Fampridine non-responders may become responders; there is a need to reassess. #BartsMS #ClinicSpeak #ResearchSpeak
The other day a patient asked me 'If I didn't respond to Fampridine (slow-release 4-aminopyridine) last year will I be able to try again to see if I respond now?'. As we don't have much experience with Fampridine, apart from a few patients paying for it privately and our trial cohort, I asked a colleague who said 'yes'; he had seen non-responders become responders a year or so later. Presumably as MS worsens new axons may become responsive. It is reassuring to see below that some pwMS see improvements in responsive over time. The conclusion of the authors' sums it up: 'The considerable proportion of patients in whom responsiveness to PR fampridine changed over time emphasises the importance of regular reassessment of drug efficacy in clinical practice to optimise 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'.
The question that I still have is how does fampridine really work; some argue it may be neuroprotective and others, including myself, still worry that it may hasten axonal loss by the 'whipping a dead-horse' analogy. Some of the surviving axons may be overworked by fampridine, which may increase their chances of degenerating. If you don't know the answer then it is time to do a study. Who has patients and the time to do a pre- and post-fampridine CSF study of neurofilament light (NFL) levels. If fampridine causes the CSF NFL levels to drop significantly it is neuroprotective. If on the other hand fampridine causes the NFL levels to rise then it is hastening neurodegeneration. If there are any groups out there who want to do the study we can collaborate with you by doing the lab work and we could help you with power calculations for the study.
Filli et al. Monitoring long-term efficacy of fampridine in gait-impaired patients with multiple sclerosis. Neurology. 2017 Feb 1. pii: 10.1212/WNL.0000000000003656. doi: 10.1212/WNL.0000000000003656.
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.
Labels: #ClinicSpeak, #ResearchSpeak, fampridine