Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context
- René Günther,
- Claudia Diana Wurster,
- Svenja Brakemeier,
- Alma Osmanovic,
- Olivia Schreiber-Katz,
- Susanne Petri,
- Zeljko Uzelac,
- Miriam Hiebeler,
- Simone Thiele,
- Maggie C. Walter,
- Markus Weiler,
- Tobias Kessler,
- Maren Freigang,
- Hanna Sophie Lapp,
- Isabell Cordts,
- Paul Lingor,
- Marcus Deschauer,
- Andreas Hahn,
- Kyriakos Martakis,
- Robert Steinbach,
- Benjamin Ilse,
- Annekathrin Rödiger,
- Julia Bellut,
- Julia Nentwich,
- Daniel Zeller,
- Mohamad Tareq Muhandes,
- Tobias Baum,
- Jan Christoph Koch,
- Bertold Schrank,
- Sophie Fischer,
- Andreas Hermann,
- Christoph Kamm,
- Steffen Naegel,
- Alexander Mensch,
- Markus Weber,
- Christoph Neuwirth,
- Helmar C. Lehmann,
- Gilbert Wunderlich,
- Christian Stadler,
- Maike Tomforde,
- Annette George,
- Martin Groß,
- Astrid Pechmann,
- Janbernd Kirschner,
- Matthias Türk,
- Mareike Schimmel,
- Günther Bernert,
- Pascal Martin,
- Christian Rauscher,
- Gerd Meyer zu Hörste,
- Petra Baum,
- Wolfgang Löscher,
- Marina Flotats-Bastardas,
- Cornelia Köhler,
- Kristina Probst-Schendzielorz,
- Susanne Goldbach,
- Ulrike Schara-Schmidt,
- Wolfgang Müller-Felber,
- Hanns Lochmüller,
- Otgonzul von Velsen,
- Christoph Kleinschnitz,
- Albert C. Ludolph,
- Tim Hagenacker
Affiliations
- René Günther
- Department of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dresden, Dresden, Germany
- Claudia Diana Wurster
- Department of Neurology, Ulm University, Ulm, Germany
- Svenja Brakemeier
- Department of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany
- Alma Osmanovic
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Olivia Schreiber-Katz
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Susanne Petri
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Zeljko Uzelac
- Department of Neurology, Ulm University, Ulm, Germany
- Miriam Hiebeler
- Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
- Simone Thiele
- Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
- Maggie C. Walter
- Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
- Markus Weiler
- Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany
- Tobias Kessler
- Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Maren Freigang
- Department of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany
- Hanna Sophie Lapp
- Department of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany
- Isabell Cordts
- Department of Neurology, Technical University of Munich, School of Medicine, Munich, Germany
- Paul Lingor
- Department of Neurology, Technical University of Munich, School of Medicine, Munich, Germany
- Marcus Deschauer
- Department of Neurology, Technical University of Munich, School of Medicine, Munich, Germany
- Andreas Hahn
- Department of Child Neurology, Justus-Liebig University Gießen, Gießen, Germany
- Kyriakos Martakis
- Department of Child Neurology, Justus-Liebig University Gießen, Gießen, Germany; Department of Pediatrics, Medical Faculty and University Hospital, University of Cologne, Cologne, Germany
- Robert Steinbach
- Department of Neurology, Jena University Hospital, Jena, Germany
- Benjamin Ilse
- Department of Neurology, Jena University Hospital, Jena, Germany
- Annekathrin Rödiger
- Department of Neurology, Jena University Hospital, Jena, Germany
- Julia Bellut
- Department of Neurology, University Hospital Würzburg, Würzburg, Germany
- Julia Nentwich
- Department of Neurology, University Hospital Würzburg, Würzburg, Germany
- Daniel Zeller
- Department of Neurology, University Hospital Würzburg, Würzburg, Germany
- Mohamad Tareq Muhandes
- Department of Neurology, University Medicine Göttingen, Göttingen, Germany
- Tobias Baum
- Department of Neurology, University Medicine Göttingen, Göttingen, Germany
- Jan Christoph Koch
- Department of Neurology, University Medicine Göttingen, Göttingen, Germany
- Bertold Schrank
- Department of Neurology, Deutsche Klinik für Diagnostik HELIOS Clinic of Wiesbaden, Wiesbaden, Germany
- Sophie Fischer
- Translational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, 18147, Rostock, Germany
- Andreas Hermann
- Translational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, 18147, Rostock, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Rostock/Greifswald, Rostock, Germany
- Christoph Kamm
- Department of Neurology, University of Rostock, Rostock, Germany
- Steffen Naegel
