This was the first study to demonstrate a preventive treatment signal in migraine when an approved oral CGRP receptor antagonist is dosed as needed for the acute treatment of migraine.
Rimegepant (Nurtec ODT; Biohaven Pharmaceuticals), an FDA-approved calcitonin gene-related peptide (CGRP) receptor antagonist, was shown to provide effective acute treatment of migraine over a 52-week period in patients presenting with more than 6 monthly migraine days (MMD) per month.1
The data stems from the phase 2/3 open-label safety study BHV3000-201 (NCT03266588), which included 1044 patients who self-administered 75-mg rimegepant orally as needed (PRN) to acutely treat their migraine. This was the first study to utilize Kaplan-Meier and Cox proportional hazards methodology to describe longitudinal changes in migraine frequency.
"The Kaplan-Meier methodology provides for a novel assessment of migraine treatment efficacy and enables the ability to estimate adjusted hazard ratios for time to these outcomes (ie, via Cox regression),” primary investigator Gil L’Italien, PhD, senior vice president, GHEOR & Epidemiology, Biohaven, said in a statement. "These observations of migraine frequency reduction from repeated effective acute rimegepant treatment show reductions in migraine days after repeated acute therapy and are consistent with Nurtec ODT's known preventive effects."1
Of the 1044 participants with 6 or more MMD at baseline, 635 (61%) completed the study while 409 (39%) discontinued treatment. The primary outcome measures for the post-hoc analysis were median time to at least 30% and 50% reduction in MMDs, assessed at 4-week intervals from baseline up to 52-weeks.2
The reduction in MMD frequency over time in rimegepant-treated patients was significant regardless of baseline migraine frequency, including those with low-frequency (baseline MMD, 8.7), moderate frequency (baseline MMD, 11.5) and high-frequency (baseline MMD, 14.8) cluster groups. The median time to at least a 30% reduction of baseline MMDs was 12 weeks (IQR, 4-40), while the median time to at least a 50% reduction was 32 weeks (IQR, 12-NR). At the 52-week mark, 78.6% of participants achieved at least a 30% reduction of baseline MMDs and 63.3% of participants showed at least a 50% reduction.
Across the different migraine frequency cluster groups, MMD reduction trends were nonlinear, tended to show more initial rapid decline, and were followed by a smaller more incremental reduction for the remainder of the follow-up period. Furthermore, higher baseline monthly migraine frequency was found to be associated with a reduced rate of achieving at least a 30% or 50% reduction in MMD.
Using Cox proportional hazards models that adjusted for age and sex, the highest MMD group compared to the lowest had HRs of 5.47 (95% CI, 4.27-7.00; P > .05) and 5.74 (95% CI, 4.22-7.81; P >.05) for at least 30% and 50% MMD reductions, respectfully. Moderate-frequency MMD versus low-frequency MMD showed HRs of 2.13 (95% CI, 1.64-2.76; P >.05) for at least a 30% reduction and 1.91 (95% CI, 1.37-2.65; P >.05) for at least 50% reduction in MMD.
For those in the highest-frequency MMD group, median time to at least a 30% reduction was not reached, whereas those in the moderate-frequency and lowest-frequency groups achieved that mark in 20 (IQR, 8-NR) and 8 (IQR, 4-16) weeks, respectively. Likewise, the low-frequency group reached at least a 50% reduction in baseline MMDs faster than the other 2 frequency groups.
Karissa Johnston, PhD, scientific director, Broadstreet HOER, said in a statement, “The study results confirm that continued use of rimegepant as an acute treatment to help stop a migraine can also lessen the number of migraine attacks a person has over time. This is a significant added benefit that healthcare providers and patients should consider when determining the right acute treatment plan."1
In May 2021, rimegepant made history becoming the first FDA-approved oral CGRP antagonist for both acute and preventive treatment of migraine. The orally disintegrating anti-CGRP tablet was originally approved in a 75-mg dose for the acute treatment of migraine in February 2020–the first approval of a therapy for Biohaven.3
NeurologyLive® recently hosted an Insights series, led by David Kudrow, MD, that highlights the management of acute and preventative migraine. In the episode below, he discussed how the rippling effect of rimegepant’s landmark approval, as well when the medication may be most effective.
1. Nurtec ODT when taken as an acute treatment for migraine reduces monthly migraine days: expanded data from long-term treatment published in Cephalalgia reports. News release. Biohaven Pharmaceuticals. February 3, 2022. Accessed February 7, 2022. https://www.prnewswire.com/news-releases/nurtec-odt-when-taken-as-an-acute-treatment-for-migraine-reduces-monthly-migraine-days-expanded-data-from-long-term-treatment-published-in-cephalalgia-reports-301474512.html
2. L’Italien G, Popoff G, Johnston K, et al. Rimegepant 75 mg for acute treatment of migraine is associated with significant reduction in monthly migraine days: results from a long-term, open-label study. Cephalalgia Rep. Published online February 1, 2022. doi:10.1177/25158163221075596
3. FDA Approves Biohaven's NURTEC® ODT (rimegepant) for Prevention: Now the First and Only Migraine Medication for both Acute and Preventive Treatment. News release. May 27, 2021. Accessed February 7. 2022. https://www.prnewswire.com/news-releases/fda-approves-biohavens-nurtec-odt-rimegepant-for-prevention-now-the-first-and-only-migraine-medication-for-both-acute-and-preventive-treatment-301301304.html