Combining oral rimegepant (a gepant) for acute migraine with injectable CGRP antibodies for prevention was well tolerated in 13 patients with no serious safety concerns over about 10 weeks.
Zero serious adverse eventsAcross 224 doses of rimegepant in 13 patients simultaneously taking CGRP antibodies, there were no serious adverse events, no treatment discontinuations, and no liver enzyme elevations — initial reassurance for dual CGRP blockade.
What the researchers found
Combining the oral CGRP receptor antagonist rimegepant (75 mg as needed) with injectable CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) for migraine was well tolerated in 13 patients over approximately 10 weeks. A total of 224 rimegepant doses were taken. Five patients (38%) reported mild adverse events, most commonly nasopharyngitis. Three patients had mild-to-moderate events considered potentially treatment-related. No serious adverse events, no treatment discontinuations, and no liver enzyme elevations occurred. This provides the first systematic safety data for using two different CGRP-targeting therapies simultaneously.
Why it matters
Many migraine patients use a CGRP antibody injection monthly for prevention but still need acute treatment when breakthrough attacks occur. Using a gepant (like rimegepant) for these attacks means both the preventive and acute treatments block the same CGRP pathway, raising theoretical safety concerns about "double CGRP blockade." This study provides reassurance that the combination appears safe — an important practical finding because it validates a treatment approach clinicians are already using in practice.
The numbers in context
n=13 · 224 total rimegepant doses · Mean 7.8 doses per 4 weeks · 9.6 weeks mean treatment · 38% had ≥1 AE · 15% nasopharyngitis · 0 serious AEs · 0 discontinuations · 0 liver enzyme elevations >3× ULN
How the study worked
This was a substudy nested within a larger multicenter, open-label, long-term rimegepant safety study. Thirteen patients with 2-8 monthly migraine attacks who were already on stable CGRP mAb therapy (erenumab n=7, fremanezumab n=4, galcanezumab n=2) took rimegepant 75 mg as needed (up to once daily) for acute treatment over 12 weeks. Safety was assessed through adverse event monitoring and liver enzyme testing.
Who was studied
13 adults with migraine (11 women, mean age 49.9) already taking CGRP monoclonal antibodies who added rimegepant for acute treatment
What this study cannot tell us
The sample size of 13 is very small — too small to detect rare safety signals. The study is open-label with no control group. The 12-week duration may not capture long-term safety concerns. The study cannot assess whether dual CGRP blockade reduces efficacy of either drug. The highly selected patient population (stable on CGRP mAb, moderate attack frequency) may not represent all patients who would use this combination in practice.
How to read the evidence
This is a very small (n=13), open-label substudy without a control group. While the absence of serious adverse events is reassuring, the sample size is insufficient to detect rare safety signals. It provides preliminary evidence only, with the authors explicitly calling for larger confirmatory studies.
When this study was published
Published in 2020, shortly after both gepants and CGRP antibodies became widely available. Since then, larger observational studies and real-world data have further supported the safety of this combination, making these early findings validated by subsequent evidence.
The bigger picture
The approval of both CGRP antibodies (for prevention) and gepants (for acute treatment) created an obvious clinical question: can patients use both? Both drug types target the CGRP pathway but through different mechanisms — antibodies block the peptide or receptor for weeks, while gepants provide short-term receptor blockade. This study is one of the first to formally assess the combination, and the reassuring safety data supports what many headache specialists were already doing in practice. Larger studies have since been conducted to confirm these preliminary findings.
Questions still open
- Does dual CGRP blockade reduce the acute efficacy of rimegepant, since the CGRP pathway is already partially blocked by the antibody?
- Are there specific CGRP antibody-gepant combinations that are safer or more effective than others?
- What are the long-term effects of sustained dual CGRP pathway blockade on cardiovascular function, wound healing, or other CGRP-dependent processes?
Common questions
Can I use rimegepant if I'm already on a CGRP antibody for migraine?
Doesn't blocking CGRP twice cause problems?
Read the original research
Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine.
Headache, 60(8), 1734-1742
Citation
Berman, Gary; Croop, Robert; Kudrow, David; Halverson, Philip; Lovegren, Meghan; Thiry, Alexandra C; Conway, Charles M; Coric, Vladimir; Lipton, Richard B. (2020). Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine.. Headache, 60(8), 1734-1742. https://doi.org/10.1111/head.13930