A secondary analysis of the PRODROME trial found that ubrogepant, an oral calcitonin gene–related peptide receptor antagonist, significantly improved function when taken during the migraine prodrome phase, before headache onset. This randomized, double-blind, placebo-controlled crossover trial emphasized the importance of early treatment in migraine management.
The multicenter U.S. study, results of which were published in Neurology, was conducted from August 2020 to April 2022 and enrolled 477 adults aged 18 to 75 years with two to eight migraine attacks per month with moderate-to-severe headache. Participants were required to identify prodrome symptoms followed by headache in at least 75% of attacks.
The trial consisted of a 60-day screening period and a 60-day double-blind treatment period. Participants were randomized 1:1 to receive ubrogepant at 100 mg or placebo, taken during the prodrome phase in a two-period crossover design. Randomization was performed via an interactive web response system, and blinded dosing cards were used.
Electronic diaries captured functional disability (4-point scale), activity limitations (5-point scale), and satisfaction with treatment (7-point scale). The mean participant age was 42.3 years, 87.7% were female, and 88.1% were White. The most common prodromal symptoms were light sensitivity (46%–51%), neck pain (43%–47%), and mood changes (36%–42%). At baseline, only 25% to 27% of participants could function normally during the prodrome phase.
Ubrogepant significantly improved the ability to function normally over 24 hours compared to placebo (odds ratio [OR = 1.66; 95% confidence interval [CI] = 1.40-1.96; P<.0001). By 2 hours post-dose, more participants reported no functional disability with ubrogepant (OR = 1.76; 95% CI = 1.32-2.35; nominal P=.0001), an effect sustained through 24 hours (OR = 1.44; 95% CI = 1.01-2.06; nominal P=.0457).
Ubrogepant also resulted in a greater reduction in activity limitations at 24 hours (OR = 2.07; 95% CI = 1.61-2.67; nominal P<.0001) and higher treatment satisfaction at 8 hours (OR = 2.37; 95% CI = 1.78-3.15; nominal P<.0001) and 24 hours (OR = 2.32; 95% CI = 1.78-3.02; nominal P<.0001) compared to placebo. Notably, these improvements were observed not just during the headache phase, but also during the prodrome phase itself.
Adverse events occurred in 16.9% (77 of 456) of participants receiving ubrogepant and 11.9% (55 of 462) of those receiving placebo. The most common adverse events seen with ubrogepant were nausea (5.0%), fatigue (2.6%), dizziness (2.4%), and somnolence (2.4%).
The study authors noted some limitations, including a 24-hour recall period for some measures potentially introducing bias and the racial homogeneity of the study population (88.1% White).
"...These results demonstrate the functional benefits of ubrogepant for the treatment of acute migraine when administered during the prodrome," the investigators concluded.
Full disclosures can be found in the study.
