Assessing dalfampridine efficacy in the physicians office

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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