Efficacy of Ubrogepant in the Acute Treatment of Migraine With Mild Pain vs Moderate or Severe Pain

Abstract

Background and objectives: To examine the efficacy of ubrogepant in the treatment of migraine with mild vs moderate or severe pain.

Methods: This was a phase 3, open-label, dose-blinded, 52-week extension trial. Adults with migraine were randomized 1:1:1 (usual care, ubrogepant 50 mg, or ubrogepant 100 mg). Participants treated up to 8 migraine attacks of any pain intensity every 4 weeks. Efficacy outcomes (only collected for ubrogepant) included 2-hour pain freedom (2hPF), freedom from associated symptoms, and from disability. A generalized linear mixed model with binomial distribution and logit link function was used to assess the influence of baseline pain intensity on treatment outcomes in this post hoc analysis.

Results: Data for 19,291 attacks from 808 participants were included. 2hPF rates were higher for attacks treated when pain was mild vs moderate or severe: ubrogepant 50 mg (47.1% vs 23.6%; odds ratio [95% CI] 2.89 [2.57-3.24]) and ubrogepant 100 mg (55.2% vs 26.1%; 3.50 [3.12-3.92]; p < 0.0001 both doses). Rates of freedom from photophobia, phonophobia, and nausea 2 hours after treatment were also significantly higher following the treatment of mild vs moderate or severe pain (p < 0.001 all symptoms, both doses). At 2 hours, the proportion of attacks with normal function was more than double for both doses of ubrogepant (p < 0.001). The most common adverse event was upper respiratory tract infection (∼11% both doses). Serious adverse events were reported by 2% in ubrogepant 50 mg and 3% in ubrogepant 100 mg.

Discussion: Relative to treatment of attacks with moderate or severe pain, treatment with ubrogepant during mild pain resulted in significantly higher rates of freedom from pain, freedom from associated symptoms, and achieving normal function 2 hours after administration.

Trial registration information: ClinicalTrials.gov, NCT02873221.

Classification of evidence: This trial provides Class III evidence that treatment of migraine with ubrogepant when pain is mild vs moderate or severe increases the likelihood of achieving pain freedom, absence of symptoms, and normal function within 2 hours postdose.

Figure 1. Participant Enrollment and Disposition

All participants randomized to usual care were included in the safety population regardless of whether the participant used medication to treat migraine. For the ubrogepant treatment group, the safety population included all participants who received at least 1 dose of treatment. The analysis population was only defined for the ubrogepant treatment groups because efficacy measures were not collected for participants randomized to usual care. The analysis population is defined as all randomized patients who received at least 1 dose of ubrogepant and had at least 1 posttreatment efficacy assessment in this trial.

Figure 2. Pain Freedom at 2 Hours After Dose by Headache Severity Across All Treated Attacks in the (A) Overall Population and (B) Subgroup Who Treated Both Mild and Moderate or Severe Attacks (Analysis Population)

The analysis population is defined as all randomized patients who received at least 1 dose of ubrogepant and had at least 1 posttreatment efficacy assessment in this trial. Pain freedom is a reduction in headache severity from mild/moderate or severe at baseline to no headache pain. N1 is the total number of participants, and N2 is the total number of treated attacks. Responder rates, odds ratios (ORs), 95% CIs, and p values are based on a generalized linear mixed model that addresses the within-participant correlation. All available data are used in the analysis.

Figure 3. Absence of (A) Photophobia, (B) Phonophobia, and (C) Nausea at 2 Hours After Dose by Headache Severity Across All Treated Attacks (Analysis Population)

The analysis population is defined as all randomized patients who received at least 1 dose of ubrogepant and had at least 1 posttreatment efficacy assessment in this trial. Absence of symptom includes data for all treated attacks regardless of the presence/absence of the symptom before treatment for a particular attack. N1 is the total number of participants, and N2 is the total number of treated attacks. Responder rates, odds ratios (ORs), 95% CIs, and p values are based on a generalized linear mixed model that addresses the within-participant correlation. All available data are used in the analysis.

Figure 4. Normal Function at 2 Hours After Dose by Headache Severity Across All Treated Attacks in the (A) Overall Population and (B) Subgroup Who Treated Both Mild and Moderate or Severe Attacks (Analysis Population)

The analysis population is defined as all randomized patients who received at least 1 dose of ubrogepant and had at least 1 posttreatment efficacy assessment in this trial. Normal function per the Functional Disability Scale refers to a response option of 0 (no disability, able to function). N1 is the total number of participants, and N2 is the total number of treated attacks. Responder rates, odds ratios (ORs), 95% CIs, and p values are based on a generalized linear mixed model that addresses the within-participant correlation. All available data are used in the analysis.