Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context
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 effic...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-04-01
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| Series: | The Lancet Regional Health. Europe |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666776224000280 |
| _version_ | 1797320879541059584 |
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| author | 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 |
| author_facet | 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 |
| author_sort | René Günther |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T04:49:23Z |
| format | Article |
| id | doaj.art-290d74c1de7d42b58be5fe3b14b68827 |
| institution | Directory Open Access Journal |
| issn | 2666-7762 |
| language | English |
| last_indexed | 2024-03-08T04:49:23Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Lancet Regional Health. Europe |
| spelling | doaj.art-290d74c1de7d42b58be5fe3b14b688272024-02-08T05:18:18ZengElsevierThe Lancet Regional Health. Europe2666-77622024-04-0139100862Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in contextRené Günther0Claudia Diana Wurster1Svenja Brakemeier2Alma Osmanovic3Olivia Schreiber-Katz4Susanne Petri5Zeljko Uzelac6Miriam Hiebeler7Simone Thiele8Maggie C. Walter9Markus Weiler10Tobias Kessler11Maren Freigang12Hanna Sophie Lapp13Isabell Cordts14Paul Lingor15Marcus Deschauer16Andreas Hahn17Kyriakos Martakis18Robert Steinbach19Benjamin Ilse20Annekathrin Rödiger21Julia Bellut22Julia Nentwich23Daniel Zeller24Mohamad Tareq Muhandes25Tobias Baum26Jan Christoph Koch27Bertold Schrank28Sophie Fischer29Andreas Hermann30Christoph Kamm31Steffen Naegel32Alexander Mensch33Markus Weber34Christoph Neuwirth35Helmar C. Lehmann36Gilbert Wunderlich37Christian Stadler38Maike Tomforde39Annette George40Martin Groß41Astrid Pechmann42Janbernd Kirschner43Matthias Türk44Mareike Schimmel45Günther Bernert46Pascal Martin47Christian Rauscher48Gerd Meyer zu Hörste49Petra Baum50Wolfgang Löscher51Marina Flotats-Bastardas52Cornelia Köhler53Kristina Probst-Schendzielorz54Susanne Goldbach55Ulrike Schara-Schmidt56Wolfgang Müller-Felber57Hanns Lochmüller58Otgonzul von Velsen59Christoph Kleinschnitz60Albert C. Ludolph61Tim Hagenacker62Department of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dresden, Dresden, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyDepartment of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyFriedrich Baur Institute at the Department of Neurology, LMU University Hospital, LMU Munich, Munich, GermanyFriedrich Baur Institute at the Department of Neurology, LMU University Hospital, LMU Munich, Munich, GermanyFriedrich Baur Institute at the Department of Neurology, LMU University Hospital, LMU Munich, Munich, GermanyDepartment of Neurology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Neurology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, GermanyDepartment of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, GermanyDepartment of Neurology, Technical University of Munich, School of Medicine, Munich, GermanyDepartment of Neurology, Technical University of Munich, School of Medicine, Munich, GermanyDepartment of Neurology, Technical University of Munich, School of Medicine, Munich, GermanyDepartment of Child Neurology, Justus-Liebig University Gießen, Gießen, GermanyDepartment of Child Neurology, Justus-Liebig University Gießen, Gießen, Germany; Department of Pediatrics, Medical Faculty and University Hospital, University of Cologne, Cologne, GermanyDepartment of Neurology, Jena University Hospital, Jena, GermanyDepartment of Neurology, Jena University Hospital, Jena, GermanyDepartment of Neurology, Jena University Hospital, Jena, GermanyDepartment of Neurology, University Hospital Würzburg, Würzburg, GermanyDepartment of Neurology, University Hospital Würzburg, Würzburg, GermanyDepartment of Neurology, University Hospital Würzburg, Würzburg, GermanyDepartment of Neurology, University Medicine Göttingen, Göttingen, GermanyDepartment of Neurology, University Medicine Göttingen, Göttingen, GermanyDepartment of Neurology, University Medicine Göttingen, Göttingen, GermanyDepartment of Neurology, Deutsche Klinik für Diagnostik HELIOS Clinic of Wiesbaden, Wiesbaden, GermanyTranslational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, 18147, Rostock, GermanyTranslational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, 18147, Rostock, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Rostock/Greifswald, Rostock, GermanyDepartment of Neurology, University of Rostock, Rostock, GermanyDepartment of Neurology, University Medicine Halle, Halle (Saale), GermanyDepartment of Neurology, University Medicine Halle, Halle (Saale), GermanyNeuromuscular Diseases Unit/ALS Clinic, Cantonal Hospital St. Gallen, St. Gallen, SwitzerlandNeuromuscular Diseases Unit/ALS Clinic, Cantonal Hospital St. Gallen, St. Gallen, SwitzerlandDepartment of Neurology and Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyDepartment of Neurology and Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyDepartment of Neurology, Klinikum Klagenfurt am Wörthersee, Klagenfurt am Wörthersee, AustriaDepartment of Neurology, University Hospital Kiel, Kiel, GermanyDepartment of Pediatric Neurology, Center for Chronically Sick Children, Charité-Universitätsmedizin Berlin, Berlin, GermanyFaculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany; Department of Neurological Intensive Care and Rehabilitation, Evangelisches Krankenhaus Oldenburg, Oldenburg, GermanyDepartment of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), GermanyPediatrics and Adolescent Medicine, Faculty of Medicine University Hospital Augsburg, Augsburg, GermanyDepartment of Pediatrics and Pediatric Neurology, Clinic Favoriten, Vienna, AustriaDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University Hospitals Tubingen, Tubingen, GermanyDepartment of Pediatrics, Paracelsus Medical University, Salzburg, AustriaDepartment of Neurology, University Hospital Münster, Münster, GermanyDepartment of Neurology, University of Leipzig Medical Centre, Leipzig, GermanyDivision of Neurology, Medical University Innsbruck, Innsbruck, AustriaDepartment of Pediatric Neurology, Saarland University Hosptial, Homburg, GermanyDepartment of Neuropaediatrics, University Children's Hospital, Ruhr-University Bochum, Bochum, GermanyInitiative SMA der Deutschen Gesellschaft für Muskelkranke, Freiburg, GermanyInitiative SMA der Deutschen Gesellschaft für Muskelkranke, Freiburg, GermanyDepartment 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, GermanyDepartment of Neuropediatrics, Dr. v. Haunersche Kinderklinik, University Children's Hospital, Ludwig-Maximilians-Universität München, München, GermanyDepartment 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, CanadaInstitute of Medical Informatics, Biometrics, and Epidemiology, University Hospital Essen, Essen, Germany; Center for Clinical Trials, University Hospital Essen, Essen, GermanyDepartment of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, GermanyDepartment of Neurology, Ulm University, Ulm, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ulm, Ulm, GermanyDepartment 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.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.http://www.sciencedirect.com/science/article/pii/S2666776224000280Antisense oligonucleotideIntrathecal therapyMotor neuron diseaseNusinersenSpinal muscular atrophy |
| spellingShingle | 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 Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context The Lancet Regional Health. Europe Antisense oligonucleotide Intrathecal therapy Motor neuron disease Nusinersen Spinal muscular atrophy |
| title | Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context |
| title_full | Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context |
| title_fullStr | Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context |
| title_full_unstemmed | Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context |
| title_short | Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context |
| title_sort | long term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy a prospective european multinational observational studyresearch in context |
| topic | Antisense oligonucleotide Intrathecal therapy Motor neuron disease Nusinersen Spinal muscular atrophy |
| url | http://www.sciencedirect.com/science/article/pii/S2666776224000280 |
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