Anti-CGRP Antibodies: The First Migraine-Specific Prevention Drugs Work | Research

The takeaway

A systematic review of 32 trials confirmed that all four anti-CGRP monoclonal antibodies effectively prevent both episodic and chronic migraine.

4 out of 4 antibodies effective
Every anti-CGRP monoclonal antibody tested — eptinezumab, erenumab, fremanezumab, and galcanezumab — showed positive preventive results across multiple phase II/III trials

What the researchers found

All four monoclonal antibodies targeting the CGRP pathway — eptinezumab, erenumab, fremanezumab, and galcanezumab — showed positive results for preventing both episodic and chronic migraine across phase II and III clinical trials. This review of 32 eligible randomized controlled trials collectively demonstrated that blocking CGRP signaling is an effective preventive strategy for migraine.

The review noted that phase III trials were also underway for cluster headache prevention, though results were still pending at the time. The authors flagged the importance of monitoring cardiovascular effects of long-term CGRP blockade, since CGRP plays a role in blood vessel dilation and cardiovascular protection.

Why it matters

Before anti-CGRP antibodies, migraine prevention relied on drugs originally developed for other conditions — blood pressure medications, antidepressants, and anti-seizure drugs — none specifically designed for migraine. The CGRP pathway represented the first migraine-specific preventive target, offering a new class of treatment for the estimated 1 billion people worldwide affected by migraine. This systematic review captured a pivotal moment just as these drugs were entering clinical practice.

The numbers in context

136 records screened · 32 eligible RCTs reviewed · 4 monoclonal antibodies evaluated · Effective in episodic and chronic migraine

How the study worked

Systematic search of PubMed and ClinicalTrials.gov for randomized controlled trials investigating anti-CGRP monoclonal antibodies for migraine and cluster headache prevention. From 136 records, 32 were eligible for inclusion. The review synthesized phase II and III trial data for all four anti-CGRP antibodies.

Who was studied

Systematic review of RCTs involving patients with episodic migraine, chronic migraine, and cluster headache

What this study cannot tell us

Published in 2019 (accepted 2017), this review captures early clinical trial data and precedes much of the post-marketing real-world evidence now available. Long-term safety data — particularly cardiovascular effects of sustained CGRP blockade — was not yet available. The cluster headache data was limited to ongoing trials without results.

How to read the evidence

This is a strong-grade systematic review of 32 randomized controlled trials from PubMed and ClinicalTrials.gov, providing high-quality synthesized evidence for the efficacy of anti-CGRP antibodies in migraine prevention.

When this study was published

Published in 2019 (accepted 2017), this review captured the clinical trial evidence just as anti-CGRP antibodies were entering the market. All four drugs have since been FDA-approved, and extensive real-world data now supplements these trial results.

The bigger picture

This review documents the validation of CGRP as the first migraine-specific drug target — a milestone in headache medicine. Since publication, all four antibodies have been FDA-approved and are now widely prescribed. The CGRP story has expanded further with oral CGRP receptor antagonists (gepants) and the recognition that CGRP-targeted therapy works for both acute treatment and prevention. However, questions about long-term cardiovascular safety of blocking a vasodilatory peptide remain relevant.

Questions still open

What are the long-term cardiovascular consequences of chronically blocking CGRP, a peptide with cardioprotective functions?
Do anti-CGRP antibodies work differently in cluster headache compared to migraine?
How do the four anti-CGRP antibodies compare to each other in terms of efficacy and safety?

Common questions

What is CGRP and why does blocking it prevent migraines?

CGRP (calcitonin gene-related peptide) is a neuropeptide released during migraine attacks that causes blood vessel dilation and transmits pain signals. CGRP levels spike during migraines and drop when treatment works. Blocking CGRP with antibodies prevents these pain cascades from starting, reducing the frequency and severity of attacks.

Are these anti-CGRP drugs available now?

Yes, all four are FDA-approved: erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab (Vyepti). Three are self-administered monthly injections, while eptinezumab is given as a quarterly IV infusion. They are typically prescribed for people with frequent migraines who haven't responded well to other preventive treatments.

Read the original research

CGRP, a target for preventive therapy in migraine and cluster headache: Systematic review of clinical data.

Cephalalgia : an international journal of headache, 39(3), 374-389

View on PubMed ↗Publisher’s paper ↗

Citation

Khan, Sabrina; Olesen, Astrid; Ashina, Messoud. (2019). CGRP, a target for preventive therapy in migraine and cluster headache: Systematic review of clinical data.. Cephalalgia : an international journal of headache, 39(3), 374-389. https://doi.org/10.1177/0333102417741297