Safety, Tolerability, and Efficacy of Atogepant Added to OnabotulinumtoxinA for the Preventive Treatment of Chronic Migraine: A Phase 3, Multicenter, 24-week, Open-label Study
John Rothrock1, Umer Najib2, Jessica Ailani3, Sait Ashina4, Jia Bao5, Jonathan Smith5, Iryna Shakhmantsir5, Brett Dabruzzo5, Kimberly Pfleeger5, Andrew Blumenfeld6
1Inova Health, 2West Virginia University Hospitals, 3Medstar Georgetown Neurology, 4Beth Israel Deaconess Medical Center, Harvard Medical School, 5AbbVie, Inc., 6The Los Angeles Headache Center
Objective:
Evaluate the safety, tolerability, and efficacy of adding atogepant to onabotulinumtoxinA (onabotA) for the preventive treatment of chronic migraine (CM).
Background:
Despite recent advances in therapeutic management of CM, data on combination therapy is limited.
Design/Methods:
In this 24-week, Phase 3, open-label, multicenter study (NCT05216263), 75 participants on a stable dose of onabotA (155-200U) received add-on atogepant 60mg once daily. Primary safety endpoints included treatment-emergent adverse events (TEAEs), and efficacy assessments included changes in mean monthly migraine days (MMDs), and responder rates (RR) (≥50% and ≥75% MMDs) over weeks 1-12 and 13-24.
Results:
Participant mean age was 48 years; 89% were women, and 97% were white. Participants had an established CM diagnosis for 15 (13.27) years (mean (SD)) and had been treated with onabotA for 4 (3.45) years (mean (SD)). In the safety population (n = 75), the incidence of TEAEs was 65.3%. TEAEs occurring in ≥5% of patients were constipation (n=12, 16.0%), nausea (n=10, 13.3%), and urinary tract infection (n=6, 8.0%). Treatment-emergent serious AEs occurred in 2 participants, neither considered treatment-related by the investigators. In the modified intention-to-treat population (n = 72), the change from baseline of 14.34 MMDs was -6.45 MMDs [95% CI: -7.72, -5.19] across weeks 1-4, -6.89 MMDs [95% CI: −8.15, −5.62] across weeks 1-12 and −7.20 MMDs [95% CI: −8.49, -5.91] across weeks 13-24 (least square means). A ≥50% RR was achieved by 54.2% and 61.9% of participants, across weeks 1-12 and weeks 13-24 of combined treatment, respectively. A ≥75% RR was achieved by 30.6% and 38.1% participants, respectively.
Conclusions:
Combination management with onabotA and atogepant for CM appears to be safe and generally well-tolerated. Adding atogepant to onabotA resulted in clinically meaningful reductions in migraine days and improvement in RR, reflecting the potential benefit of utilizing combination therapy with distinct but complementary mechanisms of action for CM management.
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