Efficacy of ubrogepant and atogepant in males and females with migraine: A secondary analysis of randomized clinical trials

Abstract

Background: Published evidence supporting efficacy of calcitonin gene-related peptide receptor antagonists as acute migraine treatments in males is limited. Methods: To fill the gap, we present male and female data from four ubrogepant and four atogepant randomized, double-blind, placebo-controlled trials for acute and preventive treatment of migraine, respectively. Acute outcomes included 2-h pain freedom and absence of most bothersome symptom (co-primary; headache-phase randomized, double-blind, placebo-controlled trials); absence of moderate-to-severe headache within 24 h (primary; prodrome randomized, double-blind, placebo-controlled trial). Preventive outcome included change from baseline in mean monthly migraine days across 12 weeks (primary). Results: Pooled data from phase 3 headache-phase ubrogepant randomized, double-blind, placebo-controlled trials showed similar rates of pain freedom (19.4% vs 21.1%) and absence of most bothersome symptom (35.1% vs 39.0%) 2 h post-dose between males and females, respectively. Time course of pain freedom and absence of most bothersome symptom over 48 h was similar between male and female subgroups. Comparable reductions in mean monthly migraine days across 12-week treatment periods were found between males and females treated with atogepant 60 mg once-daily in pooled episodic migraine and chronic migraine randomized, double-blind, placebo-controlled trials. Conclusion/Interpretation: In ubrogepant and atogepant randomized, double-blind, placebo-controlled trials, although analysis power for males is limited due to small sample sizes, evidence supports similar treatment effects in males and females with migraine. Trial registration: ClinicalTrials.gov: NCT02828020; NCT02867709; NCT04492020; NCT01613248; NCT02848326; NCT03777059; NCT04740827; NCT03855137