Erenumab in chronic migraine with medication overuse: Subgroup analysis of a randomized trial

Abstract

Objective: To determine the effect of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody, in patients with chronic migraine and medication overuse.

Methods: In this double-blind, placebo-controlled study, 667 adults with chronic migraine were randomized (3:2:2) to placebo or erenumab (70 or 140 mg), stratified by region and medication overuse status. Data from patients with baseline medication overuse at baseline were used to assess changes in monthly migraine days, acute migraine-specific medication treatment days, and proportion of patients achieving ≥50% reduction from baseline in monthly migraine days.

Results: Of 667 patients randomized, 41% (n = 274) met medication overuse criteria. In the medication overuse subgroup, erenumab 70 or 140 mg groups had greater reductions than the placebo group at month 3 in monthly migraine days (mean [95% confidence interval] -6.6 [-8.0 to -5.3] and -6.6 [-8.0 to -5.3] vs -3.5 [-4.6 to -2.4]) and acute migraine-specific medication treatment days (-5.4 [-6.5 to -4.4] and -4.9 [-6.0 to -3.8] vs -2.1 [-3.0 to -1.2]). In the placebo and 70 and 140 mg groups, ≥50% reductions in monthly migraine days were achieved by 18%, 36% (odds ratio [95% confidence interval] 2.67 [1.36-5.22]) and 35% (odds ratio 2.51 [1.28-4.94]). These clinical responses paralleled improvements in patient-reported outcomes with a consistent benefit of erenumab across multiple measures of impact, disability, and health-related quality of life. The observed treatment effects were similar in the non-medication overuse subgroup.

Conclusions: Erenumab reduced migraine frequency and acute migraine-specific medication treatment days in patients with chronic migraine and medication overuse, improving disability and quality of life.

Clinicaltrialsgov identifier: NCT02066415.

Classification of evidence: This study provides Class II evidence that erenumab reduces monthly migraine days at 3 months in patients with chronic migraine and medication overuse.

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Change from baseline in MMD over time

Least-squares mean (LSM) changes from baseline in monthly migraine days (MMD) in patients (A) without and (B) with medication overuse among patients with chronic migraine (CM) who were assigned to receive placebo, erenumab 70 mg, or erenumab 140 mg every month. Error bars represent 95% confidence intervals (CIs). *p < 0.005, **p < 0.001 for erenumab vs placebo. Proportion of patients (C) without and (D) with medication overuse who achieved ≥50% change from baseline in MMD among patients with CM who were assigned to receive placebo, erenumab 70 mg, or erenumab 140 mg every month.

Figure 2. Change from baseline in acute migraine-specific medication treatment days over time

Least-squares mean (LSM) changes from baseline in acute migraine-specific medication treatment days in patients (A) without and (B) with medication overuse among patients with chronic migraine who were assigned to receive placebo, erenumab 70 mg, or erenumab 140 mg every month. Error bars represent 95% confidence intervals (CIs). *p < 0.05, **p < 0.001 for erenumab vs placebo.

Figure 3. Proportion of patients with medication overuse at baseline who changed status to non–medication overuse at month 3, by acute medication category

Medication overuse defined as ≥15 days of simple analgesics (nonnarcotic analgesics such as acetaminophen or nonsteroidal anti-inflammatory drugs), ≥10 days of triptans, and ≥10 days of combination therapy (any combination of triptans, ergot derivatives, analgesics, or simple analgesics with opiates or butalbital) per month.