Hagenacker, Tim, Wurster, Claudia D., Guenther, Rene, Schreiber-Katz, Olivia, Osmanovic, Alma, Petri, Susanne, Weiler, Markus, Ziegler, Andreas, Kuttler, Josua, Koch, Jan C., Schneider, Ilka, Wunderlich, Gilbert, Schloss, Natalie, Lehmann, Helmar C., Cordts, Isabell, Deschauer, Marcus, Lingor, Paul ORCID: 0000-0001-9362-7096, Kamm, Christoph, Stolte, Benjamin, Pietruck, Lena, Totzeck, Andreas, Kizina, Kathrin, Monninghoff, Christoph, von Velsen, Otgonzul, Ose, Claudia, Reichmann, Heinz, Forsting, Michael, Pechmann, Astrid, Kirschner, Janbernd, Ludolph, Albert C., Hermann, Andreas and Kleinschnitz, Christoph (2020). Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Lancet Neurol., 19 (4). S. 317 - 326. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1474-4465

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Abstract

Background Nusinersen is approved for the treatment of 5q spinal muscular atrophy of all types and stages in patients of all ages. Although clinical trials have shown improvements in motor function in infants and children treated with the drug, data for adults are scarce. We aimed to assess the safety and efficacy of nusinersen in adults with 5q spinal muscular atrophy. Methods We did an observational cohort study at ten academic clinical sites in Germany. Patients with genetically confirmed 5q spinal muscular atrophy (age 16-65 years) with a homozygous deletion of exons 7, 8, or both, or with compound heterozygous mutations were eligible for inclusion and received nusinersen treatment in accordance with the label for a minimum treatment time of 6 months to a follow-up of up to 14 months. The primary outcome was the change in the total Hammersmith Functional Motor Scale Expanded (HFMSE) score, assessed at months 6, 10, and 14, and based on pre-post comparisons. This study is registered with the German Clinical Trials Register (number DRKS00015702). Findings Between July 13, 2017, and May 1, 2019, 173 patients were screened, of whom 139 (80%) were eligible for data analysis. Of these, 124 (89%) were induded in the 6-month analysis, 92 (66%) in the 10-month analysis, and 57 (41%) in the 14-month analysis; patients with missing baseline HFMSE scores were excluded from these analyses. Mean HFMSE scores were significantly increased compared with baseline at 6 months (mean difference 1.73 [95% CI 1.05-2.411, p<0.0001), 10 months (2.58 [1- 76-3.39], p<0.001), and 14 months (3.12 [2.06-4.19], p<0.0001). Clinically meaningful improvements (>= 3 points increase) in HFMSE scores were seen in 35 (28%) of 124 patients at 6 months, 33 (35%) of 92 at 10 months, and 23 (40%) of 57 at 14 months. To 14-month follow-up, the most frequent adverse effects among 173 patients were headache (61[35%] patients), back pain (38[22%]), and nausea (19 [11%]). No serious adverse events were reported. Interpretation Despite the limitations of the observational study design and a slow functional decline throughout the natural disease course, our data provide evidence for the safety and efficacy of nusinersen in the treatment of adults with 5q spinal muscular atrophy, with clinically meaningful improvements in motor function in a real-world cohort.Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hagenacker, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wurster, Claudia D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenther, ReneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber-Katz, OliviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osmanovic, AlmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petri, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiler, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziegler, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuttler, JosuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, Jan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, IlkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, GilbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schloss, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, Helmar C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cordts, IsabellUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deschauer, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lingor, PaulUNSPECIFIEDorcid.org/0000-0001-9362-7096UNSPECIFIED
Kamm, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stolte, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietruck, LenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Totzeck, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kizina, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monninghoff, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Velsen, OtgonzulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ose, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reichmann, HeinzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forsting, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pechmann, AstridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirschner, JanberndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ludolph, Albert C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hermann, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleinschnitz, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-339602
Journal or Publication Title: Lancet Neurol.
Volume: 19
Number: 4
Page Range: S. 317 - 326
Date: 2020
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1474-4465
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SHAM CONTROLMultiple languages
Clinical NeurologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33960

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