“Erenumab might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options,” MDLinx reports that Dr Uwe Reuter of Charite Universitaetsmedizin Berlin in Germany and colleagues conclude.
Current preventive treatments used for episodic migraine, including beta-blockers, topiramate, valproate, and amitriptyline, have poor efficacy and tolerability, the authors note. “As a result, many patients’ conditions cannot be managed with available preventives, and patients experience high disability and severely impaired quality of life.”
Erenumab targets calcitonin gene-related peptide (CGRP), which appears to play a role in migraine. In the LIBERTY trial, a multisite phase 3b study in patients with episodic migraine, the authors randomly assigned 246 patients to erenumab 140 mg or placebo injections subcutaneously every 4 weeks for 12 weeks. Patients had failed two (39%), three (38%), or four (23%) previous treatments.
The study found that 30% of patients in the erenumab group had a 50% or higher reduction in mean monthly migraine days, vs 14% of those on placebo (odds ratio, 2.7), a significant difference – 6% of patients in both groups had injection site pain, which was the most common treatment-emergent adverse effect.
“So far, few data are available to guide evidence-based treatment decisions in patients in whom previous treatments have been unsuccessful,” Reuter and colleagues write. “Our study provides the first direct, controlled trial evidence for a novel CGRP-directed therapy, which will allow practitioners to consider the place of these novel therapies in evidence-based treatment algorithms.”
Dr Andrew Charles of the UCLA Goldberg Migraine Programme at the David Geffen School of Medicine at the University of California – Los Angeles, wrote a comment accompanying the study.
“The development of migraine-specific preventive therapies based upon solid clinical science implicating CGRP as a primary mediator of migraine holds the promise of improved efficacy and tolerability compared with treatments that were initially developed for other conditions,” he writes.
“Reuter and colleagues’ study not only supports the results of previous clinical trials showing that monoclonal antibodies targeting CGRP are generally efficacious, but also shows that erenumab is efficacious specifically in the difficult-to-manage subset of patients who have previously unsuccessfully tried between two and four previous migraine preventive treatments,” he adds.
The report says Novartis Pharma, which makes erenumab, funded the study.
Background: A substantial proportion of patients with migraine does not respond to, or cannot tolerate, oral preventive treatments. Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine. We assessed its efficacy and tolerability in patients with episodic migraine in whom previous treatment with two-to-four migraine preventives had been unsuccessful.
Methods: LIBERTY was a 12-week, double-blind, placebo-controlled randomised study at 59 sites in 16 countries. Eligible patients were aged 18–65 years and had a history of episodic migraine with or without aura for at least 12 months, had migraine for an average of 4–14 days per month during the 3 months before screening, and had been treated unsuccessfully (in terms of either efficacy or tolerability, or both) with between two and four preventive treatments. Eligible participants were randomly assigned (1:1) to receive either erenumab 140 mg (via two 70 mg injections) or placebo every 4 weeks subcutaneously for 12 weeks. Randomisation was by interactive response technology and was stratified by monthly frequency of migraine headache (4–7 vs 8–14 migraine days per month) during the baseline phase. Cenduit generated the randomisation list and assigned participants to groups. Participants, investigators, people doing various assessments, and the study sponsor were masked to treatment assignment. The primary endpoint was the proportion of patients achieving a 50% or greater reduction in the mean number of monthly migraine days during weeks 9–12. Efficacy was measured in the full analysis set, which included all randomly assigned patients who started their assigned treatment and completed at least one post-baseline monthly migraine day measurement. Safety and tolerability were assessed by recording adverse events and by physical examination, assessment of vital signs, clinical laboratory assessments, and electrocardiography. Safety was assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT03096834. The trial is closed to new participants, but the open-label extension phase is ongoing.
Findings: Between March 20, 2017, and Oct 27, 2017, 246 participants were randomly assigned, 121 to the erenumab group and 125 to the placebo group. 95 of 246 (39%) participants had previously unsuccessfully tried two preventive drugs, 93 (38%) had tried three, and 56 (23%) had tried four. At week 12, 36 (30%) patients in the erenumab had a 50% or greater reduction from baseline in the mean number of monthly migraine days, compared with 17 (14%) in the placebo group (odds ratio 2·7 [95% CI 1·4–5·2]; p=0·002). The tolerability and safety profiles of erenumab and placebo were similar. The most frequent treatment-emergent adverse event was injection site pain, which occurred in seven (6%) participants in both groups.
Interpretation: Compared with placebo, erenumab was efficacious in patients with episodic migraine who previously did not respond to or tolerate between two and four previous migraine preventive treatments. Erenumab might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options.
Uwe Reuter, Peter J Goadsby, Michel Lanteri-Minet, Shihua Wen, Peggy Hours-Zesiger, Michel D Ferrari, Jan Klatt
The Lancet article summary[/link