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The chronopharmacology of atogepant in migraine prevention: A real-world evaluation of influence of timing of administration on effectiveness and tolerability

delete2026-03-25
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PRE
AI
L
Luigi Francesco Iannone
G
Gabriele Sebastianelli
F
Federico De Santis
M
Michele Corrado
M
Marilena Marcosano
R
Raffaele Ornello
L
Licia Grazzi
D
Danilo Antonio Montisano
F
Francesco De Cesaris
A
Antonio Munafò
G
Giulia Vigani
G
Gianluca Avino
M
Michele Trimboli
M
Maria Albanese
A
Antonio Russo
G
Giorgio Dalla Volta
M
Marina Romozzi
P
Paolo Calabresi
F
Flavia Lo Castro
A
Alberto Boccalini
P
Paola Merlo
M
Maria Pia Prudenzano
M
Maria Rosaria Valente
I
Innocenzo Rainero
G
Giada Giuliani
M
Marta Altieri
L
Luisa Fofi
A
Alberto Doretti
G
Gloria Vaghi
F
Francesca Pistoia
C
Claudia Lanni
A
Alessandra Rufa
S
Stefania Battistini
G
Gianluca Coppola
P
Pierangelo Geppetti
S
Simona Sacco
S
Simona Guérzoni
C
Claudia Altamura
F
Fabrizio Vernieri
DOI:10.1177/03331024261416490delete
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Abstract

Abstract

En 中文
<jats:sec> <jats:title>Aim</jats:title> <jats:p>To assess whether the timing of atogepant administration influences its tolerability and effectiveness over 12 weeks in patients with episodic and chronic migraine in a real-world setting.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This is a post-hoc analysis of the STAR study, a prospective, Italian, multicenter study evaluating atogepant 60 mg for migraine prevention. Data were collected at baseline (T0) and after the first 12 weeks (T3) of treatment. Patients were grouped by administration timing (morning vs. evening) and by administration with or without food. Changes in monthly headache days (MHDs), monthly migraine days (MMDs), and Migraine Disability Assessment (MIDAS) were measured. Tolerability was evaluated via adverse events (AEs). Linear mixed-effects models (LMMs) were used.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> Eighty-one patients (86% females, mean age 50.8 ± 13.7 years) were included. At T3, MMDs decreased from 16.6 to 9.7 (p &lt; 0.001) and MHDs from 19.8 to 11.9 (p &lt; 0.001); 60% of patients achieved ≥50% reduction in MMDs. AEs occurred in 34 (42%) participants. Atogepant was taken in the morning by 57% and in the evening by 43% of patients. Fifty-seven out of 81 participants (70.4%) took atogepant with food. No significant differences in MMDs, MHDs, or AEs emerged between morning and evening users. Evening users had higher baseline MIDAS scores (estimated marginal means [EMMs]: 69.9 vs. 39.9, p = 0.034) that showed a greater reduction compared to morning users ( <jats:italic toggle="yes">F</jats:italic> (1,63) = 6.29, <jats:italic toggle="yes">p</jats:italic>  = 0.015), reaching similar final scores after 12 weeks (EMMs: 25.1 vs. 23.8). No difference in atogepant effectiveness and tolerability according to intake with or without food, except for a reduction in MHDs for patients who took atogepant without food (EMMs from 21.3 to 9.9 vs with food: EMMs from 18.4 to 12.7; <jats:italic toggle="yes">F</jats:italic> (1,79) = 8.553, <jats:italic toggle="yes">p</jats:italic>  = 0.005). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Atogepant significantly reduced migraine burden over 12 weeks in a real-world setting. Overall, the timing of atogepant administration did not affect its effectiveness or tolerability. However, a greater reduction in MIDAS scores was observed among evening users. Whether this reflects a pharmacological advantage or a ceiling effect remains unclear. Taking atogepant without food was associated with a significantly greater reduction in MHDs, whereas changes in MMDs and MIDAS scores did not differ between groups. Long-term and dedicated studies are needed to evaluate and confirm these findings.</jats:p> </jats:sec> <jats:sec> <jats:title>Trial Registration</jats:title> <jats:p>The main study (STAR) was preregistered on clinicaltrial.gov, NCT06414044.</jats:p> </jats:sec>
Keywords:
atogepant
migraine prevention
timing of administration
tolerability
effectiveness

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Cephalalgia cover
Cephalalgia
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