Patients treated with rimegepant appear to have more migraine-free days.The CGRP* receptor antagonist rimegepant provides consistent pain relief and improves function in patients with migraine, as shown in the CONFIDENCE trial presented at EAN 2026.
Rimegepant resulted in higher odds of migraine-free days compared with other medications for acute migraine. Among all rimegepant-treated attacks, 61 percent achieved significant pain relief, 58 percent achieved meaningful improvement in function within 2 hours of treatment, and 68 percent reported treatment satisfaction.
CONFIDENCE (NCT06467370) evaluated rimegepant as an acute treatment for migraine in a real-world setting. Researchers led by Dr Richard Lipton from the Albert Einstein College of Medicine in New York City, New York, US sought to determine the consistency of response to rimegepant across multiple attacks and among those taking concomitant preventive medications for migraine, including monoclonal antibodies and onabotulinumtoxinA. [EAN 2026, abstract EPO-0581]
Participants completed a 28-day migraine diary. Preventive therapy was permitted.
All acutely treated migraine attacks were recorded three days before the end of the study and before the next attack. Generalized linear mixed models with a logit link were used to calculate the odds ratios for ≥1, ≥2, ≥3, or ≥4 consecutive migraine-free days following rimegepant treatment compared with other medications.
Migraine-freedom achieved
The study enrolled 416 participants and recorded data on 2,169 rimegepant-treated attacks. Regardless of the acute treatment used, 64.9 percent of attacks were followed by ≥1, 47.6 percent by ≥2, 35.4 percent by ≥3, and 25 percent by ≥4 migraine-free days.
In models evaluating treatment alone, rimegepant was associated with a significantly higher likelihood of achieving migraine freedom on ≥1 (77 percent), ≥2 (71 percent), ≥3 (58 percent), and ≥4 days (44 percent) compared with other medications for acute migraine.
In models controlling for migraine days, pain level, and functional ability at the time of treatment, rimegepant was associated with a significantly higher likelihood of achieving migraine freedom on ≥1 (54 percent), ≥2 (48 percent), and ≥3 days (30 percent) than with other medications.
Migraine tracking via app
One distinctive feature of the CONFIDENCE study is that it utilized the Migraine Buddy app, which, according to Lipton, is widely used worldwide.
“We provided customized questions at baseline and diaries via the app for a month to gather information on how people who had been prescribed rimegepant responded to treatment,” he said. “This is a new way of collecting real-world evidence on treatments.”
The second aspect emphasizes the significance of keeping treatment consistent. “In typical clinical trials of migraine, we assess the benefit of an active treatment compared with placebo in individuals experiencing a single attack. However, in the real world, migraine is a recurrent condition, and many patients treat multiple attacks over time with effective medications,” noted Lipton.
Migraine relief within 2 hrs
Researchers enrolled individuals with 3 to 14 headache days in the past 30 days, who had a rimegepant prescription and planned to use it throughout the study.
The objective of the study was to assess the consistency of response to rimegepant across multiple attacks. “The study endpoints included pain relief within 2 or 4 hours of treatment, and the proportion of people who had meaningful improvement in function within 2 or 4 hours. We also looked at a measure of satisfaction,” said Lipton.
“In this real-world context, rimegepant showed high efficacy within 2 hours. When we assessed consistency, defined as the proportion of individuals who treated at least three attacks and achieved a good outcome in at least two of their first three recorded attacks, 65 percent had consistent 2-hour relief, and 60 percent had consistent and meaningful improvement in function,” he continued.
“Based on this information, we conclude that rimegepant provides consistent, meaningful pain relief and functional improvement across multiple attacks in a real-world setting,” Lipton said.
Meta-analysis supports rimegepant efficacy
A separate meta-analysis of three randomized controlled trials evaluating rimegepant 75 mg vs placebo for migraine showed rapid and sustained reduction in migraine days, with significant functional improvement. [EAN 2026, abstract EPV-0536]
Rimegepant significantly reduced monthly migraine days during the first 4 weeks of treatment (mean difference [MD], -1.59), the entire double-blind treatment phase (MD, -1.31), and the last 4 weeks of treatment (MD, -1.15).
Functional recovery improved significantly at week 12 (migraine-specific quality-of-life MD, +4.35).
The risk of any adverse events (AEs) and of AEs leading to discontinuation did not differ significantly from placebo.
“Rimegepant’s efficacy within 4 weeks and its placebo-like safety profile established it as a highly effective, well-tolerated oral preventive therapy, significantly enhancing patient quality of life,” said the researchers.