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New Era of Migraine Treatment and Prevention by Using New Anti-CGRP Drugs

Migraine is one of the most common neurological disorders that has been found in up to 20% of the total population worldwide. Women are 2-3 times more likely to develop migraine due to hormonal fluctuations such as before or during menstrual periods. Besides hormonal impacts, there are a number of migraine triggers including stress, sleep insufficiency, environmental stimuli e.g. strong odors, sunlight, temperature changes, pollution, and high tyramine food e.g. aged cheese and cured meats as well as drinks containing caffeine and alcohol.

Migraine can cause severe throbbing headache or pulsing sensation, usually on one side of the head. It is often accompanied by nausea, vomiting and extreme sensitivity to stimuli such as bright lights, loud noises and strong smells. Since migraine attacks can last for few days, it largely interferes with daily life and activities, resulting in impaired quality of life.

Recent medical researches have firmly indicated that Calcitonin Gene-Related Peptide (CGRP) – one of the neuropeptides, plays a important role in the induction of migraine attack. CGRP is a small protein that is highly prevalent in the sensory nerves that supply the head and the neck. CGRP primarily involves in blood vessel dilation (vasodilator) and pain transmission in the brain. During a migraine attack, the level of CGRP significantly increases. Therefore, CGRP inhibitors are used for the management of migraine, particularly to prevent migraine attacks and reduce its severity. A number of researches have demonstrated superior profile of CGRP inhibitors in terms of efficiency and high degree of safety.

Patients usually use pain killers during migraine attack. Medications used to treat acute migraine attack include nonsteroidal anti-inflammatory drugs (NSAIDs), triptans and ergotamine. However, some patients might face regular attacks almost daily and pain relievers sometimes are not effective, resulting in disturbances of daily activities, impaired work capability and poor quality of life. Thus, preventive treatment is considerably crucial in certain patients especially those who have frequent attacks with long-lasting or severe headaches, patients with lack of response to oral pain-reliever medications and who have contraindications or side effects caused by oral pain killlers.

Preventive medication is aimed at reducing the frequency and severity of migraine. Currrent options include anti-seizure drugs, antidepressants and blood pressure-lowering medications. However, these groups of medicines are not formulated to act directly against migraine, they only manifest to help reducing migraine frequency and severity with different mechanisms of action.

The discovery of CGRP, which is a neuropeptide that has strong association with migraine mechanism through the fifth cranial nerve or trigeminal nerve that is responsible for pain transmission in the head and neck, leads to the development of medication to inhibit this mechanism. Nowadays, there are 2 groups of CGRP inhibitors; CGRP monoclonal antibodies and CGRP receptor antagonists.

Clinical studies have suggested that CGRP monoclonal antibodies can decrease the frequency of migraine attacks and amount of pain killer medications used as well as improve quality of life. More importantly, CGRP monoclonal antibodies have demonstrated superior benefits in difficult to treat migraines such as chronic migraine, prior preventive treatment failure and medication overuse headache. CGRP monoclonal antibodies can be administered via subcutaneous injection and each dose lasts for up to a month. Additionally, these drugs demonstrate fewer side effects compared to other preventive medicines.  Mild and temporary adverse events, in comparison to placebo, might include pain or red skin at the injection site, mild upper respiratory tract infection and constipation. For long-term effects monitored in patients who had used these medication for 3-5 years, CGRP monoclonal antibodies have shown safety profiles in cardiovascular system without significant changes in blood pressure and heart rate. In addition, these drugs do not alter liver functions.

  

In conclusion, migraine largely interferes daily life and activities, affecting both physical and mental aspects as well as quality of life. Preventive treatment significantly helps reducing disease severity. CGRP monoclonal antibodies act specifically to prevent migraine attacks at its origin in the brain. These medications are highly suggested in patients who have chronic migraine without clinical responses to prior treatments. In addition, these medicines can be used safely in the long-term according to its current safety profiles.

Reference:

Dr. Kiratikorn Vongvaivanich

Neurologist, Bangkok International Hospital.