Atogepant Outperforms Topiramate for Migraine Prevention

TOPLINEAtogepant, a calcitonin gene-related peptide receptor antagonist, yielded lower rates of discontinuation due to treatment-emergent adverse events (TEAEs) and showed better efficacy for migraine prevention than the anticonvulsant topiramate, a phase 3b randomized clinical trial showed.METHODOLOGYResearchers conducted a phase 3b, randomized, double-blind, double-dummy, active-controlled trial (TEMPLE) at 73 sites across 12 countries with a 24-week double-blind treatment period.Overall, 545 adults with a history of migraine for at least 12 months and at least 4 migraine days per month were randomly assigned in a 1:1 ratio to receive either atogepant 60 mg/d or topiramate at the highest tolerated dose (50 mg/d, 75 mg/d, or 100 mg/d). Topiramate was titrated up starting with 25 mg/d and increased by 25 mg/d in weekly increments with the aim of reaching the target dose of 100 mg/d over a 6-week period, followed by an 18-week maintenance phase.The primary outcome was treatment discontinuation due to TEAEs during the 24-week double-blind treatment period in the safety population (n = 540; mean age, 39.6 years; 89% female; 96% White). Secondary efficacy endpoints assessed in the modified intention-to-treat population (n = 527) were a ≥ 50% reduction in mean monthly migraine days and a change from baseline in mean monthly migraine days during months 4-6 of the double-blind treatment period.Secondary functional outcomes measured in the modified intention-to-treat population were changes from baseline in Headache Impact Test-6 (HIT-6) and Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive domain scores at week 24, a rating of “much better” or “very much better” on the Patient’s Global Impression of Change (PGIC) scale at week 24, and a change from baseline in Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-CF) Abilities Subset-Short Form 6a version 2.0 scores at week 6.TAKEAWAYDiscontinuation due to TEAEs was lower in the atogepant vs topiramate group across the 24-week double-blind treatment period (12% vs 30%; relative risk [RR], 0.4; P < .0001).A greater proportion of participants in the atogepant vs topiramate group showed a ≥ 50% reduction in mean monthly migraine days during months 4-6 of the double-blind treatment period (64% vs 39%; RR, 1.6; P < .0001).The atogepant group showed greater improvement than the topiramate group at week 24 in HIT-6 (least-squares mean, -11.7 vs -7.4; P < .0001) and MSQ v2.1 Role Function-Restrictive domain (least-squares mean, 33.5 vs 23.1; P < .0001) scores. A higher proportion of participants in the atogepant group than in the topiramate group responded “much better” or “very much better” at week 24, as assessed using the PGIC scale (69% vs 37%; RR, 1.9; P < .0001).The atogepant group had a greater change from baseline in the PROMIS-CF Abilities score at week 6 than the topiramate group (least-squares mean, 5.2 vs 0.2; P < .0001).IN PRACTICE“In TEMPLE, atogepant was associated with superior tolerability and efficacy compared with topiramate for the preventive treatment of migraine and provides direct comparative evidence to guide clinicians in migraine management,” the study authors wrote.“These findings reinforce a fundamental principle of migraine prevention: The value of a treatment depends not only on efficacy but also on patients’ ability to tolerate and persist with therapy. TEMPLE provides clinically meaningful comparative evidence that extends beyond conventional efficacy endpoints,” Cristina Tassorelli, University of Pavia, Pavia, Italy, wrote in an accompanying editorial.SOURCEThe study was led by Uwe Reuter, MD, Charité Universitätsmedizin Berlin, Berlin, Germany. It was published online on July 23 in The Lancet Neurology.LIMITATIONSThe study was limited by predominant inclusion of female and White individuals, lack of a placebo group, potential contribution of the active-controlled design to nocebo responses, potential unblinding due to differences in the drugs’ side-effect profiles, stringently defined dosing regimens, and potential adverse events at the end of the up-titration phase of topiramate. Additionally, PROMIS-CF has been validated for migraine only qualitatively.DISCLOSURESThe study was funded by AbbVie, maker of atogepant. Disclosure information for study investigators and the author of the editorial is available in the original study publication.This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.