The Lancet. Neurology · 2026
Tolerability, safety, and efficacy of atogepant versus topiramate in adults with migraine (TEMPLE): a randomised, head-to-head, phase 3b trial.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Reuter Uwe, Dycke Annelies Van, Versijpt Jan, Holle-Lee Dagny, Farkas Mark Kristof, Tepper Stewart J, Forero Giovanna, Luo Lei, Guo Hua, Cohen Eric, Dabruzzo Brett, Gandhi Pranav, Nagy Krisztian
Аннотация
BACKGROUND: Oral calcitonin gene-related peptide (CGRP) receptor antagonists such as atogepant have been approved for preventive treatment of migraine but have not been compared directly with conventional oral non-specific preventive treatments. Topiramate is a widely used conventional oral non-migraine-specific preventive treatment for migraine but its use is often limited by poor tolerability. We aimed to evaluate the tolerability, safety, and efficacy of atogepant versus topiramate in adults with migraine, to provide direct comparative evidence to help inform treatment selection.
METHODS: TEMPLE was a phase 3b, randomised, double-dummy, active-controlled trial with a 24-week double-blind treatment period and a 52-week open-label treatment period, done in sites with experience in diagnosing and treating migraine across 12 countries (Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Portugal, and the UK). Participants had a history of migraine and at least 4 migraine days per month on average across the 3 months before screening and during the combined screening and baseline period. Participants were randomly assigned 1:1 to atogepant (60 mg once daily) or topiramate (highest tolerated dose of 50 mg/day, 75 mg/day, or 100 mg/day) using interactive response technology. The primary endpoint assessed tolerability by measuring treatment discontinuation owing to treatment-emergent adverse events during the double-blind period in the safety population (all participants who received ≥1 dose of the study treatment during the double-blind period). Secondary efficacy endpoints related to clinical efficacy were at least 50% reduction from baseline in mean monthly migraine days and change from baseline in mean monthly migraine days during months 4-6 in the modified intention-to-treat population (all randomised participants who received ≥1 dose of study treatment, had an evaluable baseline period of eDiary data, and had ≥1 evaluable postbaseline 4-week [1 month] period of eDiary data within 24 weeks after first dose of study medication [month 1 to month 6], regardless of whether on study treatment or off study treatment). TEMPLE is registered with ClinicalTrials.gov (NCT05748483) and EU Clinical Trials Register (2022-501172-25-00); the double-blind period is completed and the open-label period is ongoing.
FINDINGS: Between Oct 7, 2023, and April 28, 2025, 730 participants were screened, 545 were randomly assigned, and 540 (479 [89%] female and 61 [11%] male, 517 [96%] White) were included in the safety population (atogepant n=273; topiramate n=267). Discontinuation due to treatment-emergent adverse events across the 24-week double-blind period was lower in the atogepant group (33 [12%] of 273) compared with the topiramate group (79 [30%] of 267; relative risk [RR] 0·4, 95% CI 0·3 to 0·6; p<0·0001). Treatment-related adverse events were reported by 153 (56%) of 273 participants in the atogepant group and 208 (78%) of 267 in the topiramate group. Serious treatment-emergent adverse events occurred in six participants on atogepant and in three participants on topiramate. One serious treatment-emergent adverse event (anaphylactic reaction in the atogepant group) was considered related to study drug. No deaths occurred. More participants experienced at least 50% reduction in mean monthly migraine days in the atogepant group (64% [173 of 270]) compared with the topiramate group (39% [101 of 257], RR 1·6, 95% CI 1·4 to 2·0, p<0·0001) and reduction from baseline in mean monthly migraine days was greater in the atogepant group (least squares mean -6·3 [SE 0·3]) than the topiramate group (-4·5 [0·3]; treatment difference -1·8 [-2·5 to -1·0]; p<0·0001).
INTERPRETATION: Atogepant 60 mg once daily showed better tolerability and efficacy across 24 weeks compared with topiramate. Although both topiramate and atogepant are established as effective oral migraine preventive treatments, their usefulness in clinical practice hinges on patients' ability to tolerate treatment. Our findings provide direct comparative evidence that might guide clinicians in selecting the most appropriate preventive therapy for their patients.
FUNDING: AbbVie.
METHODS: TEMPLE was a phase 3b, randomised, double-dummy, active-controlled trial with a 24-week double-blind treatment period and a 52-week open-label treatment period, done in sites with experience in diagnosing and treating migraine across 12 countries (Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Portugal, and the UK). Participants had a history of migraine and at least 4 migraine days per month on average across the 3 months before screening and during the combined screening and baseline period. Participants were randomly assigned 1:1 to atogepant (60 mg once daily) or topiramate (highest tolerated dose of 50 mg/day, 75 mg/day, or 100 mg/day) using interactive response technology. The primary endpoint assessed tolerability by measuring treatment discontinuation owing to treatment-emergent adverse events during the double-blind period in the safety population (all participants who received ≥1 dose of the study treatment during the double-blind period). Secondary efficacy endpoints related to clinical efficacy were at least 50% reduction from baseline in mean monthly migraine days and change from baseline in mean monthly migraine days during months 4-6 in the modified intention-to-treat population (all randomised participants who received ≥1 dose of study treatment, had an evaluable baseline period of eDiary data, and had ≥1 evaluable postbaseline 4-week [1 month] period of eDiary data within 24 weeks after first dose of study medication [month 1 to month 6], regardless of whether on study treatment or off study treatment). TEMPLE is registered with ClinicalTrials.gov (NCT05748483) and EU Clinical Trials Register (2022-501172-25-00); the double-blind period is completed and the open-label period is ongoing.
FINDINGS: Between Oct 7, 2023, and April 28, 2025, 730 participants were screened, 545 were randomly assigned, and 540 (479 [89%] female and 61 [11%] male, 517 [96%] White) were included in the safety population (atogepant n=273; topiramate n=267). Discontinuation due to treatment-emergent adverse events across the 24-week double-blind period was lower in the atogepant group (33 [12%] of 273) compared with the topiramate group (79 [30%] of 267; relative risk [RR] 0·4, 95% CI 0·3 to 0·6; p<0·0001). Treatment-related adverse events were reported by 153 (56%) of 273 participants in the atogepant group and 208 (78%) of 267 in the topiramate group. Serious treatment-emergent adverse events occurred in six participants on atogepant and in three participants on topiramate. One serious treatment-emergent adverse event (anaphylactic reaction in the atogepant group) was considered related to study drug. No deaths occurred. More participants experienced at least 50% reduction in mean monthly migraine days in the atogepant group (64% [173 of 270]) compared with the topiramate group (39% [101 of 257], RR 1·6, 95% CI 1·4 to 2·0, p<0·0001) and reduction from baseline in mean monthly migraine days was greater in the atogepant group (least squares mean -6·3 [SE 0·3]) than the topiramate group (-4·5 [0·3]; treatment difference -1·8 [-2·5 to -1·0]; p<0·0001).
INTERPRETATION: Atogepant 60 mg once daily showed better tolerability and efficacy across 24 weeks compared with topiramate. Although both topiramate and atogepant are established as effective oral migraine preventive treatments, their usefulness in clinical practice hinges on patients' ability to tolerate treatment. Our findings provide direct comparative evidence that might guide clinicians in selecting the most appropriate preventive therapy for their patients.
FUNDING: AbbVie.