New Era in Migraine Therapy

Primary Headaches

Headaches are among the most common reasons for visiting a general practitioner or neurologist. Generally, they can be divided into primary and secondary. In primary headaches, there is typically no clear structural cause, such as a tumor or other organic lesion. Secondary headaches are symptomatic of more severe pathology and often require immediate attention. Hence, it's always necessary first to exclude possible causes of secondary headaches. According to the latest classification from 2018, primary headaches include, in addition to migraines, tension-type headaches and trigeminal autonomic cephalalgias.

Migraine and Its Treatment

Migraine therapy is conducted in two avenues – treating the acute phase and preventive treatment. The medications used in acute phase therapy depend on the severity of the symptoms. Mild cases can be managed with readily available analgesics like acetylsalicylic acid (ASA) or paracetamol. Moderate to severe migraine attacks require treatment with triptans. These are a group of substances that penetrate the blood-brain barrier and bind to specific 5-HT_1B/_1D receptors located in the brain arteries. Binding to these receptors induces vasoconstriction of intracranial vessels.

Repeated or prolonged migraine attacks significantly reduce the patient's quality of life, to some extent exhaust the body, and adversely affect the individual's psychological condition. According to recently published studies, having at least four episodes of acute migraine attacks per month reduces the quality of life by 20%. Data from Czech patients are also interesting. They usually miss work approximately every 5th to 7th day due to an acute migraine attack.

For such patients, the only option is a well-set and effective preventive therapy. This requires long-term use of medications, usually over several months. Preventive treatment for migraines includes beta-blockers, calcium channel blockers, antiepileptics, antidepressants, serotonin antagonists, or nonsteroidal anti-inflammatory drugs.

A New Era of Therapy – Monoclonal Antibodies

Although it might not seem so to many, migraine is a serious neurological disease. It is the 3rd most common disease in the world. However, it is often underdiagnosed or even incorrectly diagnosed and treated ineffectively. Therefore, biological treatment for migraine, which appears very promising for those who do not benefit from commonly available pharmacotherapy, is a new hope for patients.

The first biological drug approved by the US Food and Drug Administration (FDA) for migraine prevention was erenumab (Aimovig) in May 2018. It is a monoclonal antibody (mAb) against receptors for calcitonin gene-related peptide (CGRPR). Abnormal CGRPR signaling plays a key role in the pathogenesis of migraines. The endogenous ligand CGRP is released from trigeminal perivascular nerve endings and upon binding to the receptor, massive vasodilation and the release of neurotransmitters occur to modulate nociception and neurogenic inflammation.

The advantage of monoclonal antibodies is their high specificity, low toxicity, and relatively long half-life. Importantly, they are neither metabolized in the liver nor eliminated by the kidneys. No pharmacological interactions are known either. Study results clearly indicate the positive effect of biological treatment. In about half of the patients, the frequency of attacks per month decreased by about 50%, with some even reporting a 75% reduction or complete absence of migraine attacks.

The onset of effect is also individual. Patients typically notice a change within 2 months, though occasionally within a few days. Generally, however, if the effect is not achieved within 3 months of starting the treatment, it is likely ineffective for that patient.

A relative disadvantage is the cost of the treatment, which is still only available in specialized centers. The recent novelty, however, is the approval of reimbursement from public health insurance as of February 2020, with a copayment in the range of several hundred crowns.

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Sources: Garces F., Mohr C., Zhang L. et al. Molecular insight into recognition of the CGRPR complex by migraine prevention therapy Aimovig (erenumab). Cell Rep 2020; 30(6): 1714−1723.e6, doi: 10.1016/j.celrep.2020.01.029.