Long-term effects of dalfampridine in patients with multiple sclerosis
Department of Neurology - University of Münster, Albert-Schweitzer-Campus 1, Building A 10, 48149 Münster, Germany. Journal of the neurological sciences
(Impact Factor: 2.47).
11/2013; 337(1-2). DOI: 10.1016/j.jns.2013.11.011
Dalfampridine is the extended-release formulation of 4-aminopyridine and is approved for the symptomatic treatment of impaired mobility in patients with multiple sclerosis. Our aim was to examine the short- and long-term effects of treatment with dalfampridine on motoric and cognitive assessment parameters of multiple sclerosis (MS) patients over 9-12months.
Fifty-two patients with MS with an EDSS between 4.0 and 7.0 and impaired mobility were evaluated for parameters of walking ability, MSFC, cognitive and motor fatigue and evoked potentials at treatment initiation with dalfampridine as well as 2weeks and after 9-12months later.
Thirty out of fifty-two patients (~60%) were still on treatment after 9-12months. Two weeks after treatment initiation, significant ameliorations could be found for T25FW, maximum walking distance as well as motoric and cognitive fatigue which still persisted after 9-12months. In contrast significant effects for velocity were observed only after 2weeks, for improvement in PASAT only after 9-12months. A tendency for improvement of somatosensory evoked potentials was found in a subset of patients.
Dalfampridine shows positive short- and long-term effects on motoric and cognitive assessment parameters in an open-label observational study in a cohort of patients with MS.
Available from: Katja Pavsic
- "Fampridine leads to clinical improvement only in certain patients with MS. According to different studies the percentage of so-called responsive patients (responders) ranges from 30% to 74%    . Responsiveness to fampridine is determined after 14 days of treatment based on 20%  or 25%  improvement of walking speed at Timed 25 Foot Walk test (T25FW). "
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Previous studies have predominantly investigated the effect of fampridine on lower extremities motor functions while data on its impact on other symptoms of multiple sclerosis (MS) are scarce. The aim of our study was to assess the impact of fampridine on walking, arm/hand function, fatigue, cognitive function, mood and quality of life among responders.
Our prospective non-randomized study included 30 patients with different types of MS, aged 35-70, EDSS value 3.5-6.5. They were treated with 10mg of fampridine twice daily. The examinations were performed before the treatment, after 14 days, when responders were defined by T25FW (Timed 25-Foot Walk) and 2-min walk test (2MWT) was performed, and after 28 days of treatment, when only the responders were examined. Standardized protocols and questionnaires were used to evaluate the impact of fampridine on walking speed (T25FW, 2MWT), arm/hand function (9-HPT - Nine-Hole Peg Test), cognitive function (PASAT - Paced Auditory Serial Addition Test), total MSFC score (Multiple Sclerosis Functional Composite), fatigue (MFIS - Modified Fatigue Impact Scale), mood (BDI - Beck Depression Inventory) and quality of life (EQ-5D index, EQ-VAS - Euro Quality of Life - 5 Dimension questionnaire and visual analogue scale) in responders.
Response rate was 56.7%. Average improvement of T25FW and 2MWT after 14 days of treatment in responders was 3.6s (34.5%) and 37.4m (42.3%), respectively. This improvement persisted after 28 days of treatment. In non-responders there was no significant improvement of T25FW after 14 days (p=0.689), but there was improvement of 2MWT for 13.4m (14.3%) (p=0.000). After 28 days of treatment significant improvement among responders occurred in total MSFC score (p=0.001), 9-HPT (p=0.002), BDI (p=0.005), MFIS total score (p=0.003), physical (p=0.001), cognitive (p=0.008) MFIS subscales, and EQ-5D index (p=0.012). There were implied trends towards improvement in EQ-VAS and psychosocial MFIS subscale, yet not significant (p=0.057 and p=0.127, respectively). There was no statistically significant improvement of PASAT (p=0.432).
The results of our study highlight the potential of fampridine for improving not only walking speed but also arm/hand function, physical and cognitive fatigue, mood and quality of life. There was no objective improvement of cognitive function. Further placebo-controlled studies will be needed for precise definition of fampridine's action beyond its impact on walking.
Available from: Claire Koenig
- "Prior to designing our study, little evidence existed to support the use of D-ER for improvement of dexterity. Since then, one study failed to find improvement on 9HPT after 2 weeks and after 9-12 months of treatment with D-ER . Our study, however, supports other recent research  showing improvement in 9HPT performance and expands on these findings by also observing gross dexterity performance, lengthening the observation duration, and examining whether performance response varies based on traditional timed walk response. "
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ABSTRACT: Dalfampridine extended release 10mg tablets (D-ER) have demonstrated improvement in walking for ambulatory persons with multiple sclerosis (pwMS), termed "responders."
This study examined the extent additional aspects of gait and dexterity change for patients prescribed D-ER.
Over 14-weeks, walking endurance, dynamic gait, self-report walking ability andfine and gross dexterity were examined in pwMS prescribed D-ER as a part of routine clinical care.
The final results (n=39) validate that a subset of pwMS improve walking speed (Time 25-Foot Walk Test, p<0.0001). Significant improvements in gait and dexterity were observed even among participants who did not improve walking speed. Improvements were evident in gait and dexterity domains including Six Minute Walk Test, p=0.007, Six-Spot Step Test, p<0.0001, Multiple Sclerosis Walking Scale-12, p<0.0001, Nine Hole Peg Test, p<0.0001 dominant and non-dominant sides, and Box and Blocks Test, p=0.005 and 0.002, dominant and non-dominant sides, respectively.
These findings suggest that D-ER may be a potential treatment for gait impairments, beyond walking speed and dexterity in pwMS. Further investigation regarding D-ER response is warranted.
Copyright © 2015 Elsevier B.V. All rights reserved.
Available from: Luca Prosperini
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ABSTRACT: We report a 14-week post-marketing experience on 20 patients with multiple sclerosis (MS) who started prolonged-release (PR) oral dalfampridine 10 mg twice daily according to European Medicine Agency criteria. They underwent serial static posturography assessments and the dizziness handicap inventory (DHI) to investigate whether PR dalfampridine could impact standing balance and self-reported perception of balance. The incidence of accidental falls per person per month was also recorded throughout the study. Eight (40%) patients, who had a relevant improvement in walking speed, were defined as treatment responders. They showed a significant improvement of standing balance (with respect to pretreatment assessment) when contrasted with 12 (60%) nonresponders (F [4,15] = 3.959, P = 0.027). No significant changes in DHI score, as well as in its functional, physical, and emotional subscales, were found in both responders and nonresponders at the end of study (all P values are ≥0.2). Treatment response did not affect the incidence of accidental falls. Future studies based on larger sample sizes, and with longer followup, are required to confirm the beneficial effect of PR dalfampridine on standing balance.
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