Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10375181" target="_blank" >RIV/00216208:11110/18:10375181 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/18:10375181
Result on the web
<a href="http://dx.doi.org/10.1016/S1474-4422(18)30069-3" target="_blank" >http://dx.doi.org/10.1016/S1474-4422(18)30069-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/S1474-4422(18)30069-3" target="_blank" >10.1016/S1474-4422(18)30069-3</a>
Alternative languages
Result language
angličtina
Original language name
Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension
Original language description
Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18-58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3.0-6.5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3.0-5.5 vs 6.0-6.5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0.86; 95% CI 0.66-1.13; p=0.287). No treatment effect was observed on the EDSS (OR 1.06, 95% CI 0.74-1.53; nominal p=0.753) or the T25FW (0.98, 0.74-1.30; nominal p=0.914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0.56, 95% CI 0.40-0.80; nominal p=0.001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108-221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
The Lancet: Neurology
ISSN
1474-4422
e-ISSN
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Volume of the periodical
17
Issue of the periodical within the volume
5
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
405-415
UT code for WoS article
000429968100016
EID of the result in the Scopus database
2-s2.0-85043460798