麻豆传媒

Treatment with oral ubrogepant (Ubrelvy) during the migraine prodrome led to more patients being able to function normally, a prespecified secondary endpoint analysis of the phase III PRODROME trial showed.

After treatment of prodrome events that precede a migraine, the odds of reporting the ability to function normally over 24 hours was significantly greater for those who took the calcitonin gene-related peptide receptor (CGRP) receptor antagonist compared with placebo recipients (OR 1.66, 95% CI 1.40-1.96, P<0.0001), reported Richard B. Lipton, MD, of the Albert Einstein College of Medicine in New York City, and colleagues.

At the time of treatment, participants in the ubrogepant and placebo arms were able to function normally during only 27% and 25.2% of qualifying prodrome events, respectively, which increased to 88.9% and 84.7% over 24 hours, according to the findings in .

In addition, a greater proportion of patients reported "no disability, able to function normally" as early as 2 hours after taking ubrogepant (37% vs 26.1% with placebo; OR 1.76, 95% CI 1.32-2.35, nominal P=0.0001).

At 8 and 24 hours, rates of being "satisfied" or "extremely satisfied" were greater with ubrogepant versus 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)

"Treatment with ubrogepant when administered during both the prodromal and headache phases can allow patients to achieve freedom from pain, absence of most bothersome symptoms, and a return to normal daily activities," Lipton and colleagues wrote.

Ubrogepant is currently approved for the acute treatment of migraine with or without aura in adults -- other CGRP antagonists are approved for migraine prevention or both prevention and acute treatment.

PRODROME sought to evaluate ubrogepant's safety and efficacy for treatment ahead of a migraine attack. Patients may not always describe or ask about these precursor symptoms, but found that after patients received prodrome education, 77% reported experiencing them.

Prodromal symptoms can include cognitive, mood, sensory, or hormonal changes, like yawning, nausea, memory problems, or sensitivity to light and sound. Those with more severe migraine attacks may have more prodrome symptoms, and those with more frequent prodrome symptoms may have longer migraine attacks, and more nausea.

from PRODROME -- a randomized crossover trial -- showed that more patients taking ubrogepant reported absence of a moderate/severe-intensity headache within 24 hours compared with placebo. The current analysis of the trial evaluated secondary patient-reported outcomes.

Elizabeth Loder, MD, PhD, of Harvard Medical School in Boston, who was not involved in the study, told 麻豆传媒 that the highly selective inclusion criteria for the trial might have limited the number of patients who could benefit from ubrogepant.

Participants had to have migraine, but also be able to reliably identify migraine attacks with prodrome, which not everyone with migraine can do. Even then, Loder said, they had to predict migraine with at least 75% accuracy over 60 days.

Of the 1,087 patients assessed for eligibility, 317 were excluded for not meeting inclusion criteria.

"However, even in this enriched population of patients with reliable prodromal symptoms, the difference between placebo and active treatment was modest," Loder said. For example, 65.4% of participants who took ubrogepant reported being "not at all limited" or "a little limited" over 24 hours after the dose compared with 47.8% of those in the placebo group (OR 2.07, 95% CI 1.61-2.67, nominal P<0.0001).

"Is that worth it, and for whom?" Loder asked. "In thinking about applying these results in clinical practice, doctors and patients should consider whether an individual patient would have met criteria to enter this study -- that is, are they reliably able to identify the early warning signs of a migraine?"

Still, she acknowledged, "this study does stand as good evidence that treatment during prodrome with ubrogepant provides an improvement in ability to function normally compared to placebo. It seems likely that this result will apply to other abortive treatments, not just ubrogepant."

For this prespecified secondary endpoint analysis, 518 patients were randomized to treatment sequence A (placebo then ubrogepant 100 mg) or sequence B (ubrogepant 100 mg then placebo), and 477 patients comprised the modified intent-to-treat population. Eligible participants treated two qualifying prodrome events (449 during placebo and 448 during ubrogepant treatment), defined as a migraine attack with prodromal symptoms when the participant was confident a headache would follow within 1 to 6 hours.

Mean age was 42.3 years, 87.7% were women, and 88.1% were white. Of the randomized participants, 438 (84.6%) completed the trial.

Participants rated their ability to function normally in an eDiary at 1, 2, 3, 4, 6, 8, 24, and 48 hours using the Functional Disability Scale, a 4-point scale with lower numbers indicating higher functioning -- a score of 0 indicates "no disability, able to function normally." They recorded activity limitations and satisfaction with the drug using similar 5- and 7-point scales.

Most of the patient-reported outcome measures had 24-hour recall periods, which could have introduced recall bias. Patients also didn't have to treat the same prodrome symptom for first and second qualifying prodrome events, which could have resulted in differential outcome responses. In addition, neck stiffness counted as a prodromal symptom, but there is still debate over whether neck pain should be considered prodromal or a symptom of migraine itself.

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