Study design: This was a post-hoc analysis a multicenter, long-term, open-label phase 2/3 safety study of rimegepant 75 mg oral tablet in the acute treatment of migraine (BHV3000-201, NCT03266588).33,34 The study was conducted at 98 sites across the US between August 30, 2017 and July 15, 2019.33
Population: Eligible subjects for this post-hoc analysis were a subset of the BHV3000-201 trial, which included adults with a minimum migraine history of one-year year as classified by the International Classification of Headache Disorders, 3rd edition, beta version (ICHD-3 beta), and with ≥6 MMD at baseline.35 The ≥6 MMD subgroup was selected as these patients were hypothesized to experience a preventative benefit of rimegepant with PRN dosing (in terms of reduced MMD), given the interictal carryover of CGRP antagonism between attacks.
Intervention: Subjects of this post-hoc analysis treated migraine attacks of any pain intensity with rimegepant 75 mg oral tablet up to once daily as-needed (PRN), for up to 52 weeks.33,34
Outcome Measures: The outcome measures of interest for this post-hoc analysis were MMD frequency, the mean monthly number of rimegepant tablets taken, the cumulative pain hours, and impact of migraine on HRQoL. Mean MMD and mean tablet utilization were calculated at each 4-week period. HRQoL over time was characterized by the Migraine-specific quality of life (MSQv2) instrument, which was collected at baseline and weeks 12, 24, 36, and 52.
Cumulative pain hours
Cumulative hours of moderate and severe pain, and health-related quality of life (HRQoL) were estimated for patients receiving rimegepant based on BHV3000-201 MMD outcomes and reported HRQoL outcomes and compared to hypothetical outcomes based on baseline clinical status persisting over 52 weeks.
For hours of moderate and severe pain over time, assumed pain trajectories were applied to the MMD values observed over the 52-week follow-up. Pain freedom and relief per migraine event were derived from a network meta-analyses (NMA) conducted by the Institute for Clinical and Evaluative Review (ICER), which compared the proportion of patients experiencing headache relief and pain freedom at 2, 8, 24 and 48 hours after treatment with rimegepant or usual care (amongst others).32 Pain relief was defined as a decrease in headache pain from moderate tor severe at baseline to mild or no pain at a given follow-up time point (e.g., 2-hours) and pain freedom was achieved when a patient was completely pain-free at a given follow-up time point (e.g., 2-hours), before the use of rescue medication.32
Clinical trial data were used to calculate the proportion of patients by pain severity (no pain, mild, moderate, severe) at baseline, 2, 8, 24 and 48 hours.32 Baseline proportions of patients with moderate or severe pain in clinical trials were used as the proportion of patients with migraine, while patients who experienced no pain over a 48-hour cycle were classified as patients without migraine.32 Responses to treatment included no improvement in pain severity at 2, 8, 24 and 48 hours, pain relief (improved but not completely resolved), or pain freedom (completely resolved).32 Response at 2 hours were taken from clinical trials, while responses at 8, 24, and 48 hours were estimated by applying non-disclosed risk ratios to responders, or in case of non-responders at 2 hours, by applying these risk ratio.to placebo response rates.32,36
HRQoL over time was characterized by the MSQv2 instrument, which was collected at baseline and weeks 12, 24, 36, and 52 in BV3000-201. The MSQv2 is a validated 14-question disease-specific patient-reported outcome (PRO) measure that is frequently used to measure the impact of migraine and multidimensional aspects of preventive treatments' effectiveness on HRQoL in a meaningful way.1,37 The MSQv2 has three HRQoL dimensions: Role Function-Restrictive (RR), Role Function-Preventive (RP), and Emotional Function (EF).38 The MSQv2 values were mapped to utilities based on a validated algorithm for episodic and chronic migraine,39 and the area under the curve (AUC) of utility values over time was used to calculate quality-adjusted life years (QALYs).
Trial oversight/Ethics: BHV3000-201 was conducted in accordance with Good Clinical Practice (GCP), and Good Laboratory Practice (GLP), and in compliance with the protocol approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC), the Declaration of Helsinki, and the Federal Food, Drug and Cosmetic Act and Code of Federal Regulations.40 Written informed consent was obtained from patients in accordance with IRB/IEC requirements.40