Treatment with erenumab reduces the number of migraine days in individuals for whom multiple conventional oral migraine treatments have failed, according to the results of a new phase III clinical trial published in The Lancet. The LIBERTY trial shows that therapy directed against the calcitonin gene-related peptide (CGRP) receptor could provide a well-tolerated and effective treatment option for an underserved population of patients with episodic migraine who do not respond to other therapies.

Conventional treatment of migraine consists of therapies that were not developed specifically for the condition. However, the efficacy and tolerability of these agents is poor. “About 75% of patients with migraine stop preventive migraine therapy within 6 months due to adverse effects or lack of efficacy,” explains the lead author of the LIBERTY trial, Uwe Reuter. “These patients are considered difficult-to-treat due to a high level of frustration based on prior treatment failures. Often these individuals also suffer from comorbidities such as depression and anxiety.”

In the past few years, new migraine-specific therapies have emerged. Several agents that target CGRP, a molecule upregulated during migraine attacks, have been found to be safe and effective in clinical trials. Erenumab, an antibody that targets the CGRP receptor, became the first of these disease-specific therapies to be approved for treatment of migraine in 2018.

In LIBERTY — a 12-week, double-blind, randomized, placebo-controlled trial — Reuter and colleagues investigated whether erenumab treatment might be an effective option in patients with difficult-to-treat episodic migraine whose condition previously failed to respond to between two and four other therapies. The team randomly assigned 246 individuals to receive either subcutaneous injection of erenumab or placebo once every 4 weeks for 12 weeks.

After 12 weeks, 30% of participants who received erenumab achieved the primary end point of a 50% or greater reduction in the number of monthly migraine days from baseline, compared with only 14% of those who received placebo.

As demonstrated by previous large clinical trials, erenumab was well tolerated and the frequency of adverse events seen with erenumab treatment was similar to that seen with placebo. More than 98% of participants completed 3 months of treatment with erenumab, whereas in trials of topiramate, an antiseizure medication also used to prevent migraine, ~25% of patients with migraine drop out by the same time point owing to adverse events.

erenumab reduces the number of migraine days in individuals for whom multiple conventional oral migraine treatments have failed

“This patient group has never been studied before in a migraine prevention trial,” remarks Reuter. As such, this study provides the first evidence that erenumab is an effective preventive treatment in individuals with episodic migraine who previously did not respond to multiple other treatments. Further investigation is now needed to examine the long-term adherence of these patients to erenumab beyond 12 weeks.