Long-term effects of dalfampridine in patients with multiple sclerosis
ABSTRACT 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.
SourceAvailable from: Luca Prosperini[Show abstract] [Hide abstract]
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.03/2014; 2014:802307. DOI:10.1155/2014/802307
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ABSTRACT: Walking impairment is a clinical hallmark of multiple sclerosis (MS). Dalfampridine-ER, an extended-release formulation of dalfampridine (also known by its chemical name, 4-aminopyridine, and its international nonproprietary name, fampridine), was developed to maintain drug plasma levels within a narrow therapeutic window, and assessed for its ability to improve walking in MS. The putative mechanism of action of dalfampridine-ER is restoration of axonal conduction via blockade of the potassium channels that become exposed during axonal demyelination. Two pivotal phase III clinical trials demonstrated that dalfampridine-ER 10-mg tablets administered twice daily improved walking speed and patient-reported perceptions of walking in some patients. Dalfampridine-ER was generally well tolerated, and, at the approved dose, risk of seizure was neither elevated relative to placebo nor higher than the rate in the MS population. Dalfampridine-ER (AMPYRA®) was approved in the United States for the treatment of walking in patients with MS as demonstrated by an increase in walking speed. The use of the dalfampridine-ER is contraindicated in patients with a history of seizure. It is the first pharmacologic therapy for this indication and has been incorporated into clinical management of MS.Annals of the New York Academy of Sciences 08/2014; 1329. DOI:10.1111/nyas.12512 · 4.31 Impact Factor
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ABSTRACT: Introduction: Multiple sclerosis (MS) is the most frequent cause of neurological impairment and sustained disability in young adults. Currently approved disease-modifying drugs do not directly ameliorate the most common symptoms, such as walking impairment. Dalfampridine (DAL), currently approved in all forms of MS, might represent an answer to unmet needs in the symptomatic treatment of MS. Areas covered: The main pharmacological and clinical properties and safety issues of DAL, an extended-release formulation of 4-aminopyridine (4-AP), a broad-spectrum voltage-dependent potassium channel blocker, are described. Relevant publications were identified from a search of PubMed from 1966 to June 2014 (search terms 'dalfampridine OR fampridine OR 4-aminopyridine). DAL, 10 mg twice daily, improves walking ability in approximately one-third and walking speed in about 25% of patients, independently from disease course, compared with placebo; it also improves leg strength. Treatment is generally well tolerated, although there is a dose-dependent increased risk of seizures, especially with dosages > 10 mg twice daily. Expert opinion: DAL represents an option in the symptomatic treatment of MS. Improved ambulation can impact quality of life, motivation and adherence, enhancing the successful management of MS. It has still to be established whether this favorably impacts costs associated with MS.Expert Opinion on Drug Metabolism & Toxicology 12/2014; 11(2):1-12. DOI:10.1517/17425255.2015.993315 · 2.93 Impact Factor