Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study

被引：227

作者：

Hagenacker, Tim ^{[1
]}

Wurster, Claudia D. ^{[5
]}

Guenther, Rene ^{[6
,19
]}

Schreiber-Katz, Olivia ^{[7
]}

Osmanovic, Alma ^{[7
]}

Petri, Susanne ^{[7
]}

Weiler, Markus ^{[8
]}

Ziegler, Andreas ^{[9
]}

Kuttler, Josua ^{[10
]}

Koch, Jan C. ^{[10
]}

Schneider, Ilka ^{[11
]}

Wunderlich, Gilbert ^{[12
,13
,14
]}

Schloss, Natalie ^{[12
]}

Lehmann, Helmar C. ^{[12
]}

Cordts, Isabell ^{[15
]}

Deschauer, Marcus ^{[15
]}

Lingor, Paul ^{[15
]}

Kamm, Christoph ^{[16
]}

Stolte, Benjamin ^{[1
]}

Pietruck, Lena ^{[1
]}

Totzeck, Andreas ^{[1
]}

Kizina, Kathrin ^{[1
]}

Monninghoff, Christoph ^{[2
]}

von Velsen, Otgonzul ^{[3
,4
]}

Ose, Claudia ^{[3
,4
]}

Reichmann, Heinz ^{[6
]}

Forsting, Michael ^{[2
]}

Pechmann, Astrid ^{[17
]}

Kirschner, Janbernd ^{[17
,18
]}

Ludolph, Albert C. ^{[5
,20
]}

Hermann, Andreas ^{[16
,21
,22
]}

Kleinschnitz, Christoph ^{[1
]}

机构：

[1] Univ Hosp Essen, Dept Neurol, D-45127 Essen, Germany

[2] Univ Hosp Essen, Dept Diagnost & Intervent Radiol & Neuroradiol, Essen, Germany

[3] Univ Hosp Essen, Inst Med Informat Biometr & Epidemiol, Essen, Germany

[4] Univ Hosp Essen, Ctr Clin Trials, Essen, Germany

[5] Ulm Univ, Dept Neurol, Ulm, Germany

[6] Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Dept Neurol, Dresden, Germany

[7] Hannover Med Sch, Dept Neurol, Hannover, Germany

[8] Heidelberg Univ Hosp, Dept Neurol, Heidelberg, Germany

[9] Heidelberg Univ Hosp, Ctr Child & Adolescent Med, Div Child Neurol & Metab Med, Heidelberg, Germany

[10] Univ Med Gottingen, Dept Neurol, Gottingen, Germany

[11] Univ Hosp Halle Saale, Dept Neurol, Halle, Saale, Germany

[12] Univ Cologne, Fac Med, Dept Neurol, Cologne, Germany

[13] Univ Cologne, Fac Med, Ctr Rare Dis, Cologne, Germany

[14] Univ Cologne, Univ Hosp Cologne, Cologne, Germany

[15] Tech Univ Munich, Dept Neurol, Klinikum Rechts Isar, Munich, Germany

[16] Univ Rostock, Dept Neurol, Rostock, Germany

[17] Med Ctr Univ Freiburg, Fac Med, Dept Neuropediat & Muscle Disorders, Freiburg, Germany

[18] Univ Med Ctr Bonn, Dept Neuropediat, Bonn, Germany

[19] German Ctr Neurodegenerat Dis Dresden, Dresden, Germany

[20] German Ctr Neurodegenerat Dis Ulm, Ulm, Germany

[21] Univ Rostock, Univ Med Ctr Rostock, Dept Neurol, Translat Neurodegenerat Sect Albrecht Kosser, Rostock, Germany

[22] German Ctr Neurodegenerat Dis Rostock, Rostock, Germany

来源：

LANCET NEUROLOGY | 2020年 / 19卷 / 04期

关键词：

SHAM CONTROL;

D O I：

10.1016/S1474-4422(20)30037-5

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：317 / 325

页数：9

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