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

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 healthrelated 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.