麻豆传媒

LONDON -- The only drug approved to improve mobility in multiple sclerosis (MS) patients -- dalfampridine (Ampyra) -- has long been plagued by doubts about its efficacy, but a randomized trial reported here suggests that the drug genuinely does produce clinically significant improvements in walking ability.

In the 633-patient, 24-week study, 43.2% of those receiving dalfampridine (known simply as fampridine outside the U.S.) showed improvement of at least 8 points on the 12-point, patient-reported MS Walking Scale (MSWS), compared with 33.6% of the placebo group (P=0.006), reported , of Plymouth University in England.

This translated to an odds ratio of 1.61 (95% CI 1.15-2.26) for achieving this result, which was the study's primary endpoint, Hobart told attendees at a late-breaking abstract session here at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.

Effects on some, though not all, objectively measured outcomes also significantly favored dalfampridine, he reported. These included the Timed Up-and-Go (43.4% vs 34.7% achieving greater than 15% improvement, P=0.03) and the Multiple Sclerosis Impact Scale's physical component (mean 8.0-point improvement versus 4.68 points for placebo, P<0.001).

No significant differences were seen in tests of balance or patient-reported hand function.

Hobart stressed the use of a patient-reported outcome "with an a priori threshold for clinical improvement" for the primary endpoint, which distinguishes the current trial from previous studies. Dalfampridine's registration trials used the timed 25-foot walk test as the primary outcome and lasted only 14 weeks. Patients showing any improvement after treatment versus baseline were classed as responders, and only a minority of patients achieved it.

Thus, the current trial serves to confirm a durable and clinically significant benefit for the drug, Hobart suggested.

, of the Cleveland Clinic, who was not involved with the trial, told 麻豆传媒 that he largely agreed with that assessment, and particularly with the use of a patient-reported outcome as the primary endpoint.

"We wonder if the improvement [seen] in short-term trials ... really continues over a longer period of time, and it seems that it does," he said. As for the use of MSWS as the primary outcome measure, Fox noted, "Patients want to walk better, and who else to better know if they're better than asking patients."

Patients in the multinational study, dubbed ENHANCE, had relatively advanced MS, with mean scores on the Expanded Disability Status Scale of about 5.5, and mean age of 49. About 60% were women. Half had relapsing-remitting MS while the other half showed a mix of progressive disease types. The mean MSWS score at baseline was about 64. Hobart noted that the choice of an 8-point improvement in this measure was made after discussion of what would represent a clinically noteworthy change in walking ability.

Treatment assignments were made 1:1 to either placebo or 10 mg dalfampridine twice daily.

The time course of mean MSWS scores during the trial reflected the drug's rapid onset of action as well as its equally rapid washout when stopped. Two weeks into the study, Hobart reported, patients in the active drug group showed a clear improvement relative to the placebo group (mean improvement of approximately 7 points versus 2.5). At a final evaluation at week 26, 2 weeks after stopping the drug, both groups had mean MSWS scores close to baseline values.

In a more stringent responder analysis, Hobart said about 38% of dalfampridine patients achieved 10-point improvements at week 24, compared with 27% of the placebo group (P not reported).

Scores for the Timed Up-and-Go test showed a similar pattern, although the maximal improvement was seen at week 20 followed by a marked drop-off by week 24, seen in both treatment groups.

Adverse events, both serious and non-serious, were seen at similar rates in both groups. Hobart said no new safety signals were seen in the trial.

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