Effect of Ubrogepant on Patient-Reported Outcomes When Administered During the Migraine Prodrome

Background and Objectives Ubrogepant is a calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine. The PRODROME trial previously demonstrated that ubrogepant treatment during prodrome prevents the onset of moderate or severe headache. In this analysis of the PRODROME trial, the benefits of ubrogepant treatment during the prodrome on patient-reported outcomes (PROs) are evaluated. Methods PRODROME was a multicenter, randomized, double-blind, placebo-controlled, crossover trial that enrolled adults who experienced 2–8 migraine attacks per month with moderate-severe headache pain. Eligible participants treated 2 qualifying prodrome events, defined as a migraine attack with prodromal symptoms when the participant was confident a headache would follow within 1–6 hours. Participants were randomized to treatment sequence A (placebo then ubrogepant 100 mg) or sequence B (ubrogepant 100 mg then placebo). This analysis evaluated the ability to function normally over 24 hours (secondary end point) and at specific time points after dose (additional end point). Other PRO end points included activity limitation over 24 hours and satisfaction with study medication at 8 and 24 hours. Results Of 518 randomized participants, 477 comprised the modified intent-to-treat population. After treatment of qualifying prodrome events, a significantly greater ability to function normally over 24 hours was observed for participants after treatment with ubrogepant 100 mg compared with placebo (odds ratio [OR] 1.66, 95% CI 1.40–1.96; p < 0.0001). As early as 2 hours after dose, a greater proportion of ubrogepant-treated participants reported “no disability, able to function normally” compared with placebo (OR 1.76, 95% CI 1.32–2.35; nominal p = 0.0001). Ubrogepant administered during the prodrome was also associated with a greater reduction in activity limitations over 24 hours after dose (OR 2.07, 95% CI 1.61–2.67; nominal p < 0.0001). At 8 and 24 hours after dose, rates of being “satisfied” or “extremely satisfied” were greater for ubrogepant than for placebo (8 hours: OR 2.37, 95% CI 1.78–3.15; nominal p < 0.0001; 24 hours: OR 2.32, 95% CI 1.78–3.02; nominal p < 0.0001). Discussion Ubrogepant 100 mg administered during the prodrome was associated with significantly greater ability to function normally, greater reduction in activity limitations over 24 hours, and greater satisfaction with study medication, compared with placebo. Glossary AE = adverse event; AHS = American Headache Society; CGRP = calcitonin gene–related peptide; FDA = Food and Drug Administration; FDS = Functional Disability Scale; GLMM = generalized linear mixed model; HRQoL = health-related quality of life; mITT = modified intent-to-treat; OR = odds ratio; PRO = patient-reported outcome.