Treatment with the anti-calcitonin gene-related peptide (CGRP) drug erenumab resulted in a significantly reduction in the number of monthly migraine days for patients with chronic migraine, according to the results of a phase II study published in Lancet Neurology.1 Similar reductions were seen for patients assigned to either the 70-mg or the 140-mg dose.
“Because of its favorable safety, tolerability, and efficacy profile in this study, and its once-monthly administration, subcutaneous erenumab has the potential to increase real-world adherence to treatment in patients with chronic migraine,” wrote Stewart Tepper, MD, Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues. “This could address an important unmet need, because just 17–20% of patients with chronic migraine adhere to migraine preventive drugs after 1 year, and non-adherence can lead to worsening of the disorder.”
For several decades, studies have suggested a role for CGRP in migraine, and that targeting the CGRP pathway might help to prevent migraine. Tepper and colleagues conducted this study to determine if erenumab, a fully human monoclonal antibody against CGRP, could prevent migraine in patients with chronic migraine.
The study included patients aged 18 to 65 with chronic migraine, defined at 15 or more headache days per month of which eight or more were migraine days.
Patients were randomly assigned 3:2:2 to subcutaneous placebo (n=286), erenumab 70 mg (n=191), or erenumab 140 mg (n=190) every 4 weeks for 12 weeks. The primary endpoint was change in monthly migraine days from baseline to the last 4 weeks of the double-blind treatment.
At study initiation, patients had mean monthly migraine days of 18.2, 17.9, and 17.8 for the placebo, 70-mg, and 140-mg groups, respectively. Treatment with either dose of erenumab resulted in a 2.5-day greater reduction in monthly migraine days compared with placebo (average reduction of -6.6 vs. -4.2 days; P<0.0001).
“Reductions of headache frequency from baseline of more than 30% and by more than one day per month are generally thought to represent a clinically relevant change,” the researchers wrote. “The reductions in monthly migraine days in this study represent a change of more than 30%, and more than one day per month relative to patients receiving placebo.”
Of the 667 patients who underwent treatment, 637 completed therapy. Four patients withdrew because of adverse events (two in the placebo group and two in the 140-mg group). A similar percentage of patients in the placebo (39%), erenumab 70 mg (44%), and erenumab 140 mg (47%) groups reported adverse events. The most frequently reported events were injection-site pain, upper respiratory tract infection, and nausea. No serious adverse events resulted in treatment discontinuation.
In an editorial that accompanied the study, Maria Adele Giamberardino and Raffaele Costantini, of G D'Annunzio University of Chieti, Italy, wrote that erenumab may be a “promising new therapy for prevention of this highly problematic type of chronic pain.”2
They added that selection criteria for patients in the study were strict and excluded patients with most medical comorbidities.
“Future studies should verify whether similar efficacy is maintained with erenumab in the general chronic migraine population, including patients with comorbidities, and whether interference or interactions occur in patients undergoing multiple treatments, especially those with increased risks such as for cardiovascular events, as in the case of concurrent hypertension,” they wrote.
1. Tepper S, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. Epub 2017 Apr 28.
2. Giamberardino MA, et al. Challenging chronic migraine: targeting the CGRP receptor. Lancet Neurol. Epub 2017 Apr 28.