Assessment 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.contributor.author | Hobart, JC | |
dc.contributor.author | Ziemssen, T | |
dc.contributor.author | Feys, P | |
dc.contributor.author | Linnebank, M | |
dc.contributor.author | Goodman, AD | |
dc.contributor.author | Farrell, R | |
dc.contributor.author | Hupperts, R | |
dc.contributor.author | Blight, AR | |
dc.contributor.author | Englishby, V | |
dc.contributor.author | McNeill, M | |
dc.contributor.author | Chang, I | |
dc.contributor.author | Elkins, J | |
dc.date.accessioned | 2018-10-24T09:54:30Z | |
dc.date.issued | 2019-01 | |
dc.identifier.issn | 1179-1934 | |
dc.identifier.issn | 1179-1934 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/12608 | |
dc.description | File 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.extent | 61-79 | |
dc.format.medium | ||
dc.language | en | |
dc.language.iso | en | |
dc.publisher | Springer Verlag | |
dc.subject | 4-Aminopyridine | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Double-Blind Method | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Middle Aged | |
dc.subject | Multiple Sclerosis | |
dc.subject | Quality of Life | |
dc.subject | Self Report | |
dc.subject | Walking | |
dc.subject | Young Adult | |
dc.title | Assessment 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.type | journal-article | |
dc.type | Clinical Trial, Phase III | |
dc.type | Journal Article | |
dc.type | Multicenter Study | |
dc.type | Randomized Controlled Trial | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000455498500006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 1 | |
plymouth.volume | 33 | |
plymouth.publication-status | Published | |
plymouth.journal | CNS Drugs | |
dc.identifier.doi | 10.1007/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.place | New Zealand | |
dcterms.dateAccepted | 2018-10-24 | |
dc.rights.embargodate | 2019-2-12 | |
dc.identifier.eissn | 1179-1934 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1007/s40263-018-0586-5 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2019-01 | |
rioxxterms.type | Journal Article/Review |