Dalfampridine (extended release 4-aminopyridine) has shown in three
recent randomised controlled trials (RCT) to improve walking speed in
people with MS. The first phase II RCT had the percent change in walking
speed as the primary efficacy variable.
Results did not show statistical significance and instead a responder
was defined as anyone whose walking speed for at least three of four
visits during the treatment period was faster than the maximum speed
measured in the five non-treatment visits and this reached statistical
significance. Therefore this definition of a responder, was based
entirely upon consistency rather than magnitude of response and was used
in both subsequent phase III RCTs.
These phase III trials showed more ‘consistent responders’ in the
dalfampridine groups, which formed the basis of the FDA approval. The
dalfampridine group had on average a 25.5% improvement in walking speed,
versus 4.2% improvement in the placebo group. Unfortunately the
‘consistent responder’ criterion cannot feasibly be used in the
physician’s office. Instead the reviewers in this article outline that
catergorising responders based upon their magnitude of response, by
measuring repeated pre-and post-dalfampridine Timed 25-Foot Walks
(T25FW), is the most practical for clinicians.
As stated by the European Medicines Agency ‘Patients should be
evaluated after two weeks and treatment should be stopped for those who
have not shown an improvement’. This then raises the question of what
cut-off of T25FW improvement should support a clinician’s decision to
continue dalfampridine. Overall, this review feels a cut-off of 20-30%
seems most appropriate but this should be used in conjunction with
clinical acumen, as 4-aminopyridine may benefit people with MS in ways
beyond that of walking speed.
Authors: Raffel J, Malik O
Source: Mult Scler. 2013 May 31. [Epub ahead of print]
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