1. In this multicenter study involving adult patients in the United States with a history of migraine, ubrogepant was shown to be more effective than placebo in providing freedom from pain and alleviating the most bothersome symptom within two hours.
2. Doubling the dosage of ubrogepant resulted in limited efficacy benefits but a near-doubling of adverse events, highlighting the necessity of further research into optimal dosage.
Evidence Rating Level: 2 (Good)
Study Rundown: Serotonin receptor agonists (triptans) are currently the standard of care for acute migraine, but small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) have shown promise as first or second-line treatment. This study aimed to determine the efficacy, safety, and side-effect profile of oral ubrogepant, finding that the treatment group had a greater percentage of patients with freedom from pain and absence of the most bothersome symptom within 2 hours versus placebo. Patients in the treatment group were also more likely to experience pain relief and sustained pain relief compared to those in the control group. While no adverse events led to discontinuation of the trial regimen, patients who received the 50 mg dose of ubrogepant experienced a lower rate of adverse events versus placebo while patients who received the 100 mg dose experienced a slightly higher rate versus placebo. One strength of this study was its large study population that reflected prevalence in the general population, but the study was limited by its short time frame. Over a fifth of patients who underwent randomization were excluded from the efficacy analysis largely because they did not have a qualifying migraine within a 60-day period, which may have introduced some bias into the final results. In addition, data was collected after only a single attack, meaning that the effects of repeated use were not able to be inferred. Finally, comparative effectiveness was not assessed, limiting the clinical utility of the findings.
Click here to read the study in NEJM
Relevant Reading: The Emperor’s New Gepants: Are the Effects of the New Oral CGRP Antagonists Clinically Meaningful?
In-Depth [randomized controlled trial]: In this multicenter, double-blind, parallel-group trial, 1672 participants were randomly assigned in a 1:1:1 ratio to receive ubrogepant at a dose of 50-mg, ubrogepant at a dose of 100-mg, or placebo following stratification based on previous response to triptans (history of a response, history of an insufficient response, or no history). Participants were overwhelmingly white (82.5%) and women (88.2%). The study was conducted via a series of four clinic visits where patients were assessed within a week of taking an initial dose and received follow-up telephone calls 14 days after the initial dose. Safety was evaluated at Visit 4, which took place at the four-week mark. The two treatment groups were similar with regard to efficacy, with 19.2% and 21.2% of participants experiencing freedom from pain within two hours in the 50-mg and 100-mg groups, respectively, compared to 11.8% in the placebo group. The most bothersome symptom was alleviated in 38.6% of patients in the 50-mg ubrogepant group and 37.7% of patients in the 100-mg ubrogepant group, compared to only 27.8% of patients in the placebo group. The treatment groups also fared better with regards to the secondary endpoints of pain relief and sustained pain relief (all P-values ≤.002). While the 50-mg ubrogepant group experienced a slightly lower rate of adverse events within 48 hours of dosing (9.4%) versus placebo (12.8%), the percentage of patients in 100-mg ubrogepant group who experienced an adverse event was slightly higher (16.3%), with the most common complaints being nausea, somnolence, and dry mouth.
Image: PD
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