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dc.contributor.authorHobart, JC
dc.contributor.authorZiemssen, T
dc.contributor.authorFeys, P
dc.contributor.authorLinnebank, M
dc.contributor.authorGoodman, AD
dc.contributor.authorFarrell, R
dc.contributor.authorHupperts, R
dc.contributor.authorBlight, AR
dc.contributor.authorEnglishby, V
dc.contributor.authorMcNeill, M
dc.contributor.authorChang, I
dc.contributor.authorElkins, J
dc.date.accessioned2018-10-24T09:54:30Z
dc.date.issued2019-01
dc.identifier.issn1179-1934
dc.identifier.issn1179-1934
dc.identifier.urihttp://hdl.handle.net/10026.1/12608
dc.descriptionFile replaced (docx to pdf) on 26.4.23 by NK
dc.description.abstract

BACKGROUND: Walking impairment is a hallmark of multiple sclerosis (MS). It affects > 90% of individuals over time, reducing independence and negatively impacting health-related quality of life, productivity, and daily activities. Walking impairment is consistently reported as one of the most distressing impairments by individuals with MS. Prolonged-release (PR)-fampridine previously has been shown to improve objectively measured walking speed in walking-impaired adults with MS. The impact of PR-fampridine from the perspective of the individual with MS warrants full and detailed examination. OBJECTIVE: The objective of this study was to evaluate whether PR-fampridine has a clinically meaningful effect on self-reported walking ability in walking-impaired participants with MS. METHODS: ENHANCE was a phase III, randomized, double-blind, placebo-controlled study of PR-fampridine 10 mg twice daily in walking-impaired individuals age 18-70 years with either relapsing or progressive forms of MS and an Expanded Disability Status Scale (EDSS) score of 4.0-7.0 at screening. Participants were stratified by EDSS score (≤ 6.0 or 6.5-7.0) at randomization to ensure a balanced level of disability in the treatment groups. The primary endpoint was the proportion of participants with a mean improvement in the 12-item Multiple Sclerosis Walking Scale (MSWS-12) score exceeding the predefined threshold for clinically meaningful improvement (≥ 8 points) over 24 weeks. Secondary endpoints included the proportion with ≥ 15% improvement in Timed Up and Go (TUG) speed, and mean changes in Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS), Berg Balance Scale (BBS), and ABILHAND scores over 24 weeks. RESULTS: In total, 636 participants with MS were randomized (PR-fampridine, n = 317; placebo, n = 319; modified intention-to-treat sample: PR-fampridine, n = 315; placebo, n = 318). At baseline in the PR-fampridine and placebo groups, 46% and 51% had a progressive form of MS, median [range] EDSS scores were 6.0 [4.0-7.0] and 5.5 [4.0-7.0], mean [range] MSWS-12 scores were 63.6 [0-100] and 65.4 [0-100], and mean [range] TUG speed was 0.38 [0.0-1.0] and 0.38 [0.0-1.2] feet/s, respectively. A significantly higher percentage of PR-fampridine-treated participants (136/315 [43.2%]) had clinically meaningful improvement in MSWS-12 score over 24 weeks versus placebo (107/318 [33.6%]; odds ratio 1.61 [95% confidence interval 1.15-2.26]; p = 0.006). For PR-fampridine versus placebo, significantly more participants had a ≥ 15% improvement in TUG speed, and there was significantly greater mean improvement in MSIS-29 PHYS score (p < 0.05); numerical improvements that were not statistically significant were observed in BBS/ABILHAND. Adverse events that were more common in the PR-fampridine group than placebo group (difference ≥ 3%) by Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Term were urinary tract infection and insomnia. There were no seizures reported. CONCLUSIONS: PR-fampridine treatment resulted in sustained, clinically meaningful improvements over 24 weeks in self-reported walking and functional ability in walking-disabled participants with MS. CLINICALTRIALS. GOV IDENTIFIER: NCT02219932.

dc.format.extent61-79
dc.format.mediumPrint
dc.languageen
dc.language.isoen
dc.publisherSpringer Verlag
dc.subject4-Aminopyridine
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectDouble-Blind Method
dc.subjectFemale
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMultiple Sclerosis
dc.subjectQuality of Life
dc.subjectSelf Report
dc.subjectWalking
dc.subjectYoung Adult
dc.titleAssessment of Clinically Meaningful Improvements in Self-Reported Walking Ability in Participants with Multiple Sclerosis: Results from the Randomized, Double-blind, Phase III ENHANCE Trial of Prolonged-release Fampridine
dc.typejournal-article
dc.typeClinical Trial, Phase III
dc.typeJournal Article
dc.typeMulticenter Study
dc.typeRandomized Controlled Trial
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000455498500006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue1
plymouth.volume33
plymouth.publication-statusPublished
plymouth.journalCNS Drugs
dc.identifier.doi10.1007/s40263-018-0586-5
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA03 Allied Health Professions, Dentistry, Nursing and Pharmacy
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CCT&PS
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeNew Zealand
dcterms.dateAccepted2018-10-24
dc.rights.embargodate2019-2-12
dc.identifier.eissn1179-1934
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1007/s40263-018-0586-5
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-01
rioxxterms.typeJournal Article/Review


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