Real-world Efficacy, Tolerability, and Safety of Ubrogepant

Chia-Chun Chiang MD; Karissa N. Arca MD; Rachel B. Dunn BS; Marlene E. Girardo MS; Jaxon K. Quillen BS; David W. Dodick MD; Amaal J. Starling MD


Headache. 2021;61(4):620-627. 

In This Article

Abstract and Introduction


Objective: To assess the real-world efficacy, tolerability, and safety of ubrogepant in a tertiary headache center.

Background: The efficacy and safety of ubrogepant for the acute treatment of migraine were established in phase 3 randomized controlled trials. However, there is no real-world data of patient experience with ubrogepant in a population in which the majority of patients have chronic migraine, multiple prior unsuccessful treatments, complex medical comorbidities, and concurrent use of other migraine-specific medications.

Method: This was a post-market cohort study conducted at Mayo Clinic Arizona. All patients prescribed ubrogepant were tracked and contacted 1–3 months after the prescription to answer a list of standardized questions. Demographic information and additional headache history were obtained from chart review.

Results: We obtained eligible questionnaire responses from 106 patients. Chronic migraine accounted for 92/106 (86.8%) of the population. Complete headache freedom (from mild/moderate/severe to no pain) and headache relief (from moderate/severe to mild/no pain or mild to no pain) for ≥75% of all treated attacks at 2 hours after taking ubrogepant were achieved in 20/105 (19.0%) and 50/105 (47.6%) patients, respectively. A total of 33/106 (31.1%) patients reported being "very satisfied" with ubrogepant. Adverse events were reported in 42/106 (39.6%) patients, including fatigue in 29/106 (27.4%), dry mouth in 8/106 (7.5%), nausea/vomiting in 7/106 (6.6%), constipation in 5/106 (4.7%), dizziness in 3/106 (2.8%), and other adverse events in 7/106 (6.6%). Predictive factors for being a "good responder" to ubrogepant, defined as headache relief for ≥75% of all treated attacks at 2 hours after taking ubrogepant, included migraine with aura, episodic migraine, <5 prior unsuccessful preventive or acute treatment trials. Additionally, prior treatment responses to a CGRP monoclonal antibody and onabotulinumtoxinA injections are predictive of treatment responses and patient satisfaction to ubrogepant. For the 62/106 (58.5%) patients concurrently using a CGRP monoclonal antibody, there was no difference in the "good responder" rate or adverse event rate compared to those who were not on a CGRP monoclonal antibody, though the rate of moderate, as opposed to mild adverse events was higher, 11/62 (47.8%) versus 3/44 (17.6%), p = 0.048. Additionally, 16 patients had a history of significant cardiovascular or cerebrovascular diseases. No severe adverse events were reported in any patient.

Conclusion: Our study confirms and extends the efficacy profile and tolerability of ubrogepant in a real-world tertiary headache clinic and identifies factors that may predict efficacy. Adverse event rates were higher than reported in clinical trials. Further studies are needed to confirm these findings and to evaluate the long-term efficacy and safety of ubrogepant.


Ubrogepant is an oral, small-molecule calcitonin-gene-related peptide (CGRP) receptor antagonist that was approved by the food and drug administration (FDA) on December 23, 2019 for the acute treatment of migraine with or without aura in adults. This was the first in class of oral CGRP antagonist approved for the acute treatment of migraine. The efficacy and tolerability of ubrogepant were established from several clinical studies including the ACHIEVE-I and ACHIEVE-II.[1,2] It is available in two dosages, 50 and 100 mg, and both dose strengths demonstrated significantly greater rates of pain freedom and freedom from the most bothersome migraine-associated symptom at 2 hours, compared with placebo. In the clinical trials, the most commonly reported adverse events were nausea (1.7%–4.1%), somnolence (0.6%–2.1%), dry mouth (0.6%–2.1%), and dizziness (1.4%–2.1%).[1,2]

Although the efficacy, safety profile, and side effects of ubrogepant have been established in clinical trials, several limitations exist. In the ACHIEVE-1 and ACHIEVE-II trials, patients were excluded if they had 15 or more headache days per month, using acute headache medications for more than 10 days per month, were concurrently using a CGRP monoclonal antibody (mAb), or if they had clinically significant cardiovascular or cerebrovascular diseases.[1,2] This represents a large part of the clinical population for whom this medication is prescribed, especially in the headache clinic. We hypothesized that the efficacy and tolerability of ubrogepant in our population would be comparable to the data reported in the clinical trials.

However, no real-world patient experience studies have been published to validate the studies' 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, the CGRP mAbs and onabotulinumtoxinA.

The purpose of this study was to investigate the efficacy, safety, and tolerability of ubrogepant in the real-world patient population at a tertiary headache center utilizing a standardized questionnaire.