CGRP Antagonists Have Transformed Migraine Treatment — But Open Questions Remain | Research

The takeaway

CGRP-targeting drugs (both small-molecule antagonists and monoclonal antibodies) represent a transformative advance in migraine treatment with superior efficacy and tolerability, but access and unresolved clinical questions remain.

Transformative treatment advance
CGRP antagonists (gepants and mAbs) offer superior efficacy and tolerability for migraine vs traditional therapies

What the researchers found

CGRP-targeting drugs (gepants and monoclonal antibodies) offer superior efficacy and tolerability compared to traditional migraine therapies, representing a transformative treatment advance with remaining questions about optimization and access.

Why it matters

CGRP drugs have transformed migraine care for millions, but many patients still lack access. The review highlights that both the successes and limitations of these therapies need to be understood for optimal clinical application.

The numbers in context

Review covers both small-molecule CGRP receptor antagonists (gepants) and monoclonal antibodies (4 available); examines efficacy and tolerability data.

How the study worked

Narrative review covering CGRP pathophysiology in migraine, clinical evidence for CGRP-targeted treatments, and open questions for clinical practice.

Who was studied

Review of CGRP antagonist therapy for migraine

What this study cannot tell us

Narrative review — no new data. Does not quantify specific efficacy numbers. Open questions about long-term safety, optimal switching strategies, and biomarkers for response prediction are acknowledged but not answered.

How to read the evidence

Strong evidence base — the review draws on extensive clinical trial data supporting CGRP-targeted therapies, though the review itself is narrative rather than systematic.

When this study was published

Published in 2024. Reflects the current clinical landscape for CGRP-targeted migraine therapy.

The bigger picture

CGRP-targeting drugs represent one of the most successful examples of translational neuroscience — from discovering a peptide's role in disease to developing targeted therapies within two decades. The remaining challenge is ensuring equitable access to these life-changing treatments.

Questions still open

Can biomarkers predict which patients will respond to CGRP-targeted therapy?
What is the long-term safety profile of chronic CGRP pathway suppression?
How should CGRP drugs be positioned relative to newer targets like PACAP?

Common questions

What are CGRP drugs and why are they important for migraine?

CGRP drugs target a specific peptide (calcitonin gene-related peptide) that plays a key role in causing migraines. They come as monthly injections (antibodies like Aimovig, Emgality, Ajovy) or pills (gepants like rimegepant, ubrogepant). They work better and have fewer side effects than older migraine prevention medications.

Why can't everyone with migraine get these drugs?

Access barriers include cost, insurance restrictions, and availability. Many health systems require patients to fail multiple older, cheaper medications before approving CGRP drugs. This review argues for expanded access because inadequately treated migraine causes significant disability and complications.

Read the original research

Understanding the efficacy and tolerability of migraine treatment: a deep dive into CGRP antagonists.

Expert review of clinical pharmacology, 17(11), 1039-1051

View on PubMed ↗Publisher’s paper ↗

Citation

Waliszewska-Prosół, Marta; Raffaelli, Bianca; Straburzyński, Marcin; Martelletti, Paolo. (2024). Understanding the efficacy and tolerability of migraine treatment: a deep dive into CGRP antagonists.. Expert review of clinical pharmacology, 17(11), 1039-1051. https://doi.org/10.1080/17512433.2024.2417655