TY - JOUR
T1 - Assessment of Clinically Meaningful Improvements in Self-Reported Walking Ability in Participants with Multiple Sclerosis
T2 - Results from the Randomized, Double-Blind, Phase III ENHANCE Trial of Prolonged-Release Fampridine
AU - Hobart, Jeremy
AU - Ziemssen, Tjalf
AU - Feys, Peter
AU - Linnebank, Michael
AU - Goodman, Andrew D.
AU - Farrell, Rachel
AU - Hupperts, Raymond
AU - Blight, Andrew R.
AU - Englishby, Veronica
AU - McNeill, Manjit
AU - Chang, Ih
AU - Lima, Gabriel
AU - Elkins, Jacob
AU - ENHANCE Study Investigators
N1 - Funding Information:
Funding This study was funded by Biogen. Biogen provided funding for medical writing support in the development of this paper; Malcolm Darkes and Juliet Bell from Excel Scientific Solutions wrote the first draft of the manuscript based on input from authors, and Kris-ten DeYoung of Excel Scientific Solutions copyedited and styled the manuscript per journal requirements. Biogen reviewed and provided feedback on the paper to the authors. The authors had full editorial control of the paper, and provided their final approval of all content. The open access fee was paid by Biogen.
Publisher Copyright:
© 2018, The Author(s).
PY - 2019/1
Y1 - 2019/1
N2 - BackgroundWalking 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.ObjectiveThe 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.MethodsENHANCE was a phase III, randomized, double-blind, placebo-controlled study of PR-fampridine 10mg twice daily in walking-impaired individuals age 18-70years 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 24weeks. Secondary endpoints included the proportion with15% 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 24weeks.ResultsIn 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 24weeks 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 a15% improvement in TUG speed, and there was significantly greater mean improvement in MSIS-29 PHYS score (p
AB - BackgroundWalking 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.ObjectiveThe 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.MethodsENHANCE was a phase III, randomized, double-blind, placebo-controlled study of PR-fampridine 10mg twice daily in walking-impaired individuals age 18-70years 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 24weeks. Secondary endpoints included the proportion with15% 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 24weeks.ResultsIn 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 24weeks 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 a15% improvement in TUG speed, and there was significantly greater mean improvement in MSIS-29 PHYS score (p
KW - IMPACT-SCALE MSIS-29
KW - BERG BALANCE SCALE
KW - ABILHAND QUESTIONNAIRE
KW - MANUAL ABILITY
KW - DALFAMPRIDINE
KW - RELIABILITY
KW - EFFICACY
KW - PEOPLE
KW - GAIT
KW - RESPONSIVENESS
U2 - 10.1007/s40263-018-0586-5
DO - 10.1007/s40263-018-0586-5
M3 - Article
SN - 1172-7047
VL - 33
SP - 61
EP - 79
JO - Cns Drugs
JF - Cns Drugs
IS - 1
ER -