Comparative analysis of real-world acute prescription migraine therapy outcomes: Insights from the HeAD-US study

Triptans have long served as the primary acute migraine treatment, whereas gepants represent a newer, non-vasoconstrictive alternative. Although clinical trials have explored efficacy within each class, head-to-head studies are lacking, and real-world data on optimal treatment response and patient-level predictors of outcomes remain limited. We leverage cross-sectional data from the Headache Assessment via Digital Platform in United States study to conduct real-world comparisons of triptans and gepants for 2-h pain freedom (2hPF) and 24-h pain relief (24hPR), and to identify demographic, clinical, and treatment-related predictors of these outcomes.

Head-US is a survey conducted between September and December of 2023 among users of the Migraine Buddy application (Aptar, Crystal Lake, IL). Eligible participants completed the survey, met ICHD-3 criteria for migraine, and reported using acute monotherapy with gepants or a triptan. Primary outcomes, 2hPF and 24hPR posttreatment, were assessed using the Migraine Treatment Optimization Questionnaire-6 item. Potential predictors included demographic factors, clinical measures, and treatment-related factors.

Among 1570 eligible respondents, 567 used gepants and 1003 used a triptan. Mean age was 43.35 years (standard deviation = 13.04), and 91.2% were female. Gepant users demonstrated 36% higher odds of achieving 24hPR compared to triptan users (adjusted odds ratio = 1.36, 95% confidence interval: 1.09-1.71), although there were no significant differences the 2hPF outcome. Reduced odds of adequate 2hPF were associated with higher migraine symptom severity, high-frequency episodic migraine, chronic migraine, severe pain intensity, and severe migraine disability. Odds of achieving 24hPR were reduced in those with higher attack frequency, severe migraine disability, and preventive medication use. Predictors of treatment response were similar in the pooled sample and in those using gepants and in those using triptans.

In this large, real-world cohort, triptans and gepants did not significantly differ for 2hPF, but gepants demonstrated a significant advantage for 24hPR. Clinical features such as symptom severity, headache frequency, disability, and comorbid treatment burden were important predictors of treatment response. These findings support the need for larger, head-to-head clinical trials definitively comparing these medication classes for migraine management and may inform personalized selection of acute migraine therapies in clinical practice.