Ubrogepant Administration in Prodromal Phase Helps Reduce Migraine Attacks

Ubrogepant is well-tolerated and effective for the treatment of a migraine attack when taken during the prodromal phase, according to study findings published in the journal The Lancet.

Ubrogepant is a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist that has been approved for the treatment of acute migraine.

To evaluate the safety and efficacy of ubrogepant use during the prodrome, researchers conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, crossover trial (UBR Prodrome; ClinicalTrials.gov Identifier: NCT04492020) at 75 sites in the United States between 2020 to 2022. After a screening period, a subset of patients (n=480) was randomly assigned to receive 100 mg ubrogepant followed by placebo or placebo followed by ubrogepant to treat a qualifying prodrome event with a 7-day wash-out period between treatments. The primary outcome was the absence of headache of moderate or severe intensity within 24 hours of treatment.

A total of 4802 qualifying prodrome events were reported by 920 participants during the screening period. The most common prodromal symptoms included sensitivity to lights (57%), fatigue (50%), neck pain (42%), and dizziness (28%). Prodromal symptoms progressed to headache between 1 and 6 hours in ³75% of qualifying prodrome events.

Among patients who were randomly assigned to placebo (n=247; mean age, 41.7; 97% Women; 87% White) or ubrogepant (n=233; mean age, 42.9; 88% women; 90% White), 43% and 47% had migraine without aura, they had experienced migraine for a median of 20.0 and 22.8 years, and 22% and 17% had a history of using preventative migraine medications, respectively.

Overall, 46% reported absence of moderate or severe headache within 24 hours of taking ubrogepant compared with 29% after taking placebo. These rates indicated that ubrogepant better prevented headache than placebo (odds ratio [OR], 2.09; 95% CI, 1.63-2.69; P <.0001).

Similarly, ubrogepant was favored over placebo for secondary outcomes of absence of moderate or severe headache within 48 hours (OR, 2.13; 95% CI, 1.63-2.78; P <.0001) and absence of any intensity headache within 24 hours (OR, 1.93; 95% CI, 1.39-2.66; P <.0001).

Any adverse event occurred among 17% after ubrogepant and 12% after placebo administration. The most common adverse events after taking ubrogepant included nausea (5%), fatigue (3%), dizziness (2%), and somnolence (2%).

The major limitation of this study was the fact that use of prodromal symptoms to predict migraine onset remains controversial. However, the screening period found that most prodromal symptoms progressed to migraine within 6 hours.

“These results emphasise [emphasize] 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 researchers concluded.

Disclosures: This research was supported by AbbVie. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.