Migraine: Rimegepant as dual treatment heralds a new paradigm
09 Feb 2025
Rimegepant, an oral calcitonin gene–related peptide (CGRP)–targeted therapy indicated for both acute and preventive treatment of migraine, heralds a new paradigm in long-term management of the condition.
New paradigm
“We can now tear down the wall between acute and preventive treatment of migraine because rimegepant works both acutely and preventively,” said Professor Steward J. Tepper of Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, US, at the 37th Annual Scientific Meeting of the Hong Kong Neurological Society (HKNS 2024). “The new paradigm is to treat migraine early with gepants, during the prodrome or mild pain phase, and anticipate both acute and preventive effects. For prevention, use migraine-specific CGRP-targeted therapy.” [Lancet 2019;394:737-745; Lancet Neurol 2023;22:476-484; Lancet 2023;402:2307-2316; J Headache Pain 2022;23:10; Lancet 2021;397:51-60; Cephalalgia 2024;44:3331024241232944]
Rimegepant’s efficacy, safety and tolerability
Across pivotal phase III trials of rimegepant (75 mg QD PRN) vs placebo for acute treatment of migraine in the US and Asia (China and South Korea), freedom from pain at 2 hours postdose was achieved in 20–21 vs 11 percent of patients in the rimegepant vs placebo group (p<0.0001). “At 1 hour postdose, restoration of normal function was achieved in 22.3 vs 15.8 percent of patients [in the US trial],” Tepper pointed out. [Lancet 2019;394:737-745; Lancet Neurol 2023;22:476-484]
“In these pivotal trials, patients were instructed to wait until they experienced moderate-to-severe pain before taking the assigned treatment,” added Tepper. [Lancet 2019;394:737-745; Lancet Neurol 2023;22:476-484] “In clinical practice, patients should be advised to take gepants early, as recent evidence demonstrates their effectiveness when taken in the prodrome phase.” [Lancet 2023;402:2307-2316]
Long-term use of rimegepant in acute treatment of migraine has also demonstrated a preventive effect. Among patients who took rimegepant (75 mg QD PRN) for acute treatment of migraine for up to 52 weeks in an open-label safety study, overall mean monthly migraine days (MMDs) decreased from 10.9 days at baseline to 8.9 days by week 52, and no evidence of medication overuse headache (MOH) was found. [J Headache Pain 2022;23:10]
In the pivotal phase II/III trial on migraine prevention among patients with a mean of 10 MMDs at baseline, rimegepant (75 mg every other day) reduced mean MMDs by 4.3 days during weeks 9–12 (vs -3.5 days in the placebo group; p=0.0099). [Lancet 2021;397:51-60] “MMDs dropped further with continued rimegepant treatment during the subsequent open-label extension period in months 4–16. The overall mean reduction in MMDs from baseline was 6.2 days over the 16-month period, indicating effective prophylaxis with rimegepant,” said Tepper. [Rimegepant Hong Kong Prescribing Information, June 2023]
Rimegepant’s safety and tolerability profile was similar to that of placebo in the pivotal trials. [Lancet 2019;394:737-745; Lancet Neurol 2023;22:476-484; Lancet 2021;397:51-60]
In the 52-week open-label safety study, most adverse events were mild or moderate and considered unrelated to rimegepant. With a mean rimegepant exposure of 7.7 tablets per month (range, 5.6–13.7) for up to 52 weeks across the PRN and PRN + every-other-day dosing groups, no signal of MOH or hepatotoxicity was identified. [Cephalalgia 2024;44:3331024241232944] In contrast, triptans and combination analgesics may contribute to MOH if used regularly on ≥10 days per month for >3 months, while regular use of NSAIDs or simple analgesics on ≥15 days per month for >3 months may also contribute to MOH. [Cephalalgia 2018;38:1-211]
2024 international recommendations
“Gepants are now recommended as first-line therapies for migraine in multiple position statements worldwide,” said Tepper.
The American Headache Society recommends CGRP-targeting therapies, including gepants, as a first-line option for preventive treatment of migraine. [Headache 2024;64:333-341] Gepants are also recommended by Polish experts as a first-line option for acute treatment of moderate and severe migraine attacks as well as for preventive treatment of migraine, and are included in United Arab Emirates’ expert consensus statements as one of the options for acute treatment of migraine. [Arch Med Sci 2024;20:339-343; Neurol Ther 2024;13:257-281]