| Title: |
Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study |
| Authors: |
Günther, René; Wurster, Claudia Diana; Brakemeier, Svenja; Osmanovic, Alma; Schreiber-Katz, Olivia; Petri, Susanne; Uzelac, Zeljko; Hiebeler, Miriam; Thiele, Simone; Walter, Maggie C.; Weiler, Markus; Kessler, Tobias; Freigang, Maren; Lapp, Hanna Sophie; Cordts, Isabell; Lingor, Paul; Deschauer, Marcus; Hahn, Andreas; Martakis, Kyriakos; Steinbach, Robert; Ilse, Benjamin; Rödiger, Annekathrin; Bellut, Julia; Nentwich, Julia; Zeller, Daniel; Muhandes, Mohamad Tareq; Baum, Tobias; Koch, Jan Christoph; Schrank, Bertold; Fischer, Sophie; Hermann, Andreas; Kamm, Christoph; Naegel, Steffen; Mensch, Alexander; Weber, Markus; Neuwirth, Christoph; Lehmann, Helmar C.; Wunderlich, Gilbert; Stadler, Christian; Tomforde, Maike; George, Annette; Groß, Martin; Pechmann, Astrid; Kirschner, Janbernd; Türk, Matthias; Schimmel, Mareike; Bernert, Günther; Martin, Pascal; Rauscher, Christian; Meyer zu Hörste, Gerd; Baum, Petra; Löscher, Wolfgang; Flotats-Bastardas, Marina; Köhler, Cornelia; Probst-Schendzielorz, Kristina; Goldbach, Susanne; Schara-Schmidt, Ulrike; Müller-Felber, Wolfgang; Lochmüller, Hanns; Velsen, Otgonzul von; Kleinschnitz, Christoph; Ludolph, Albert C.; Hagenacker, Tim |
| Publication Year: |
2024 |
| Collection: |
University of Duisburg-Essen: DuEPublico (Duisburg Essen Publications online) |
| Subject Terms: |
ScholarlyArticle; ddc:610; Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Neurologie; Medizinische Fakultät » Universitätsklinikum Essen » Center for Translational Neuro- and Behavioral Science (C-TNBS); Medizinische Fakultät » Universitätsklinikum Essen » Zentrum für Kinder- und Jugendmedizin » Klinik für Kinderheilkunde I/Perinatalzentrum » Neuropädiatrie; Medizinische Fakultät » Universitätsklinikum Essen » Institut für Medizinische Informatik; Biometrie und Epidemiologie; Antisense oligonucleotide -- Intrathecal therapy -- Motor neuron disease -- Nusinersen -- Spinal muscular atrophy |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1016/j.lanepe.2024.100862 |
| DOI: |
10.1016/j.lanepe.2024.100862 |
| Availability: |
https://doi.org/10.1016/j.lanepe.2024.100862; https://nbn-resolving.org/urn:nbn:de:hbz:465-20250305-144514-3; https://duepublico2.uni-due.de/receive/duepublico_mods_00082425; https://duepublico2.uni-due.de/servlets/MCRFileNodeServlet/duepublico_derivate_00082702/Lancet_Regional_Health_Europe_2024_39_100862.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.7400950F |
| Database: |
BASE |