Time Course of Rimegepant Effect for Acute Treatment of Migraine in Adults Unsuitable for Triptans: Exploratory Endpoints from a Phase 4, Randomized, Double-Blind, Placebo-Controlled Study

A recent placebo-controlled trial (NCT05509400) demonstrated efficacy of single-dose rimegepant 75 mg for acute treatment of migraine in adults unsuitable for triptans. However, the full time course of rimegepant effect has not been reported for this study population. Pre-specified exploratory endpoints from study NCT05509400 assessed the percentage of participants with migraine pain relief, migraine pain freedom, return to normal function, and most bothersome symptom (MBS; nausea, photophobia, or phonophobia) freedom from 15 min to 48 h post-dose. Treatment comparisons used crude risk estimation with nominal p values. Participants (rimegepant n = 286; placebo n = 284) were mostly female (89.3%) and had documented failure to ≥ 2 triptans with ≥ 1 reason due to prior intolerance (30.5%) or lack of efficacy (84.9%); 9.1% had a contraindication. Improvements of ≥ 5% for rimegepant over placebo with p ≤ 0.05 [difference (95% CI)] were first observed at 1 h for pain relief [8.6% (1.3%, 15.8%); p = 0.0201], 1.5 h for pain freedom [6.2% (1.5%, 11.0%); p = 0.0103] and return to normal function [7.1% (1.1%, 13.1%); p = 0.0210], and 2 h for MBS freedom [12.5% (5.4%, 19.5%); p = 0.0005]. Improvements of ≥ 5% over placebo were observed at all subsequent time points. Differences (95% CI) at 48 h were 31.2% (23.5%, 39.0%; p < 0.0001) for pain relief, 33.4% (25.9%, 40.9%; p < 0.0001) for pain freedom, 34.1% (25.8%, 42.5%; p < 0.0001) for return to normal function, and 23.2% (15.5%, 31.0%; p < 0.0001) for MBS freedom. In some patients unsuitable for triptans, rimegepant can provide rapid onset (within 1–2 h) of migraine symptom improvement. Improvements may be observed up to 48 h. Rimegepant may be appropriate when triptans are not suitable, particularly in individuals who failed triptans previously due to lack of efficacy. Graphical abstract available for this article. ClinicalTrials.gov: NCT05509400. Triptans are commonly used to stop an ongoing migraine attack. However, triptans may not be suitable for all patients since (1) triptans do not work well in some patients, (2) triptans cause side effects in some patients that makes them stop treatment, and (3) some people have conditions that increase the risk of serious side effects when using triptans (this is called a contraindication). Rimegepant is an oral (taken by mouth) medicine used to treat migraine attacks. Rimegepant works differently than triptans. This study looked at how fast rimegepant improves migraine symptoms in people who are not suitable for triptans. Patients treated 1 migraine attack of moderate or severe headache pain intensity with a single dose of rimegepant (n = 286) or placebo (n = 284). Patients rated migraine symptoms before, and up to 48 h after, taking rimegepant or placebo. At each time point, researchers looked at the percentage of patients who had pain relief (having no or only mild headache pain), pain freedom (having no headache pain), return to normal function, and freedom from their most bothersome symptom (either feeling sick to their stomach, sensitivity to light, or sensitivity to sound; chosen before taking rimegepant or placebo). Compared to placebo, rimegepant provided meaningful improvements in pain relief, pain freedom, return to normal function, and freedom from the most bothersome symptom within 1–2 h. These improvements were observed through 48 h. These results suggest that rimegepant may be a useful treatment for migraine in people who are unsuitable for triptans, particularly in individuals who failed triptans previously due to lack of efficacy. Graphical abstract available for this article.