Friday, 10 February 2017

#ClinicSpeak & #ResearchSpeak: is long-term fampridine good or bad?

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.

CoI: multiple

7 comments:

  1. Good drug, but coming off it suspecting it is the cause of recurrent UTI, tough getting my baseline back.

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  2. "Presumably as MS worsens new axons may become responsive."

    Is this saying "new" as in there are more damaged axons so there
    is more opportunity for the drug to respond.

    ReplyDelete
  3. Some people state that they are noticeably worse if they miss a few tablets. If this is the case then it would not be a neuroprotective or remyelination agent. It is more likely to increase the intensity of the signals that are sent by the brain to the limbs.

    ReplyDelete
  4. Post deleted as requested. If you want to repost without names please do.
    When you delete the post it removes the replies too

    ReplyDelete
  5. I was on compounded slow release 4 amino pyridine (the active ingredient of Fampridine/Fampyra) for 2 years.

    I am SPMS and EDSS 8.5. I live at home in Australia with my wife who is my carer.

    Early in my treatment my neurologist suggested assessing the efficacy by ceasing 4AP for a week. At that stage I was EDSS 8 and I tended towards 9. I resumed at the end of the week and reverted to 8.

    The acknowledged side effect of 4AP is a lowering of the seizure threshold and 4 months ago I had my, first ever, tonic seizure. I ceased this medication and the difference in my EDSS is not noticeable.

    I'd be interested to hear an informed analysis.

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  6. I'm now at year three of the compounded version of ampyridine (slow release). Prof G's uncertainty about this drug spooked me before and again now. I definitely know if I dip a dose. Must look at the literature from the Canadian studies where the non slow release drug was taken for some time. Maybe contact your Aussie mates re trial, there a lot people out here who are accessing the compound version.

    ReplyDelete
    Replies
    1. I was told that the slow release was critical to managing the seizure risk.

      4AP was originally a heart medication and it was repurposed as Famprdine/Fampyra after the 25ft walk phase 3 trials. Those trials, I believe, did not assess long periods of dosage.

      Delete

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