Rimegepant shows favourable safety and tolerability in long-term acute migraine treatment

Rimegepant, taken for up to 1 year for acute treatment of migraine, is well tolerated with no signal of hepatotoxicity, a recent study has shown.

The multicentre open-label study evaluated long-term safety and tolerability of rimegepant in 1,800 adult patients with ≥1 year’s history of migraine (mean age, 43.1 years; female, 89.4 percent; mean number of moderate-to-severe migraine attacks, 6.7 per month). [Cephalalgia 2024;44:1-11]

The participants were enrolled into three groups. The first two groups were those with 2–8 or 9–14 moderate-to-severe migraine attacks per month, who were treated for 52 weeks with as-needed (pro re nata [PRN]) rimegepant 75 mg up to once daily (PRN 2–8 group, n=1,033; PRN 9–14 group, n=481). The third group comprised participants with 4–14 moderate-to-severe migraine attacks per month, who were treated for 12 weeks with rimegepant 75 mg every other day (QOD) as scheduled plus a PRN dose for migraine attacks of any severity on nonscheduled dosing days (QOD + PRN group, n=286).

The mean number of rimegepant tablets taken per month was 7.7 in the overall study population, 5.6 in the PRN 2–8 group, 8.5 in the PRN 9–14 group, and 13.7 in the QOD + PRN group.

While 60.4 percent of participants experienced ≥1 on-treatment adverse event (AE), most (78.2 percent) of the AEs were mild or moderate, and few (20 percent) were judged by investigators to be related to rimegepant. AEs led to rimegepant discontinuation in 2.7 percent of participants.

“The most common on-treatment AEs were upper respiratory tract infection [8.8 percent], nasopharyngitis [6.8 percent], and sinusitis [5.1 percent],” the investigators reported.

Serious AEs were reported in 2.6 percent of participants, most of which were considered by investigators to be unrelated to rimegepant. Serious AEs considered possibly or unlikely related to rimegepant were reported in 0.6 percent of participants.

No signal of hepatotoxicity was identified in the study. Hepatic-related on-treatment AEs, reported in 1.4 percent of participants, were mild or moderate in the majority of cases (99.9 percent) and led to rimegepant discontinuation in 0.3 percent of the participants. On-treatment alanine aminotransferase and/or aspartate aminotransferase elevations to >3 times the upper limit of normal were reported in approximately 1 percent of participants, none of whom were in the QOD + PRN group.

“No signal of potential drug abuse or medication-overuse headache was identified,” the investigators added.

“Rimegepant 75 mg up to once daily, in QOD + PRN dosing for 12 weeks or PRN dosing for up to 52 weeks, was well tolerated,” they concluded. “Rimegepant’s safety in this study was consistent with its favourable safety profile observed in previous research.”

A post hoc analysis of the study showed reductions in monthly migraine days (MMDs), stable tablet use and no evidence of medication overuse headache in patients with ≥6 MMDs at baseline in the PRN 2–8 and PRN 9–14 groups. [J Headache Pain 2022;23:10] Across all treatment groups, significant improvements in all domains of migraine-specific quality of life (QoL) were observed over time (p<0.001), along with MMD reductions. Migraine-specific QoL improvements were most pronounced in participants with more frequent migraine attacks at baseline and those who took rimegepant QOD + PRN. [Adv Ther 2021;38:5209-5220]