Prolonged-release fampridine in multiple sclerosis: Improved ambulation effected by changes in walking pattern

Abstract

BACKGROUND Prolonged-release fampridine (PR-fampridine, 4-aminopyridine) increases walking speed in the timed 25-foot walk test (T25FW) in some patients (timed-walk responders) with multiple sclerosis (MS). OBJECTIVE To explore the effects of PR-fampridine on different aspects of walking function and to identify associated gait modifications in subjects with MS. METHODS In this prospective, randomized, placebo-controlled, double-blind, phase II study (FAMPKIN; clinicaltrials.gov, NCT01576354), subjects received a 6-week course of oral placebo or PR-fampridine treatment (10 mg, twice daily) before crossing over. Using 3D-motion-analysis, kinematic and kinetic parameters were assessed during treadmill walking (primary endpoint). Clinical outcome measures included T25FW, 6-minute walk test (6MWT), and balance scales. Physical activity in everyday life was measured with an accelerometer device. RESULTS Data from 55 patients were suitable for analysis. Seventeen subjects were timed-walk responders under PR-fampridine. For the total study population and for responders, a significant increase in walking speed (T25FW) and distance (6MWT) was observed. Gait pattern changes were found at the single-subject level and correlated with improvements in the T25FW and 6MWT. Physical activity was increased in responders. CONCLUSION PR-fampridine improves walking speed, endurance, and everyday physical activity in a subset of subjects with MS and leads to individual modifications of the gait pattern.

Monitoring long-term efficacy of fampridine in gait-impaired patients with multiple sclerosis

“…In particular, those patients who showed a moderate to poor response in terms of walking improvement under PR fampridine at initial assessment were likely to improve their responsiveness to the drug over time, thus highlighting the necessity to regularly reassess the efficacy of PR fampridine on ambulatory function in PwMS. Persisting drug efficacy, combined with the fact that PR fampridine has also demonstrated beneficial effects in chronic progressive MS, 14,16 where alternative treatment options to improve walking function are virtually absent, confirm PR fampridine as an important option in symptomatic, long-term treatment for gait-impaired PwMS.…”

“…6,7 Prolonged-release (PR) fampridine blocks voltage-gated potassium channels, thereby improving signal conduction in demyelinated nerve fibers. 8,9 Whereas beneficial effects of short-term treatment with PR fampridine on maximal walking speed [10][11][12][13][14] and additional functional outcomes 7,[13][14][15] (e.g., walking endurance) are wellcharacterized in PwMS, little information exists regarding the long-term safety and efficacy of therapy with PR fampridine. Open-label treatment over periods of 1 and 3 years demonstrated good tolerability and persisting improvement in ambulatory function 16 and fatigue.…”

Multiple Sclerosis and Clinical Gait Analysis before and after Fampridine: A Systematic Review

“…The MSFC battery of tests also includes tests to evaluate upper-limb function (the 9 Hole-Peg Test) and cognition (the Paced Auditory Serial Addition Test). Secondary Criteria Other walking tests, such as the 2-Minute Walk Test (2MWT) [19,23,25,27] or the 6-Minute Walk Test (6MWT), were sometimes used in association with the T25FW to evaluate endurance [16,20,28,29]. The most recent studies [17,18,28] also used the 6-Spot Step Test to evaluate coordination and balance while walking.…”

“…Spasticity and muscle strength in the lower limbs were evaluated using the Ashworth scale and the Lower Extremity Manual Muscle Strength test, respectively [8,9,25,29].…”

“…With a cut-off of 28 days, 5 studies were classified as short term [16-18, 20, 23] and 13 as long term [8,9,14,15,19,21,22,24,25,[27][28][29][30]. The mean follow-up duration of short-term studies was 2.4 weeks and was 16 weeks for long-term studies.…”