Comparison to anti-CGRP monoclonal antibodies
Gepants and CGRP monoclonal antibodies are two different classes of medications that target the calcitonin gene-related peptide (CGRP) pathway, which is implicated in migraine pathophysiology. Although they both aim to manage migraine by targeting the CGRP pathway, there are some key differences between the two:
Mechanism of action:
Gepants are small molecule CGRP receptor antagonists. They work by binding to the CGRP receptor and blocking the interaction between CGRP and its receptor. This prevents the activation of the receptor and the subsequent cascade of biochemical events which promote the release of inflammatory mediators, dilate blood vessels and increase sensitivity of pain-sensing nerve fibres. These are thought to contribute to migraine pain and other migraine symptoms.
CGRP monoclonal antibodies, on the other hand, are large proteins that target either the CGRP ligand itself or its receptor. By binding to the CGRP ligand, they prevent it from interacting with the receptor, thus blocking the cascade signalling pathway. Alternatively, by binding to the receptor, they can prevent CGRP from activating it.
Gepants are typically administered orally as pills, making them convenient for patients to use on an as-needed basis for acute migraine treatment.
CGRP monoclonal antibodies are administered via subcutaneous injection or intravenous infusion. They are prescribed for the preventive treatment of migraine and are administered on a regular basis, such as once per month or once every few months, depending on the specific medication.
Gepants have a relatively short half-life, meaning they are cleared from the body more quickly. This allows for faster onset of action and makes them suitable for acute migraine treatment.
CGRP monoclonal antibodies have a longer half-life and remain in the body for an extended period, providing a sustained therapeutic effect that is suitable for migraine prevention.
Side effects and contraindications:
Gepants may have mild and transient side effects such as fatigue and nausea.
CGRP monoclonal antibodies are also generally well-tolerated with a low incidence of side effects. Some common side effects may include injection site reactions, constipation, and upper respiratory tract infections.