Acute Treatment of Migraine
Ubrogepant may be an effective migraine treatment for patients with chronic migraine, multiple prior unsuccessful acute treatments, and those simultaneously using calcitonin gene-related peptide (CGRP) monoclonal antibodies, according to the results of a study presented at the American Academy of Neurology’s 2021 Virtual Annual Meeting.
To further explore the efficacy, tolerability, and safety of ubrogepant in these patient populations, the researchers conducted a cohort study of patients from a tertiary headache center. Within the 3-month study period, patients who were prescribed ubrogepant were contacted to complete a standardized questionnaire.
In addition to expanding the efficacy profile of ubrogepant for the treatment of migraine, the study also revealed potential adverse events and predictive factors for treatment success.
To learn more about these findings, Consultant360 reached out to the lead study author and session presenter, Chia-Chun Chiang, MD, who is an assistant professor of neurology in the Divisions of Headache and Cerebrovascular Neurology at Mayo Clinic in Rochester, Minnesota.
Consultant360: Prior to your study, there was no real-world data on the use of ubrogepant for the acute treatment of migraine in certain populations, despite being approved for use by the US Food and Drug Administration in December 2019. What knowledge gaps were you hoping to fill with your study?
Chia-Chun Chiang, MD: The efficacy and tolerability of ubrogepant were established from several clinical studies, including the ACHIEVE-I and ACHIEVE-II phase-3 clinical trials. However, several limitations exist. In the ACHIEVE-I and ACHIEVE-II trials, patients were excluded if they had 15 or more headache days per month (chronic migraine), using acute headache medications for more than 10 days per month, were concurrently using a CGRP monoclonal antibody (like erenumab, galcanezumab, fremanezumab, or eptinezumab), or if they had clinically significant cardiovascular or cerebrovascular diseases. This represents a large part of the clinical population for whom this medication is prescribed, especially in a tertiary headache clinic.
Prior to this study, no real-world patient experience studies had been published to validate the clinical trial findings in a population with the majority of patients having chronic migraine, complex comorbidities, multiple ineffective acute and preventive treatment trials, and concurrent use of other preventive medications, specifically CGRP monoclonal antibodies and onabotulinumtoxinA. Our goal was to address these limitations by conducting this study to assess the efficacy and tolerability of ubrogepant in a real-world patient population.
C360: The results of your study indicated that 2 hours after taking ubrogepant for 75% or more of all treated attacks, 19.1% of patients were able to achieve complete headache freedom, and 47.6% of patients experienced headache relief. What is the importance of these results?
CC: The real-world data was obtained from 106 patients from our headache clinic. Among those patients, 86.8% had chronic migraine and 50.5% had tried at least 3 triptans—a population very different from the clinical trial population.
We found that 19.0% of patients were able to achieve complete headache freedom 2 hours after taking ubrogepant for 75% or more of all treated attacks. Additionally, 47.6% of patients experienced headache relief 2 hours after taking ubrogepant for 75% or more of all treated attacks. The numbers are very similar to the efficacy data reported from the phase 3 clinical trials. Our study confirms and extends the efficacy of ubrogepant in the real-world population in which the majority of patients had multiple prior ineffective treatment trials. However, adverse event rates were higher in our population than reported in the clinical trials.
C360: Did any patient characteristics, such as age, race, or gender, play a role in the results of your study?
CC: We investigated whether demographic factors, including age and gender, associated with being a good responder to or having adverse effects from ubrogepant. We did not find any statistically significant associations. Our sample size was too small to determine whether race and ethnicity play a role, but it would be an important topic for future research projects.
C360: How will this additional knowledge on the efficacy, tolerability, and safety of ubrogepant impact the treatment landscape for patients with migraines?
CC: Our real-world study supports the efficacy and safety of ubrogepant in a real-world tertiary headache clinic where the majority of patients had chronic migraine and concurrent use of CGRP monoclonal antibodies. Our study addressed several limitations from the phase 3 clinical trials, including the efficacy and tolerability of ubrogepant in patients with chronic migraine, multiple ineffective treatment trials, and concurrently using a CGRP monoclonal antibody. We also reported the efficacy of ubrogepant in treating mild headache attacks (in the phase 3 clinical trials, patients were instructed to treat their headache when the pain was moderate to severe). Our data support the use of ubrogepant in a population not previously studied in clinical trials.
C360: What knowledge gaps remain concerning the use of ubrogepant for migraine treatment?
CC: In our study, we were also able to identify several factors, such as migraine with aura and prior successful responses to CGRP monoclonal antibodies and onabotulinumtoxinA, that were predictive of treatment response to ubrogepant. The exact mechanism behind those observations needs to be deciphered.
Also, we did not systemically investigate blood pressure changes in patients taking ubrogepant. Given elevated blood pressure has been reported in the postmarket setting from CGRP monoclonal antibodies, it is important to study whether ubrogepant is associated with elevated blood pressure when taken frequently. Although 16 of our patients had significant cardiovascular risk factors and no severe adverse events were reported, more studies are needed to establish the safety of ubrogepant in patients with significant cardiovascular comorbidities.
Chiang CC, Arca KN, Dunn RB, et al. Real-world efficacy, tolerability and safety of ubrogepant. Headache. 2021. Published online February 5, 2021. doi: https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.14062