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How CGRP-Targeted Therapies Are Changing Migraine Treatment — and the Challenges That Remain

ReviewModerate evidence
The takeaway

CGRP-targeted therapies (monoclonal antibodies and gepants) have transformed migraine treatment by targeting its underlying biology, but access barriers, high costs, and limited long-term data remain significant challenges.

14.1% of the global population

Migraine is one of the most common neurological conditions worldwide, disproportionately affecting women, and CGRP-targeted therapies are the first treatments designed specifically for its underlying biology.

What the researchers found

This comprehensive review examines the paradigm shift in migraine treatment driven by therapies targeting calcitonin gene-related peptide (CGRP) — a neuropeptide central to migraine pathophysiology. CGRP monoclonal antibodies (for prevention) and gepants (small molecule CGRP receptor antagonists, for both acute and preventive use) have demonstrated strong efficacy and tolerability in clinical trials. The review highlights that despite these advances, significant barriers persist: misdiagnosis, medication overuse headaches, high costs, limited long-term safety data, and restricted access to specialist care, particularly in developing countries like Turkiye.

Why it matters

Migraine affects 14.1% of the world's population and has historically been undertreated and misunderstood. For decades, migraine treatments were borrowed from other conditions — blood pressure drugs, antidepressants, anti-seizure medications. CGRP-targeted therapies represent the first class of treatments designed specifically for migraine based on its underlying biology. This review contextualizes how these peptide-based treatments have transformed the field while honestly addressing the barriers to global access.

The numbers in context

14.1% global prevalence of migraine

How the study worked

This is a narrative review examining migraine pathophysiology, the role of CGRP in trigeminovascular activation, clinical trial data for CGRP monoclonal antibodies and gepants, pharmacokinetic and pharmacodynamic profiles, safety and tolerability data, and real-world treatment barriers. The authors provide strategic recommendations for improving migraine care, with particular focus on Turkiye and developing nations.

Who was studied

Not applicable — review article covering the global migraine population, with specific focus on treatment access in Turkiye and developing countries

What this study cannot tell us

As a narrative review, this article does not employ systematic review methodology or meta-analysis. The strategic recommendations are specifically tailored to Turkiye and developing countries, which may limit direct applicability to other healthcare systems. The review acknowledges the limited availability of long-term efficacy data for CGRP-targeted therapies.

How to read the evidence

This is a narrative review synthesizing evidence from clinical trials and pharmacological studies. While it covers robust clinical trial data, the review itself does not perform independent analysis, and some recommendations are consensus-based rather than data-driven.

When this study was published

Published in 2024, this review captures the current state of CGRP-targeted therapy development, including the latest clinical evidence and real-world implementation challenges. It is up-to-date and clinically relevant.

The bigger picture

The CGRP story is one of the most successful examples of translational neuroscience — decades of basic research on a single neuropeptide ultimately produced an entirely new class of therapies. Before CGRP-targeted drugs, the last major migraine-specific treatment class was the triptans, introduced in the 1990s. The development of anti-CGRP therapies has also deepened scientific understanding of the trigeminovascular system and opened the door to targeting other neuropeptides involved in headache disorders.

Questions still open

  • What are the long-term safety and efficacy profiles of CGRP monoclonal antibodies and gepants when used for years or decades?
  • How can access to CGRP-targeted therapies be improved in developing countries where cost and specialist shortages are major barriers?
  • Are there patients who respond to one type of CGRP-targeted therapy (antibodies vs. gepants) but not the other, and what determines this?

Common questions

What is CGRP and why does it matter for migraines?
CGRP (calcitonin gene-related peptide) is a neuropeptide released by nerve fibers in the trigeminovascular system during a migraine attack. It causes blood vessel dilation and inflammation in the brain's protective coverings, contributing to migraine pain. Drugs that block CGRP or its receptor can prevent or treat migraines by interrupting this process.
What's the difference between CGRP antibodies and gepants?
CGRP monoclonal antibodies are injectable medications given monthly or quarterly that block the CGRP molecule or its receptor for prevention. Gepants are oral small-molecule drugs that block the CGRP receptor and can be used both for acute treatment of individual attacks and for daily prevention.

Read the original research

Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.

Frontiers in neurology, 15, 1402569

Citation

Özge, A; Baykan, B; Bıçakçı, Ş; Ertaş, M; Atalar, A Ç; Gümrü, S; Karlı, N. (2024). Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.. Frontiers in neurology, 15, 1402569. https://doi.org/10.3389/fneur.2024.1402569