Target the mechanism involved
In fact, these drugs target for the first time a protein directly involved in the migraine mechanism. Named CGRP (for calcitonin gene-related peptide, in English), it facilitates the propagation of pain signals along the nerves. Its level in the blood increases sharply during migraine attacks.
Targeting CGRP has first proven effective in reducing the frequency of crises. Thus, since 2018, four monoclonal antibodies have been authorized in Canada: erenumab, fremanezumab, galcanezumab and eptinezumab, sold under the brand names Aimovig, Ajovy, Emgality and Vyepti. By clinging to CGRP, these antibodies prevent it from acting. They are injected subcutaneously or intravenously as a preventative measure, every month or every 3 months.
In the last two years, Health Canada has also approved another class of drugs targeting CGRP: gepants. Useful for short-circuiting seizures, but also for preventing them, they block CGRP receptor molecules. In other words, they prevent CGRP from triggering its painful cascade. They are administered orally (including ubrogepant, atogepant and rimegepant, sold under the brand names Ubrelvy, Qulipta and Nurtec). “Gepants are better tolerated than triptans and do not cause toxicity or rebound problems [céphalées causées par une surconsommation de médicaments] », specifies the Dre Leroux.
Heather Pim, director of the headache clinic at the University of Montreal Hospital Center, also considers that we are experiencing an “exciting” moment in the fight against migraine. New treatments have radically improved the quality of life of some of his patients. So one of them went from 25 migraine days a month to just one.
“It’s incredible!” exclaims the neurologist and current president of Migraine Québec. Obviously, there are super responders, who represent around 10% of cases, but most patients saw an improvement. »
A misunderstood evil
Unfortunately, not everyone benefits from this progress. First, because the anti-CGRPs themselves only seem effective in 30 to 60% of cases, depending on the studies. Then, and above all, because despite scientific advances, migraine remains poorly understood and poorly treated in the country. The disease is minimized by society, the workplace… and doctors. “We are witnessing a magnificent story of science and, there, we find ourselves with patients who do not have access to treatments”, deplores the Dre Elizabeth Leroux.
The disease is invisible, disproportionately affects women, and is not fatal; crises always end up calming down on their own. So many ingredients that harm the cause of patients, believes the specialist.
Moreover, a third of them feel stigmatized, which affects their quality of life and adds to the burden.
For the Dre Leroux, the key is the education of future doctors, particularly general practitioners, because few people suffering from migraines have access to neurology follow-up. “It takes more training, and a system to clarify care. There are guidelines, of course, but doctors still need to know them and apply them,” underlines the neurologist, who advocates the establishment in the country of a network of specialized clinics with multidisciplinary teams, as he exists in the United States and Europe.
In fact, even triptans are “largely underprescribed.” This was denounced by a meta-analysis published last fall, which analyzed 137 clinical trials carried out on a total of 90,000 people. The aim was to compare the effectiveness of 17 crisis treatments. Bottom line: triptans, particularly eletriptan, come out on top. They therefore remain options of choice, and the gepants enrich the arsenal. It is still necessary that all these options be offered to patients… “Sometimes, doctors do not feel equipped, due to potential side effects or risks,” recognizes Jonathan Hudon, family doctor at the Alan-Edwards Unit of pain management at the McGill University Health Center.
The fields of family medicine are vast, he recalls. And keeping up to date with the knowledge of each of them, in addition to knowing each new molecule on the market, remains a “constant challenge”.
In recent months, Guillaume began suffering from rebound migraines caused by triptans, a well-known side effect of this treatment. In consultation, his family doctor preferred to prescribe a classic but non-targeted preventive treatment, amitriptyline, an antidepressant, rather than a “seizure-busting” medication suggested by his pharmacist.
Antidepressants, antihypertensives and epilepsy medications are certainly effective in certain cases in preventing migraines, emphasizes Elizabeth Leroux. But they are not targeted. However, taking gepants to treat seizures can also help reduce their frequency. “It’s an interesting approach, but most family doctors are not aware of the existence of gepants,” she laments.
Insurance companies also complicate the task of doctors. Due to the high cost of anti-CGRP antibodies and preventative gepants, approximately $500 to $600 per month, insurance companies reimburse these medications only if patients have previously tried two to three oral treatments such as antidepressants without success. , which are ten times cheaper.
New proteins in the viewfinder
Although science has made great advances in recent decades, the migraine puzzle is not yet resolved. As proof, a Danish study carried out on mice and published in the journal Science made headlines this year: it offers a brand new mechanism for migraines with aura. Auras are transient neurological disorders, such as visual disturbances (flashes, bright spots, blurred vision, etc.), motor or language disorders, which precede the attack by a few minutes and affect 20 to 30% of migraine sufferers.
Scientists from the University of Copenhagen have found the previously unknown “communication channel” between the brain and the nerves that cause pain. They showed that proteins secreted during the aura travel directly in the cerebrospinal fluid (CSF), in which the brain bathes, to a nerve center called the trigeminal ganglion. This ganglion plays a crucial role in migraine: it is from there that the sensory nerves originate which radiate towards the face… and which cause the pain.
This discovery could lead to new treatments. “What’s exciting is that we have a whole new set of molecules to study [dans le LCR]which could be useful in the design of treatments for people who have little or no response to CGRP blockers,” underlines Martin Kaag Rasmussen, lead author of the study.
The researcher is hopeful that the discovery of treatments will accelerate. “Neurology in general hasn’t evolved that much in the last 50 to 60 years, but I feel like it’s starting to change. Treatments developed with anti-CGRP antibodies have shown a way forward,” believes the postdoctoral researcher at the Center for Translational Neuromedicine at the University of Copenhagen.
He sees in the more or less near future the development of a completely personalized treatment according to the protein production of each patient. We could then “adapt the treatment to the person, with a catalog of clinically approved antibodies [et bloquant différentes protéines impliquées dans la migraine] », he hopes.
Elizabeth Leroux also believes that there will never be a universal treatment and that approaches will have to be personalized. As for curing migraine for good, the hope is slim, because migraine is too multifactorial. On the other hand, the neurologist remains optimistic “We will control the pain and other symptoms in an excellent way,” she rejoices.
* Guillaume preferred to remain anonymous so as not to harm his relationship with his doctor.
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