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Predicting responsiveness to fampridine in gait‐impaired patients with multiple sclerosis
Author(s) -
Filli L.,
Werner J.,
Beyer G.,
Reuter K.,
Petersen J. A.,
Weller M.,
Zörner B.,
Linnebank M.
Publication year - 2019
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13805
Subject(s) - medicine , multiple sclerosis , logistic regression , placebo , crossover study , gait , drug , physical therapy , physical medicine and rehabilitation , pharmacology , psychiatry , alternative medicine , pathology
Background and purpose Fampridine leads to significant improvements in walking in many people with multiple sclerosis (Pw MS ). However, a relevant proportion of Pw MS does not respond to fampridine and predictors of initial drug responsiveness are unknown. Methods Drug response to prolonged‐release ( PR )‐fampridine was assessed in 55 Pw MS using the timed 25‐foot walk (T25FW), 6‐min walk test (6 MWT ) and 12‐item multiple sclerosis walking scale as outcome parameters. Patients were treated with PR ‐fampridine and placebo for 6 weeks each in a randomized, double‐blind, placebo‐controlled trial with crossover design ( NCT 01576354). Possible predictors of drug responsiveness were investigated by multiple correlation analysis and binary logistic regression models. An additional longitudinal analysis followed the drug responses of 32 patients treated with PR ‐fampridine over 3 years to identify potential predictors of long‐term drug responsiveness. Results Severity of walking disability was positively correlated with enhanced responses to PR ‐fampridine. The strongest single predictor of drug responsiveness was poor 6 MWT performance at baseline, which was positively correlated with enhanced drug response in the 6 MWT ( R = −0.541; P < 0.001). A multivariable logistic regression model including 6 MWT and T25FW baseline performances predicted PR ‐fampridine responder status with an accuracy of 85.5% (specificity, 90.0%; sensitivity, 73.3%), with a threshold of 211 m in the 6 MWT best separating responders from non‐responders. Enhanced drug responsiveness after 3 years correlated with decline in walking endurance during this period ( R = −0.634; P = 0.001). Conclusions Initial walking impairment is a good predictor of therapeutic responsiveness to PR ‐fampridine. Valid predictors of patients’ responsiveness to PR ‐fampridine are essential for patient stratification and optimization of multiple slcerosis treatment.