A Potentially Effective New Antibody for Migraine Prevention

S. Andrew Josephson, MD


AccessMedicine from McGraw-Hill 

Migraine is a common disorder that accounts for a tremendous amount of disability worldwide. Strategies for treatment include acute abortive agents to stop attacks as well as preventative agents used to decrease the number and severity of attacks. Recently, a number of studies have demonstrated encouraging results for acute migraine treatment with antagonists of calcitonin gene-related peptide (CGRP), which is found throughout the brain regions responsible for migraine. Dodick and colleagues (2014) aimed to target this same molecule in a preventative strategy using a fully humanized monoclonal antibody against CGRP.

The authors conducted a randomized, double-blind, placebo-controlled phase 2 trial at 35 centers in the United States. Eligible patients age 18–65 had at least 1 year of migraine attacks and between 4 and 14 headache days per month. Patients with more headache days per month were supposed to be excluded, but an error allowed 4 of these patients into the trial. Patients had to discontinue all drug or other preventative treatments for 30 days prior to enrollment. Those patients who had previously failed to respond to adequate doses of two migraine preventative medications also were excluded.

Patients were randomized in a 1:1 fashion to either placebo or 150 mg of the active compound LY2951742, each injected subcutaneously every 2 weeks for 12 weeks. The primary endpoint assessed 12 weeks after completion of the 12-week treatment period was the mean change in the number of headache days over a 28-day period.

A total of 218 patients were randomized, and just fewer than 90% completed the study. The mean age of the patients was 41 years, 41% had aura at least once with their migraines, and 85% were women. The mean change from baseline was –4.2 days in the treatment group compared with –3.0 days in the placebo group (mean difference, –1.2 days; 90% confidence interval, –1.9 to –0.6; p = .003). Secondary outcomes all favored the treatment group, including a greater reduction in the number of migraine plus probable migraine days and the total number of attacks. A total of 49% of the treatment group were classified as 75% responders compared with 27% of the placebo group, and 32% of the treatment group achieved a complete response compared with 17% of the placebo group.

Adverse events were similar in the two groups, most commonly upper respiratory infections and viral infections. Two serious adverse events in the treatment group were a pregnancy and one case of peripheral vascular disease. There were four serious adverse events in the placebo group. Injection-site reactions occurred in 20% of the treatment group and 6% of the placebo group and mainly included injection-site pain or erythema.

This impressive study demonstrates promising results for a migraine preventative strategy using an antibody injection given every 2 weeks. Like many migraine trials, the placebo response rates were quite high; however, the fact that nearly one-third of patients in the treatment group achieved a complete response was remarkable. Further work is needed before this and other CGRP-related compounds are clinically available, but they remain a potentially important advance in both the acute and preventative treatment of migraine that could help millions of patients.