Safety and Efficacy of Ubrogepant for Acute Migraine in Patients Taking Preventive Therapies

October 2022

Acute therapies for migraines are not sufficient for some patients who also need preventive therapies. Ubrogepant, an oral antagonist of the calcitonin gene-related peptide receptor, is an approved therapy for acute migraines. Whether concomitant preventive medications affect the safety or efficacy of ubrogepant is unknown.

To evaluate the safety and efficacy of the acute use of ubrogepant in patients taking concomitant preventive therapies, researchers performed post-hoc subgroup analyses of clinical trial data. The data came from ACHIEVE I and ACHIEVE II phase 3 randomized clinical trials and a long-term extension trial for ubrogepant as an acute therapy in patients with migraines with or without aura.

Patients enrolled in the trials had a ≥1-year history of migraine and 2 to 8 migraines per month. A subset of patients in each trial was also taking preventive therapies. Among the patients in the trial subgroups that took preventive therapies, 44% to 52% used anticonvulsants, 18% to 26% used antidepressants, and 16% to 21% used beta-blockers.

For the ACHIEVE I and II efficacy trials, data from 2247 patients who received placebo, 50 mg, or 100 mg of ubrogepant for a single acute migraine attack were included in the post-hoc efficacy and safety analyses. In total, 18.6% of these patients used preventive medications.

For the long-term extension safety trial, the post-hoc analysis included pooled data from 813 patients who had been enrolled in the ACHIEVE trials. These patients had taken 50 mg or 100 mg of ubrogepant as needed for up to 1 year. A total of 17.5% of these patients used preventive medications.

In the pooled efficacy analysis using data from the ACHIEVE I and II trials, researchers found that patients taking ubrogepant for a migraine attack had significantly greater pain freedom after 2 hours compared with placebo. Within the ubrogepant subgroups, patients who took concomitant preventive medication had similar responses to ubrogepant as patients who did not take preventive medication. Furthermore, among patients taking ubrogepant, no significant difference was seen between patients who did or did not use preventive medications for achieving pain relief or in the absence of their most bothersome symptom 2 hours after the migraine attack.

Similarly, the researchers found no significant differences in the rates of treatment-related adverse events (TRAEs), serious AEs, or discontinuation caused by TRAEs between patients taking ubrogepant with concomitant preventive medication and those taking ubrogepant without preventive medication. Between 8% and 11% of patients in the trials who took ubrogepant had ≥1 TRAEs, but no TRAE was considered to be serious.

The most common TRAEs differed by trial. In the single-event ACHIEVE I and II trials, nausea, somnolence, and dry mouth were the most common TRAEs. In the 1-year long-term extension study, the most common TRAE was upper respiratory infection.

The researchers identified some limitations to the study. The efficacy data were based on the results of a single migraine attack in each patient so the efficacy of repeated ubrogepant use with or without preventive medications is unknown. The statistical approaches were also limited by the small sample sizes between subgroups. Furthermore, the researchers were unable to analyze the efficacy and safety of ubrogepant by specific preventive medication classes because of small sample sizes.

“The results of this study indicate that ubrogepant is safe to use with the preventive medications for migraine and can be applied when being used in real-world practice,” the researchers concluded.

Funding for the study was from Allergan.


Blumenfeld AM, Knievel K, Manack Adams A, et al. Ubrogepant is safe and efficacious in participants taking concomitant preventive medication for migraine: a pooled analysis of phase 3 trials. Adv Ther. 2022;39(1):692-705.

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