BACKGROUND AND OBJECTIVES: Three phase 3 trials demonstrated the efficacy and safety of atogepant in episodic migraine (EM) and chronic migraine (CM) across 12-week treatment periods. This analysis evaluates improvements in efficacy and functional outcomes in the first 4 weeks of treatment with the oral calcitonin gene-related peptide receptor antagonist, atogepant, for the preventive treatment of migraine.
METHODS: ADVANCE, ELEVATE, and PROGRESS were phase 3, multicenter, randomized, double-blind, placebo-controlled 12-week trials. ADVANCE and ELEVATE included participants aged 18-80 years with >1 year history of EM and 4-14 monthly migraine days (MMDs). ELEVATE required previous treatment failures to 2-4 classes of oral preventives. PROGRESS included participants aged 18-80 years with >1 year history of CM, =15 monthly headache days, and =8 MMDs. This analysis reports the atogepant 60 mg once daily (QD) and placebo treatment arms. Outcomes included efficacy endpoints (reporting a migraine day on day 1, change from baseline in weekly migraine days [WMDs] at weeks 1-4, and in MMDs in the first 4 weeks) and functional endpoints evaluated by the Activity Impairment in Migraine-Diary (AIM-D) at weeks 1-4 and the European Quality-of-Life 5-Dimension 5-Level (EQ-5D-5L) at weeks 1-2 and 4.
RESULTS: The modified intent-to-treat population included the ADVANCE (atogepant, n = 222; placebo, n = 214), ELEVATE (atogepant, n = 151; placebo, n = 154), and PROGRESS (atogepant, n = 256; placebo, n = 246) studies. Atogepant-treated participants had greater reductions in the proportion of participants with a migraine day on day 1. The odds ratio compared with placebo was 0.39 (95% CI 0.23-0.67; p = 0.0006) in ADVANCE, 0.53 (95% CI 0.29-0.94, p = 0.031) in ELEVATE, and 0.63 (95% CI 0.43-0.93, p = 0.021) in PROGRESS. Atogepant treatment reduced WMDs at weeks 1-4 and MMDs in the first 4 weeks, and improved AIM-D and EQ-5D-5L at all assessed timepoints for weeks 1-4 compared with placebo.
DISCUSSIONS: Atogepant 60 mg QD demonstrated superiority to placebo in efficacy and functional measures in the first 4 weeks of treatment across 3 preventive studies, 2 in EM and 1 in CM.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03777059; NCT04740827; NCT03855137. Submitted: 12/13/2018; 02/02/2021; 02/25/2019. First patient enrolled: 12/14/2018; 03/05/2021; 03/11/2019 clinicaltrials.gov/ct2/show/NCT03777059. clinicaltrials.gov/ct2/show/NCT04740827 clinicaltrials.gov/ct2/show/NCT03855137.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that atogepant 60 mg QD reduces migraine frequency and improves functional outcomes within 4 weeks of initiation in patients with EM and patients with CM.
| Discipline Area | Score |
|---|---|
| Physician |  |
Physician rater
How does it compare with other treatments for migraine?
Physician rater
The observation that the improvement in migraine prophylaxis occurs early in the 12-week RCTs of atogepant is not that important. Clinicians already have a feeling for this.
Physician rater
Another medication for the armamentarium of migraine prophylaxis. Pregnancy data are essential and cost limitations are important. Direct comparison with botulinum toxin and CGRP monoclonals may allow value assessment.
Physician rater
This article combines several recent studies of the oral CGRP receptor antagonist atogepant and emphasizes the drug's early beneficial effects when taken daily for prevention among patients with episodic and chronic migraine. The utility of this article will be higher for those not familiar with the primary results previously published from the three included studies.
Physician rater
Having three RCTs in this study provides more support for the claim that stogepant is beneficial for migraine treatment. The one downside of this article is that, a majority of the population in all three studies were White females. Many clinicians work with patients who do not fall into that patient demographic.
, McMaster University