Headaches and migraines not only impair the lives of those affected, but also cause economic damage. Newly developed antibodies specifically target the molecular development process of migraines and can thus preventively reduce the likelihood of migraine attacks.

By Hartmut Göbel

 

Every day in Germany alone, approximately 900,000 people suffer from migraine attacks, and 100,000 are unable to work and bedridden due to migraine attacks. This makes migraine the third most common human illness worldwide, after tooth decay and headaches, and it is the leading cause of disability among people under 50. On average, three million Germans take a headache tablet over the counter every day. In addition, almost 60,000 single doses of triptans, specific acute migraine medications, are used daily nationwide to treat migraine attacks. The disease also has a significant economic impact: headaches are among the most frequent reasons for short-term sick leave. The number of days lost to migraine-related absences in Germany alone is equivalent to the annual working hours of 185,000 full-time employees – with estimated costs of 3.5 billion euros. Added to this is the loss of productivity due to unpaid work in the household, childcare, or caring for relatives. The risk of cardiovascular disease, heart attack, and stroke is 1.5 to 2 times higher than in healthy individuals, while the risk of developing depression, suffering from an anxiety disorder, or committing suicide is three to seven times higher for migraine patients. The total annual cost of headaches among 18- to 65-year-olds in Europe amounts to over 170 billion euros. And yet, across Europe, less than 20 percent of those affected receive medical care, and less than 10 percent receive guideline-based prevention or acute treatment.

 

Gene variants increase the risk of disease

New research has revealed that migraine patients exhibit numerous genetic variations. Currently, 38 gene loci with 44 gene variants are known to increase the risk of developing migraines. These gene variants are responsible for nerve impulse transmission, sensitivity, and processing. Furthermore, they regulate the energy supply to nerve cells and arterial walls. These membranes surrounding the blood vessels are the largest endocrine organ, producing numerous messenger substances that control blood flow and regulate inflammatory responses. Many substances relevant to important regulatory processes in the body are also activated here. A disruption in energy supply, for example, due to oxidative stress, can throw this regulation off balance and trigger malfunctions. Therefore, both genetic predisposition and environmental, behavioral, and social factors play a significant role in the development of migraine attacks. If nerve function malfunctions, inflammatory substances can be released at the arteries of the meninges, leading to increased sensitivity of the meninges. Every heartbeat causes a throbbing, pounding pain; every movement of the head hurts. Therefore, migraine sufferers try to lie down whenever possible, severely restrict physical activity, and avoid jarring movements.

 

Antibodies can reduce migraine attacks

In recent years, researchers have succeeded in developing specific antibodies against messenger substances that trigger inflammation during a migraine attack. The focus here is on calcitonin gene-related peptide, or CGRP for short, which is one of the most potent vasodilators and plays a key role in the development of migraines. When patients receive so-called monoclonal antibodies, the effects of these inflammatory substances can be blocked for several weeks, thus reducing the likelihood of migraine attacks. The antibodies erenumab, galcanezumab, fremanezumab, and eptinezumab have now been developed, which act directly against CGRP or block the CGRP receptor. These four drugs have been tested in numerous large-scale, international studies, and their efficacy has been demonstrated. Study data are available for episodic migraine with up to 14 migraine days per month and for the chronic form with more than 15 migraine days per month. The study investigated, among other things, whether the new antibodies are also effective in patients who did not respond to currently approved preventative medications. However, comparative studies with existing preventative medications are not yet available. Annual therapy costs are expected to be between €6,000 and €10,000, but it is currently unclear which types of migraine and which patients will be eligible for reimbursement by health insurance companies. To ensure cost-effectiveness, the new immunotherapy will likely only be considered when currently available migraine medications are ineffective, not tolerated, or contraindicated in a patient. Erenumab, the first of the four antibodies, was approved in Germany in July and will be available in pharmacies starting in November of this year.

 

Immunotherapy specifically for migraine prophylaxis

The antibody is injected every four weeks using an autoinjector, similar to an insulin pen. Because this immunotherapy is a passive immunization, in which the antibodies are not produced by the body itself but manufactured in the laboratory, the injection must be repeated regularly. Unlike all other currently available preventative medications, this new therapy was developed specifically for migraine prophylaxis. A slow dose escalation due to intolerances and side effects is not necessary. The effect occurs within a few days, whereas with previously available preventative medications, the effect is often only achieved after weeks or even months. Side effects such as weight gain, mood swings, fatigue, reduced energy, or drowsiness do not occur. In contrast to previous medications, which are often discontinued after a short time due to these side effects, patients treated with this therapy remain on it long-term due to its good tolerability and efficacy. However, the data available so far show that the new immunotherapy does not stop migraines, but merely reduces the risk of attacks: On average, headaches are reduced by approximately one to three days per month. This makes the effectiveness of the new vaccine similar to that of existing preventative medications. However, the advantages outweigh the disadvantages: The effect is rapid, the medication is well tolerated, and even patients who have not responded to other treatments respond to the therapy. Therefore, many more patients can certainly be helped in the future to reduce the debilitating migraine attacks and thus return to a relatively normal life.

 

Professor Dr. med. Dipl.-Psych. Hartmut Göbel , a specialist in neurology, is the founder and director of the pain clinic and the migraine and headache center in Kiel. He is also the initiator and head of the nationwide headache treatment network.

Article in the Frankfurter Allgemeine Zeitung from October 26, 2018