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Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration. Read More →

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In The Lancet Neurology, David Dodick and colleagues1 report an important study of treatment in migraine prophylaxis: parenteral administration of LY2951742, a monoclonal antibody to calcitonin gene-related peptide (CGRP). Mean decrease from baseline in migraine days in 4 weeks was higher in patients given LY2951742 (4·2) than in those given placebo (3·0; p=0·003).1 Results of other trials that use antibodies against CGRP will probably be published soon.Read More →

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In The Lancet Neurology, David Dodick and colleagues1 introduce monoclonal antibodies into the specialty of primary headache therapy. They report findings from a randomised, placebo-controlled, double-blind, phase 2 clinical trial of LY2951742, a neutralising humanised monoclonal antibody against calcitonin gene-related peptide (CGRP), for migraine prevention. The subcutaneous administration of LY2951742 once every 2 weeks reduced the mean number of migraine headache days per 28-day period between baseline and weeks 9–12 (primary endpoint; least-squares mean difference −1·2, 90% CI −1·9 to −0·6; p=0·0030) in a population with a high frequency of migraine; the antibody was also superior to placebo in several secondary endpoints after 12 weeks of treatment.Read More →

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These results provide preliminary evidence that LY2951742 might be beneficial in migraine prevention and provide support for the role of calcitonin gene-related peptide in the pathogenesis of migraine. Further controlled studies are needed to assess the safety and efficacy of monoclonal calcitonin gene-related peptide antibodies for the preventive treatment of migraine.Read More →