Atogepant Effective in Treating Chronic Migraine With Medication Overuse

Recently published post-hoc data from the phase 3 PROGRESS trial (NCT03855137) revealed that atogepant (Qulipta; AbbVie), an FDA-approved medication for chronic and episode migraine, was effective in patients with and without acute medication overuse.¹

The 12-week trial featured adults with at least 1 year of chronic migraine (CM) who were experiencing at least 15 monthly headache days (MHDs) and at least 8 monthly migraine days (MMDs) during the baseline period. Of the 755 participants in the modified intent-to-treat population, 500 (66.2%) met baseline acute medication (placebo: 68.7%; atogepant 30 mg BID: 63.6%; atogepant 60 mg QD: 66.4%). Acute medication overuse was defined as taking triptans for at least 10 days, ergots for at least 10 days, simple analgesics for at least 15 days, or any combination of triptans, ergots, or simple analgesics for at least 10 days per 28-day period.

Led by Peter J. Goadsby, MD, PhD, FRS, director of the National Institute for Health Research and professor of neurology at King’s College London, the primary end point was change from baseline in mean MMDs across the 12-week treatment period. Coming into the study, participants from Europe (73%) and East Asia (70%) had higher percentages of those with acute medication overuse than North America (54%). Overall, baseline mean MMDs ranged from 19.0 to 19.7 and 17.8 to 18.4 in participants with and without acute medication overuse across the treatment groups, respectively.

Results showed that the least-square mean difference from placebo in the acute medication overuse subgroup was –2.7 days (95% CI, –4.0 to –1.4) with atogepant 30 mg BID and –1.9 days (95% CI, –3.2 to –0.6) with atogepant 60 mg QD. Similarly, the least-square mean difference from placebo in the subgroup without acute medication overuse was –1.7 days (95% CI, –3.5 to 0.2) with atogepant 30 mg BID and –1.6 days (95% CI, –3.5 to 0.3) with atogepant 60 mg QD.

In participants with acute medication overuse, a reduction of at least 50% in MMDs was achieved by 44.7% of those treated with atogepant 30 mg BID and 41.8% with atogepant 60 mg QD, compared with 24.9% in the placebo arm. For those without acute medication overuse, this reduction was achieved by 39.1% of those in the atogepant 30 mg BID group, 39.5% for those on atogepant 60 mg QD, and 28.6% of those in the placebo group.

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Across the 12-week period, investigators also saw greater reductions in mean monthly acute medication use days with atogepant. All told, the least square mean difference from placebo in the acute medication overuse subgroup was −2.8 days (95% CI −4.1 to −1.6) with atogepant 30 mg BID and −2.6 days (95% CI −3.9 to −1.3) with atogepant 60 mg QD. In the subgroup without acute medication overuse, the LSMD from placebo was −1.8 days (95% CI −3.2 to −0.4) with atogepant 30 mg BID and −1.5 days (95% CI −3.0 to −0.1) with atogepant 60 mg QD.

Atogepant, a calcitonin gene-related peptide antagonist, also led to reductions in acute medication overuse. Using those who met acute medication overuse criteria after the 12-week period, Investigators observed reductions of 61.9% (nominal P = .003) and 52.1% (nominal P = .01) in the proportion of patients on atogepant 30 mg BID and 60 mg QD groups, respectively. For comparison, 38.3% of those on placebo experienced reductions as well. Among atogepant-treated patients, reductions were similar regardless of the type of acute medication used.

Regardless of whether patients had acute medication overuse, treatment with atogepant led to improvements in patient-reported outcomes, specifically HIT-6 total score, after 12 weeks. At that time point, the treatment difference between active and placebo groups passed the established minimally important difference for the HIT-6 total score, at least a 2.3-point reduction. In addition, atogepant-treated patients saw greater change from baseline in MSQv2.1, including RFR, RFP, and EF domains, regardless of acute medication overuse status.

Atogepant, originally approved in September 2021 as a treatment for episodic migraine, had its indication expanded in April 2023 to include patients with CM. The approval was granted based on data from PROGRESS, in which 60-mg atogepant resulted in significant reduction in mean MMDs compared with placebo over 12 weeks of treatment.

REFERENCE
1. Goadsby PJ, Friedman DI, Holle-Lee D, et al. Efficacy of atogepant in chronic migraine with and without acute medication overuse in the randomized, double-blind, phase 3 PROGRESS trial. Neurology. 2024;103(2). doi:10.1212/WNL.0000000000209584