Objective:

To quantify longitudinal changes in headache outcomes in subjects initiating rimegepant for migraine prevention.

Background:

While trials support rimegepant’s efficacy, real-world data on sustained preventive outcomes remain limited. Evaluating treatment effects across multiple time intervals is essential to understanding rimegepant’s long-term effectiveness.

Design/Methods:

Using EMR data with structured outcome forms collected during each visit, we analyzed longitudinal outcomes from subjects initiating preventive rimegepant at the Jefferson Headache Center (11/2020-7/2025). Subjects with only acute rimegepant use were excluded. The assessed duration encompassed all rimegepant exposure with assessable outcomes. Four datasets were constructed with follow-up capped at 3, 6, 12, or 24 months. Linear mixed-effects models (no imputation) with random intercepts estimated slopes for monthly headache days (MHD), moderate/severe headache days (MSD), worst pain intensity (WPI), average pain intensity (API), acute medication use days (AMD), and Migraine Disability Assessment (MIDAS) score. Models adjusted for sex, age, BMI, and concurrent onabotulinumtoxinA exposure.

Results:

Across 451 eligible subjects (age 45.3±14.8, female 83.6%, BMI 27.6±6.4), rimegepant use persisted in 84.3%, 66.1%, 35.7%, and 9.8% by 3, 6, 12, and 24 months. MHD declined at 3 months (–0.77 days/month, p=0.009), with smaller slopes at 6 (–0.46, p<0.001), 12 (–0.26, p<0.001), and 24 months (–0.11, p=0.007). MSD improved at 6 (–0.40, p=0.02) and 12 months (–0.25, p=0.003) before plateauing. WPI improved at 3 months (–0.17, p=0.003) and remained reduced. API improved only at 3 months (–0.23, p<0.001). AMD showed no significant change. MIDAS scores improved from 6 months onward (–2.3, p=0.04; –1.2, p=0.02; –1.0, p=0.0003).

Conclusions:

Preventive rimegepant was associated with early reductions in MHD, WPI, and API, while MSD and MIDAS improvements emerged later. These findings provide real-world data of early symptomatic benefit and evolving functional gains with rimegepant. Observed improvements reflect while-on-treatment outcomes; high discontinuation limits inference on sustained benefit.