Linard Filli1, Björn Zörner2, Sandra Kapitza2, Katja Reuter2, Lilla Lörincz2, David Weller2, Tabea Sutter2, Tim Killeen2, Philipp Gruber2, Jens A Petersen2, Michael Weller2, Michael Linnebank2. 1. From the Department of Neurology (L.F., B.Z., S.K. K.R., L.L., D.W., T.S., P.G., J.A.P., M.W., M.L.), University Hospital Zurich; Spinal Cord Injury Center (T.K.), Balgrist University Hospital, Zurich, Switzerland; and Department of Neurology (M.L.), Helios-Klinik Hagen-Ambrock, Hagen, Germany. linard.filli@usz.ch. 2. From the Department of Neurology (L.F., B.Z., S.K. K.R., L.L., D.W., T.S., P.G., J.A.P., M.W., M.L.), University Hospital Zurich; Spinal Cord Injury Center (T.K.), Balgrist University Hospital, Zurich, Switzerland; and Department of Neurology (M.L.), Helios-Klinik Hagen-Ambrock, Hagen, Germany.
Abstract
OBJECTIVE: To expand upon the limited knowledge of the long-term effects of prolonged-release (PR) fampridine in patients with multiple sclerosis (PwMS) regarding safety, walking improvements, and changes in drug responsiveness. METHODS: Fifty-three PwMS who completed the FAMPKIN core study were included in this extension trial. Drug efficacy was assessed in an open-label and randomized double-blind, placebo-controlled study design with regular baseline assessments over a period of 2 years using the Timed 25-Foot Walk (T25FW), 6-Minute Walk Test (6MWT), and 12-item MS Walking Scale (MSWS-12) as outcome measures. RESULTS: The data showed good tolerability and persisting efficacy of PR fampridine during long-term treatment in PwMS. Significant improvements in walking speed, endurance, and self-perceived ambulatory function were observed during open-label (T25FW: +11.5%; 6MWT: 10.7%; MSWS-12: 6.1 points) and double-blind controlled treatment with PR fampridine (T25FW: +13.1%; 6MWT: 11.9%; MSWS-12: 7.4 points). Several patients showed changes in drug responsiveness over time, resulting in an increased proportion of patients exceeding 10% or 20% improvements in walking measures after long-term treatment. CONCLUSIONS: Efficacy and tolerability data confirmed PR fampridine as a valuable long-term treatment for improving ambulatory function in gait-impaired PwMS. Similar results in open-label and double-blind phases reveal that the walking tests used are objective and reliable. The considerable proportion of patients in whom responsiveness to PR fampridine changed over time emphasizes the importance of regular reassessment of drug efficacy in clinical practice to optimize treatment. Such reassessments seem to be particularly important in patients with poor initial drug responses, as this group demonstrated enhanced responsiveness after long-term treatment. CLINICALTRIALSGOV IDENTIFIER: NCT01576354. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that PR fampridine significantly improved gait compared to placebo in a 2-week study in PwMS who had been using PR fampridine for 2 years.
OBJECTIVE: To expand upon the limited knowledge of the long-term effects of prolonged-release (PR) fampridine in patients with multiple sclerosis (PwMS) regarding safety, walking improvements, and changes in drug responsiveness. METHODS: Fifty-three PwMS who completed the FAMPKIN core study were included in this extension trial. Drug efficacy was assessed in an open-label and randomized double-blind, placebo-controlled study design with regular baseline assessments over a period of 2 years using the Timed 25-Foot Walk (T25FW), 6-Minute Walk Test (6MWT), and 12-item MS Walking Scale (MSWS-12) as outcome measures. RESULTS: The data showed good tolerability and persisting efficacy of PR fampridine during long-term treatment in PwMS. Significant improvements in walking speed, endurance, and self-perceived ambulatory function were observed during open-label (T25FW: +11.5%; 6MWT: 10.7%; MSWS-12: 6.1 points) and double-blind controlled treatment with PR fampridine (T25FW: +13.1%; 6MWT: 11.9%; MSWS-12: 7.4 points). Several patients showed changes in drug responsiveness over time, resulting in an increased proportion of patients exceeding 10% or 20% improvements in walking measures after long-term treatment. CONCLUSIONS: Efficacy and tolerability data confirmed PR fampridine as a valuable long-term treatment for improving ambulatory function in gait-impaired PwMS. Similar results in open-label and double-blind phases reveal that the walking tests used are objective and reliable. The considerable proportion of patients in whom responsiveness to PR fampridine changed over time emphasizes the importance of regular reassessment of drug efficacy in clinical practice to optimize treatment. Such reassessments seem to be particularly important in patients with poor initial drug responses, as this group demonstrated enhanced responsiveness after long-term treatment. CLINICALTRIALSGOV IDENTIFIER: NCT01576354. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that PR fampridine significantly improved gait compared to placebo in a 2-week study in PwMS who had been using PR fampridine for 2 years.
Authors: Sarah D Broicher; Linard Filli; Olivia Geisseler; Nicole Germann; Björn Zörner; P Brugger; M Linnebank Journal: J Neurol Date: 2018-02-20 Impact factor: 4.849
Authors: Tim Killeen; Christopher S Easthope; László Demkó; Linard Filli; Lilla Lőrincz; Michael Linnebank; Armin Curt; Björn Zörner; Marc Bolliger Journal: Sci Rep Date: 2017-05-15 Impact factor: 4.379
Authors: Linard Filli; Tabea Sutter; Christopher S Easthope; Tim Killeen; Christian Meyer; Katja Reuter; Lilla Lörincz; Marc Bolliger; Michael Weller; Armin Curt; Dominik Straumann; Michael Linnebank; Björn Zörner Journal: Sci Rep Date: 2018-03-21 Impact factor: 4.379
Authors: Núria Sola-Valls; Yolanda Blanco; María Sepúlveda; Sara Llufriu; Elena H Martínez-Lapiscina; Irati Zubizarreta; Irene Pulido-Valdeolivas; Carmen Montejo; Pablo Villoslada; Albert Saiz Journal: Ther Adv Neurol Disord Date: 2018-06-10 Impact factor: 6.570
Authors: Christian Meyer; Tim Killeen; Christopher S Easthope; Armin Curt; Marc Bolliger; Michael Linnebank; Björn Zörner; Linard Filli Journal: Sci Rep Date: 2019-03-26 Impact factor: 4.379
Authors: Philipp Albrecht; Ingrid Kristine Bjørnå; David Brassat; Rachel Farrell; Peter Feys; Jeremy Hobart; Raymond Hupperts; Michael Linnebank; Jožef Magdič; Celia Oreja-Guevara; Carlo Pozzilli; Antonio Vasco Salgado; Tjalf Ziemssen Journal: Ther Adv Neurol Disord Date: 2018-10-05 Impact factor: 6.570