Definition and Overview
CGRP inhibitors (calcitonin gene-related peptide inhibitors) are a group of drugs that target the CGRP signaling pathway, a key pathophysiological mechanism of migraine. CGRP (calcitonin gene-related peptide) is a powerful vasodilator neuropeptide secreted from the terminal of the trigeminal nerve. Its blood concentration rapidly increases during a migraine attack and plays a key role in the occurrence of headaches.
In 2018, erenumab was introduced into clinical trials after receiving approval from the US FDA, and is the first preventive drug specifically designed for migraine. It is largely divided into monoclonal antibodies (mAb) and small molecule gepants.
Causes and Pathophysiology
During a migraine attack, large amounts of CGRP are released from the trigeminal ganglion and trigeminovascular complex. CGRP causes meningeal vasodilation, neurogenic inflammation, and central sensitization, resulting in headache, numbness, and allodynia. CGRP inhibitors prevent migraines and relieve acute symptoms by blocking this pathway.
symptoms
Since CGRP inhibitors are treatments, there is no separate symptom classification, but it is important to understand the characteristics of migraine, the disease to which it is applied.
Migraine is a primary headache disorder characterized by moderate to severe pulsating headaches lasting 4 to 72 hours and accompanied by nausea/vomiting, photophobia, and phonophobia. Chronic migraine is a condition in which headaches persist for more than 15 days a month (of which 8 or more days are migraine-like).
diagnosis
The indication for CGRP inhibitors is determined after establishing a diagnosis of migraine (International Classification of Headache Disorders, ICHD-3 criteria).
- Episodic migraine: When there are more than 4 headache days per month and the effect is insufficient or side effects occur after trying 1-2 or more existing preventive drugs.
- Chronic migraine: headache more than 15 days a month, after failure of two or more existing preventive medications
treatment
Monoclonal antibodies (preventive treatment)
| medication | target | Method of administration | frequency | |------|------|-------|------| | erenumab | CGRP receptor | subcutaneous injection | Once a month | | galcanezumab | CGRP Ligand | subcutaneous injection | Once a month | | fremanezumab | CGRP Ligand | subcutaneous injection | Once a month or once a quarter | | eptinezumab | CGRP Ligand | Intravenous Injection | Once a quarter |
In clinical studies, when monoclonal antibodies were administered, the number of monthly headache days was reduced by about 3.7 to 6.6 days compared to placebo, and the response rate for headache reduction by more than 50% was about 40 to 60%.
Gepant (small molecule CGRP receptor antagonist)
- Ubrogepant: Acute oral treatment
- Rimegepant: Can be used for both acute and prophylactic purposes.
- Atogepant: Oral preventive treatment
Unlike triptans, gepants do not have a vasoconstrictive effect, so they can be used relatively safely even in patients with a history of cardiovascular disease.
Lasmiditan (serotonin receptor agonist)
Lasmiditan is not a CGRP inhibitor, but is a treatment for the acute phase of migraine that was introduced around the same time and acts selectively on the 5-HT1F receptor. It has no vasoconstrictive effect, so it is an alternative in patients contraindicated with triptan.
prognosis
CGRP monoclonal antibody is well tolerated even when used for a long period of time. After starting treatment, response evaluation is performed after at least 3 months of administration. Approximately one-third of patients respond within 1 to 3 months of treatment, although some patients require a longer period of time. Its effectiveness was confirmed even in patients who did not respond to many existing preventive drugs, making it an important option for treating intractable migraines.
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This information is provided for medical educational purposes and is not a substitute for individual medical care or treatment. If you have any symptoms, be sure to seek professional advice. Inquiries: Osang Neurosurgery 1599-5453 | osns.co.kr