Effect of Atogepant for Preventive Migraine Treatment on Patient-Reported Outcomes in the Randomized, Double-blind, Phase 3 ADVANCE Trial
Richard B. Lipton, Patricia Pozo‐Rosich, Andrew Blumenfeld, Ye Li, Lawrence Severt, Jonathan Stokes, Lela Creutz, Pranav Gandhi, David W. Dodick
Abstract
<h3>Background and Objectives:</h3> The oral calcitonin gene-related peptide receptor antagonist atogepant is indicated for the preventive treatment of episodic migraine. We evaluated changes in patient-reported outcomes with atogepant in adults with migraine. <h3>Methods:</h3> In this phase 3, 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (ADVANCE), adults with 4-14 migraine days/month received atogepant 10, 30, or 60mg once daily, or placebo. Secondary endpoints included changes from baseline in Migraine-Specific Quality of Life Questionnaire (MSQ) v2.1 Role Function-Restrictive (RFR) domain at week 12 and mean monthly Activity Impairment in Migraine-Diary (AIM-D) Performance of Daily Activities (PDA) and Physical Impairment (PI) domains across the 12-week treatment period. Exploratory endpoints included change in MSQ- Role Function-Preventive (RFP) and Emotional Function (EF) domains; AIM-D Total scores; and Headache Impact Test-6 (HIT-6) change scores. <h3>Results:</h3> Of 910 participants randomized, 873 comprised the modified intent-to-treat population (atogepant 10mg [n=214]; 30mg [n=223]; 60mg [n=222]; placebo [n=214]). All atogepant groups demonstrated significantly greater improvements vs placebo in MSQ RFR that exceeded minimum clinically meaningful between-group difference (3.2 points) at week 12 (least-squares mean difference [LSMD] vs placebo: 10mg [9.9]; 30mg [10.1]; 60mg [10.8]; all <i>p</i><0.0001). LSMDs in monthly AIM-D PDA and PI scores across the 12-week treatment period improved significantly for atogepant 30 (PDA: −2.54; <i>p</i>=0.0003; PI: −1.99; <i>p</i>=0.0011) and 60mg (PDA: −3.32; <i>p</i><0.0001; PI: −2.46; <i>p</i><0.0001), but not 10mg (PDA: −1.19; <i>p</i>=0.086; PI: −1.08; <i>p</i>=0.074). In exploratory analyses, atogepant 30 and 60mg were associated with nominal improvements in MSQ RFP and EF domains, other AIM-D outcomes, and HIT-6 scores at the earliest timepoint (week 4) and throughout the 12-week treatment period. Results varied for atogepant 10mg. <h3>Discussion:</h3> Atogepant 30 and 60mg produced significant improvements in key patient-reported outcomes including MSQ-RFR scores and both AIM-D domains. Nominal improvements also occurred for other MSQ domains and HIT-6, reinforcing the beneficial effects of atogepant as a new treatment for migraine prevention. <h3>Trial Registration:</h3> ClinicalTrials.gov NCT03777059. Submitted: 12/13/2018; First patient enrolled: 12/14/2018. https://clinicaltrials.gov/ct2/show/NCT03777059 <h3>Classification of Evidence:</h3> This study provides Class II evidence that daily atogepant is associated with improvements in health-related quality of life measures in patients with 4-14 migraine days/month.