Ubrogepant, the first oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine, was also effective in the prodrome period in a recent randomized trial.
Researchers conducted the phase 3 double-blind trial at 75 U.S. facilities to evaluate the efficacy, safety, and tolerability of ubrogepant versus placebo for migraine when given during the prodrome, the earliest phase of a migraine attack when nonaura symptoms precede headache onset. Adults with at least a one-year history of migraine with or without aura as well as a history of two to eight migraine attacks per month with moderate to severe headache in each of the three months before screening were randomly assigned to placebo to treat the first qualifying prodrome event and ubrogepant, 100 mg, to treat the second qualifying prodrome event, or vice versa. A qualifying prodrome event was defined as prodromal symptoms that the patient judged were likely to be followed by a headache within one to six hours. There was a seven-day washout period between the first and second prodrome event.
The primary end point was absence of moderate or severe headache within 24 hours after taking the study drug. Efficacy analyses were done using a modified intention-to-treat analysis, which was defined as all randomly assigned patients who had at least one headache assessment within 24 hours after taking the study drug during the treatment period, while the safety population included all treated participants who took the study drug at least once. The results of the study, which was funded and conducted by AbbVie, were published Nov. 15 by The Lancet.
Five hundred eighteen patients were randomly assigned to treatment between Aug. 21, 2020, and April 19, 2022. There were 480 patients in the safety population and 477 in the modified intention-to-treat population; of the 480 patients, mean age was 42.3 years, 88% were female, and 12% were male. Absence of moderate or severe headache within 24 hours of treatment was observed in 190 (46%) of 418 qualifying prodrome events treated with ubrogepant and 121 (29%) of 423 treated with placebo (odds ratio, 2.09 [95% CI, 1.63 to 2.69]; P<0.0001). Within 48 hours, the corresponding numbers were 159 (41%) of 391 events treated with ubrogepant and 100 (25%) of 407 events treated with placebo (odds ratio, 2.13 [95% CI, 1.63 to 2.78]; P<0.0001). The absence of any headache within 24 hours after treatment of a qualifying prodrome event was seen in 103 (24%) of 434 events treated with ubrogepant and 61 (14%) of 439 events treated with placebo (odds ratio, 1.93 [95% CI, 1.39 to 2.66]; P<0.0001). Adverse events within 48 hours after study drug administration occurred in 77 (17%) of 456 qualifying prodrome events treated with ubrogepant and after 55 (12%) of 462 events treated with placebo.
The authors noted that their study size was small and that there is some controversy about whether patients with migraine are able to predict headache onset by identifying prodrome symptoms, among other limitations. They concluded that ubrogepant, 100 mg, taken during the prodrome significantly reduced development of moderate or severe headache for up to 48 hours after administration and development of a headache of any intensity and functional disability for 24 hours.
“These results emphasise the clinical value of identifying the prodrome in people with migraine and highlight an important opportunity to intervene in the earliest phase of a migraine attack to prevent progression to the headache phase, reduce disability, and improve outcomes,” the authors wrote. They called for further study of the efficacy of acute medications taken during the prodrome phase versus the mild pain phase in patients with migraine.