Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study

Günther R, Wurster CD, Brakemeier S, Osmanovic A, Schreiber-Katz O, Petri S, Uzelac Z, Hiebeler M, Thiele S, Walter MC, Weiler M, Kessler T, Freigang M, Lapp HS, Cordts I, Lingor P, Deschauer M, Hahn A, Martakis K, Steinbach R, Ilse B, Rödiger A, Bellut J, Nentwich J, Zeller D, Muhandes MT, Baum T, Christoph Koch J, Schrank B, Fischer S, Hermann A, Kamm C, Naegel S, Mensch A, Weber M, Neuwirth C, Lehmann HC, Wunderlich G, Stadler C, Tomforde M, George A, Groß M, Pechmann A, Kirschner J, Türk M, Schimmel M, Bernert G, Martin P, Rauscher C, Meyer zu Hörste G, Baum P, Löscher W, Flotats-Bastardas M, Köhler C, Probst-Schendzielorz K, Goldbach S, Schara-Schmidt U, Müller-Felber W, Lochmüller H, von Velsen O, Kleinschnitz C, Ludolph AC, Hagenacker T (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 39

Article Number: 100862

DOI: 10.1016/j.lanepe.2024.100862

Abstract

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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Ulm Germany (DE) Universitätsklinikum Essen Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Klinikum der Universität München (LMU Klinikum) Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Kantonsspital St.Gallen Switzerland (CH) Universitätsklinikum Köln Germany (DE) Klinikum Klagenfurt am Wörthersee Austria (AT) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Carl von Ossietzky Universität Oldenburg Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Augsburg Germany (DE) Universitätsmedizin Rostock Germany (DE) Universität Rostock Germany (DE) Justus-Liebig-Universität Gießen Germany (DE) Universitätsklinikum Jena Germany (DE) Technische Universität München (TUM) Germany (DE) Hertie-Institut für klinische Hirnforschung Germany (DE) Paracelsus Medizinische Privatuniversität Austria (AT) Universitätsklinikum Münster Germany (DE) Universität Leipzig Germany (DE) Medizinische Universität Innsbruck Austria (AT) Ruhr-Universität Bochum (RUB) Germany (DE) Initiative „Forschung und Therapie für die Spinale Muskelatrophie“ im Förderverein für die Deutsche Gesellschaft für Muskelkranke e.V. (Initiative SMA) Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Göttingen Germany (DE) Deutsche Klinik für Diagnostik Germany (DE) Universitätsklinikum Halle (Saale) Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE)

How to cite

APA:

Günther, R., Wurster, C.D., Brakemeier, S., Osmanovic, A., Schreiber-Katz, O., Petri, S.,... Hagenacker, T. (2024). Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study. The Lancet Regional Health - Europe, 39. https://doi.org/10.1016/j.lanepe.2024.100862

MLA:

Günther, René, et al. "Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study." The Lancet Regional Health - Europe 39 (2024).

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