- Department of Neurology, University Medicine Halle, Halle (Saale), Germany
- Alexander Mensch
- Department of Neurology, University Medicine Halle, Halle (Saale), Germany
- Markus Weber
- Neuromuscular Diseases Unit/ALS Clinic, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
- Christoph Neuwirth
- Neuromuscular Diseases Unit/ALS Clinic, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
- Helmar C. Lehmann
- Department of Neurology and Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Gilbert Wunderlich
- Department of Neurology and Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Christian Stadler
- Department of Neurology, Klinikum Klagenfurt am Wörthersee, Klagenfurt am Wörthersee, Austria
- Maike Tomforde
- Department of Neurology, University Hospital Kiel, Kiel, Germany
- Annette George
- Department of Pediatric Neurology, Center for Chronically Sick Children, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Martin Groß
- Faculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany; Department of Neurological Intensive Care and Rehabilitation, Evangelisches Krankenhaus Oldenburg, Oldenburg, Germany
- Astrid Pechmann
- Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Janbernd Kirschner
- Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Matthias Türk
- Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Germany
- Mareike Schimmel
- Pediatrics and Adolescent Medicine, Faculty of Medicine University Hospital Augsburg, Augsburg, Germany
- Günther Bernert
- Department of Pediatrics and Pediatric Neurology, Clinic Favoriten, Vienna, Austria
- Pascal Martin
- Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University Hospitals Tubingen, Tubingen, Germany
- Christian Rauscher
- Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria
- Gerd Meyer zu Hörste
- Department of Neurology, University Hospital Münster, Münster, Germany
- Petra Baum
- Department of Neurology, University of Leipzig Medical Centre, Leipzig, Germany
- Wolfgang Löscher
- Division of Neurology, Medical University Innsbruck, Innsbruck, Austria
- Marina Flotats-Bastardas
- Department of Pediatric Neurology, Saarland University Hosptial, Homburg, Germany
- Cornelia Köhler
- Department of Neuropaediatrics, University Children's Hospital, Ruhr-University Bochum, Bochum, Germany
- Kristina Probst-Schendzielorz
- Initiative SMA der Deutschen Gesellschaft für Muskelkranke, Freiburg, Germany
- Susanne Goldbach
- Initiative SMA der Deutschen Gesellschaft für Muskelkranke, Freiburg, Germany
- Ulrike Schara-Schmidt
- Department of Paediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, Center for Translational Neuro- and Behavioral Sciences, University Hospital, University of Duisburg-Essen, Essen, Germany
- Wolfgang Müller-Felber
- Department of Neuropediatrics, Dr. v. Haunersche Kinderklinik, University Children's Hospital, Ludwig-Maximilians-Universität München, München, Germany
- Hanns Lochmüller
- 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, Division of Neurology, Department of Medicine, The Ottawa Hospital; and Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada
- Otgonzul von Velsen
- Institute of Medical Informatics, Biometrics, and Epidemiology, University Hospital Essen, Essen, Germany; Center for Clinical Trials, University Hospital Essen, Essen, Germany
- Christoph Kleinschnitz
- Department of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany
- Albert C. Ludolph
- Department of Neurology, Ulm University, Ulm, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ulm, Ulm, Germany
- Tim Hagenacker
- Department of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany; Corresponding author. Department of Neurology, University Medicine Essen, Hufelandstr. 55, 45127, Essen, Germany.
- Journal volume & issue
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Vol. 39
p. 100862
Abstract
Summary: Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19–2.25]), 26 months (1.20 [95% CI 0.48–1.91]), and 38 months (1.52 [95% CI 0.74–2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43–1.07]), 26 months (mean difference 0.65 [95% CI 0.27–1.03]), and 38 months (mean difference 0.72 [95% CI 0.25–1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34–43.38]), 26 months (mean difference 29.26 m [95% CI 14.87–43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32–54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.
