Neurology Practice Changers 2014

Bret S. Stetka, MD; Andrew N. Wilner, MD


December 08, 2014

In This Article

Novel Approaches to Migraine Prophylaxis

2014 saw the first FDA approval of a transcutaneous battery-powered neurostimulator known as Cefaly® (STX-Med; Herstal, Liège, Belgium) for the prophylactic treatment of migraine. Cefaly follows the FDA approval in 2013 of Cerena (eNeura Therapeutics; Sunnyvale, California), a transcranial magnetic stimulator for the acute treatment of pain in migraine with aura.

Cefaly, a transcutaneous supraorbital nerve stimulator, proved efficacious in a double-blind, randomized, controlled trial of 67 patients at five Belgian headache clinics (PREMICE trial).[31] The active therapy group (34 participants) received neurostimulation with a pulse width of 250 μs, frequency of 60 Hz, and maximum intensity of 16 mA. The sham therapy group (33 participants) received neurostimulation with a pulse width of 30 μs, frequency of 1 Hz, and maximum intensity of 1 mA. Daily treatments lasted 20 minutes.

Active stimulation was superior to sham stimulation on numerous endpoints, including percentage of responders (≥ 50% reduction in number of migraine days between the run-in period and third month), number of migraine attacks, number of headache days, and number of required antimigraine drugs. The number of migraine days between the run-in period and third month was reduced in the active group more than the sham group, but the difference between the groups fell short of statistical significance (P = .054). Other than a tingling or massaging sensation where the device stimulated the forehead, there were no adverse effects.

Cefaly is indicated as an alternative to drug therapy for migraine prevention. If necessary, Cefaly could potentially be combined with prophylactic drug treatments, although such trials have not been reported. In a European uncontrolled postmarketing study, 54.4% of the 2313 participants who rented the Cefaly device were "satisfied" and decided to buy it.[32]

Another novel treatment approach to the prophylaxis of migraine attacks is ALD403, an antibody to calcitonin gene-related peptide (CGRP).[33] CGRP has been implicated in the pathophysiology of migraine, because CGRP infusions can produce a migraine-like attack. CGRP receptor antagonists are also effective for migraine treatment, although none are FDA-approved.

In this randomized, double-blind, placebo-controlled, phase 2 trial, patients with 5-14 migraine days out of 28 days received either ALD403 1000 mg intravenously (n = 81) or placebo (n = 82) to assess safety and effectiveness as migraine prophylaxis. Patients in the active treatment arm received a single infusion with a half-life of 31 days.

At weeks 5-8, the ALD403-treated patients had a decrease in migraine days of -5.6 vs -4.6 for the placebo group (difference, -1.0 migraine day; P = .0306). In addition, 11 patients had no migraine attacks—all of whom were in the ALD403 group. There were no infusion reactions. Adverse events were common in both the treatment and placebo groups, but these were mild to moderate and transient.

These positive results warrant a phase 3 investigation to determine whether this new approach of using a monoclonal antibody to CGRP provides effective migraine prophylaxis. A single infusion lasting 1 month or more could prove more attractive than daily medication prophylaxis for many patients with recurrent migraine.


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