Sustained-released fampridine in multiple sclerosis: effects on gait parameters, arm function, fatigue, and quality of life

AbstractSustained-release fampridine (fampridine-SR) improves gait velocity and self-perceived capacities in people with multiple sclerosis (MS). However, little is known about the treatment’s effect on temporospatial gait parameters, walking endurance, general fatigue, hand function and quality of life (QoL). We therefore sought to evaluate these parameters in a real-world setting: 120 consecutive, eligible patients with MS were evaluated at baseline (D0) and after two weeks (D14) of fampridine-SR. Lastly, D14 responders were again evaluated after three months (M3). Response to treatment was defined as a 15 % improvement in at least one of the following tests: the Timed 25-Foot-Walk (T25FW), the 2-min walk test (2MWT) and the Multiple Sclerosis Walking Scale (MSWS-12). Eighty-three patients (74 %) were found to be responders. The response rate was lower when assessed as a 20 % improvement in the T25FW (50.9 %), and this difference was particularly marked for fast-walking subjects (i.e. T25FW <8 s at baseline). Responders displayed mean improvements (at D14 and M3, respectively) of 34.5 and 35.5 % in the T25FW, 39 and 36.7 % in the 2MWT and 19 and 11.6 % in the MSWS-12. The increase in gait velocity was due to both a higher cadence and a greater step length. Responders showed also significant, lasting reductions in fatigue (visual analogue scale and the Fatigue Severity Scale; p < 10−4 at D14 and <0.01 at M3) and significant, lasting improvements in hand function (9 Hole Peg Test; p < 0.05) and QoL (SF-12; p < 0.01). In conclusion, several MS-induced symptoms other than gait velocity may be improved by fampridine-SR, even if this remains to be more specifically evaluated in future studies.

[1]  P. Feys,et al.  Comparison of the 2- and 6-minute walk test in multiple sclerosis , 2011, Multiple sclerosis.

[2]  N. Larocca,et al.  Application to Patients With Multiple Sclerosis and Systemic Lupus Erythematosus , 2016 .

[3]  A. Vincent,et al.  Sustained-Release Fampridine (4-Aminopyridine) in Multiple Sclerosis: Efficacy and Impact on Motor Function , 2013, Drugs in R&D.

[4]  Alessandra Solari,et al.  The multiple sclerosis functional composite: different practice effects in the three test components , 2005, Journal of the Neurological Sciences.

[5]  A. Achiron,et al.  Gait analysis in multiple sclerosis: characterization of temporal-spatial parameters using GAITRite functional ambulation system. , 2009, Gait & posture.

[6]  A. Cross,et al.  Fampridine-SR in multiple sclerosis: a randomized, double-blind, placebo-controlled, dose-ranging study , 2007, Multiple sclerosis.

[7]  L. Krupp,et al.  Dose comparison trial of sustained-release fampridine in multiple sclerosis , 2008, Neurology.

[8]  Ilse Lamers,et al.  Perceived and actual arm performance in multiple sclerosis: relationship with clinical tests according to hand dominance , 2013, Multiple sclerosis.

[9]  A. Compston,et al.  Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis , 2001, Annals of neurology.

[10]  G. Moonen,et al.  Motor Fatigue Measurement by Distance-Induced Slow Down of Walking Speed in Multiple Sclerosis , 2012, PloS one.

[11]  J. Ware,et al.  A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. , 1996, Medical care.

[12]  T. Berger,et al.  Assessing the long-term clinical benefit of prolonged-release fampridine tablets in a real-world setting: a review of 67 cases , 2013, Patient related outcome measures.

[13]  Diana M Sobieraj,et al.  Minimally important clinical difference of the Timed 25-Foot Walk Test: results from a randomized controlled trial in patients with multiple sclerosis , 2012, Current medical research and opinion.

[14]  H. Wiendl,et al.  Long-term effects of dalfampridine in patients with multiple sclerosis , 2014, Journal of the Neurological Sciences.

[15]  F. Bethoux,et al.  Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials , 2015, Multiple sclerosis.

[16]  R. Kaji,et al.  Effects of 4‐aminopyridine in experimental CNS demyelination , 1988, Neurology.

[17]  Deborah M. Miller,et al.  Quality of Life in Multiple Sclerosis: Determinants, Measurement, and Use in Clinical Practice , 2010, Current neurology and neuroscience reports.

[18]  S. Reingold,et al.  The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment , 1999, Multiple sclerosis.

[19]  L. Krupp,et al.  Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial , 2009, The Lancet.

[20]  N. Larocca,et al.  The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. , 1989, Archives of neurology.

[21]  A J Thompson,et al.  Measuring the impact of MS on walking ability , 2003, Neurology.

[22]  L. Krupp,et al.  Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease. , 2006, Multiple sclerosis.

[23]  S. Bowman,et al.  The assessment of fatigue in primary Sjögren's syndrome , 2003, Scandinavian journal of rheumatology.

[24]  G Giovannoni,et al.  Multiple sclerosis related fatigue , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[25]  U. Dalgas,et al.  Changes in cognition, arm function and lower body function after Slow-Release Fampridine treatment , 2014, Multiple sclerosis.

[26]  D. Goodkin,et al.  Upper extremity function in multiple sclerosis: improving assessment sensitivity with box-and-block and nine-hole peg tests. , 1988, Archives of physical medicine and rehabilitation.

[27]  J. Fischer,et al.  Use of the multiple sclerosis functional composite as an outcome measure in a phase 3 clinical trial. , 2001, Archives of neurology.

[28]  George C. Ebers,et al.  The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability , 2010, Brain : a journal of neurology.

[29]  L. Krupp,et al.  A phase 3 trial of extended release oral dalfampridine in multiple sclerosis , 2010, Annals of neurology.