Atogepant for Chronic Migraine May Reduce Medication Overuse-Related Headache

Atogepant for chronic migraine effectively reduces mean monthly migraine days (MMDs) among patients with acute medication overuse, according to the findings of a study published in Neurology.

Atogepant is a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist designed to prevent migraine.

The PROGRESS study was a multicenter, phase 3, randomized, double-blind, placebo-controlled, parallel-group, trial conducted between 2019 and 2022 at 142 sites globally. Patients (N=755; mean age, 42.1; women, 87.6%; body mass index [BMI], 25.5 kg/m²) with chronic migraine were randomly assigned in a 1:1:1 ratio to receive 30 mg atogepant twice daily (n=253), 60 mg atogepant once daily (n=256), or placebo (n=246) for 12 weeks.

The primary outcome was the change in MMDs from baseline throughout the 12-week treatment period. In this subgroup analysis, outcomes were compared between patients with (66.2%) and without acute medication overuse, defined as the use of simple analgesics 15 days or more per month or triptans, ergots, or combinatorial therapies 10 days or more per month.

Among the study population, acute medication use ranged from 14.5 to 15.5 days per month.

Stratified by medication overuse, those with overuse at baseline had mean MMDs of 19.0 to 19.7 days and those without overuse, 17.8 to 18.4 days.

Compared with placebo, the least-squares mean difference (LSMD) in MMDs was reduced by 2.7 days with atogepant twice a day and by 1.9 days with atogepant once a day among those with overuse and by 1.7 days and 1.6 days for those without overuse, respectively.

The proportion of patients who achieved a 50% or more reduction in mean MMDs across the 3-month treatment period was 44.7% and 39.1% for the atogepant twice a day, 41.8% and 39.5% for the atogepant once a day, and 24.9% and 28.6% for the placebo cohorts among patients with and without overuse, respectively.

Atogepant once (odds ratio [OR], 2.5; 95% CI, 1.5-4.0) or twice (OR, 2.3; 95% CI, 1.4-3.7) a day was associated with higher odds of achieving a 50% reduction or more in mean MMDs from baseline compared with placebo among the subset of patients with medication overuse. Conversely, atogepant once (OR, 1.7; 95% CI, 0.8-3.2) or twice (OR, 1.7; 95% CI, 0.8-3.3) a day was not associated with a 50% or greater reduction in MMDs relative to placebo in no medication overuse.

From baseline to week 12, the proportion of patients who met the criteria for medication overuse decreased by 61.9% (P =.003) among the patients who received atogepant twice a day and by 52.1% (P =.01) among those who received atogepant once a day compared with by 38.3% of placebo recipients.

The safety profile of atogepant was similar among patients with and without acute medication overuse.

This study may not be generalizable for patients using opioids or barbiturates regularly, as these patients were excluded.

“This subgroup analysis of the PROGRESS trial demonstrated that atogepant is an effective and safe preventive treatment for patients with CM [chronic migraine], with and without acute medication overuse.”

Disclosure: This research was supported by AbbVie. Please see the original reference for a full list of disclosures