Definition and Overview
CGRP inhibitors (calcitonin gene-related peptide inhibitors) are a drug class that targets the CGRP signaling pathway, a core pathophysiological mechanism of migraine. CGRP is a potent vasodilatory neuropeptide released from trigeminal nerve terminals, with plasma levels surging during migraine attacks and playing a central role in headache generation.
Erenumab received US FDA approval in 2018, marking the clinical introduction of the first preventive drug class specifically designed for migraine. CGRP inhibitors are broadly divided into monoclonal antibodies (mAbs) and small-molecule gepants.
Etiology and Pathophysiology
During migraine attacks, CGRP is massively released from the trigeminal ganglion and the trigeminovascular complex. CGRP induces meningeal vasodilation, neurogenic inflammation, and central sensitization, resulting in headache, allodynia, and cutaneous sensitivity. CGRP inhibitors prevent migraine and relieve acute symptoms by blocking this pathway.
Symptoms
As CGRP inhibitors are therapeutic agents, there is no specific symptom classification, but understanding the characteristics of their target condition -- migraine -- is important.
Migraine is a primary headache disorder characterized by moderate-to-severe pulsating headache lasting 4 to 72 hours, accompanied by nausea/vomiting, photophobia, and phonophobia. Chronic migraine is defined as headache on 15 or more days per month (with at least 8 days having migraine features).
Diagnosis
Indications for CGRP inhibitors are determined after establishing a migraine diagnosis according to the International Classification of Headache Disorders (ICHD-3) criteria.
- Episodic migraine: 4 or more monthly headache days, after inadequate response or adverse effects from 1-2 or more prior preventive medications
- Chronic migraine: headache on 15 or more days per month, after failure of 2 or more prior preventive medications
Treatment
Monoclonal Antibodies (Preventive Treatment)
| Drug | Target | Route | Frequency |
|------|--------|-------|-----------|
| Erenumab | CGRP receptor | Subcutaneous injection | Monthly |
| Galcanezumab | CGRP ligand | Subcutaneous injection | Monthly |
| Fremanezumab | CGRP ligand | Subcutaneous injection | Monthly or quarterly |
| Eptinezumab | CGRP ligand | Intravenous infusion | Quarterly |
Clinical trials demonstrated that monoclonal antibodies reduced monthly headache days by approximately 3.7 to 6.6 days compared to placebo [1][2], with 50% or greater headache reduction response rates of approximately 40-60% [2][4].
Gepants (Small-Molecule CGRP Receptor Antagonists)
- Ubrogepant: oral acute treatment
- Rimegepant: approved for both acute and preventive use
- Atogepant: oral preventive treatment
Unlike triptans, gepants lack vasoconstrictive properties and can be used relatively safely in patients with cardiovascular disease history.
Lasmiditan (Serotonin Receptor Agonist)
Lasmiditan is not a CGRP inhibitor but was introduced in a similar era as an acute migraine treatment that selectively targets the 5-HT1F receptor. Lacking vasoconstrictive effects, it serves as an alternative for patients in whom triptans are contraindicated.
Prognosis
CGRP monoclonal antibodies generally have favorable long-term tolerability. Treatment response is evaluated after a minimum of 3 months of therapy. Approximately one-third of patients respond within 1 to 3 months of treatment initiation, while some require longer periods. Efficacy has been demonstrated even in patients who failed multiple prior preventive medications, making these agents an important option for refractory migraine management.
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This information is provided for medical educational purposes only and does not replace professional medical advice.
If you are experiencing symptoms, please consult a specialist.
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