New Migraine Drugs: What Independent Analyses Found

Hans-Christoph Diener, MD, PhD


April 11, 2023

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the Faculty of Medicine at the University Duisburg-Essen in Germany. This month, I would like to concentrate on the new treatments for acute migraine attacks and migraine prevention.

I think you are all aware that we have a number of new drugs, both for acute treatment and for migraine prevention. Unfortunately, almost all the publications dealing with these new substances were supported by industry; therefore, the International Headache Society decided to have a series of independent papers written by young headache specialists without conflicts of interest. These eight papers were published in Cephalalgia in March 2023; they are freely accessible, they are open access, and you can easily read them.

Acute Migraine Drugs

Let me start with the new drugs for the treatment of acute migraine attack. Standard therapy includes analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and triptans. We have two new classes of acute drugs. Lasmiditan is an agonist of the serotonin 1F receptor and works centrally. Then we have two gepants, rimegepant and ubrogepant, which act on the CGRP receptor.

The first study summarizes the results from seven trials with 12,800 patients. All active drugs were superior to placebo. The most effective new treatment was lasmiditan 200 mg. This drug, unfortunately, has a number of central side effects — in particular, concentration problems, tiredness, dizziness, and vertigo. The drug cannot be taken if you have to drive a car in the next 8 hours. Rimegepant and ubrogepant have very few side effects, but in indirect comparisons, they are less effective than the triptans.

The second publication deals with open-label, long-term, and observational studies with these new drugs. There are no surprises in terms of efficacy and adverse events. Ubrogepant, in two patients, showed increased liver enzymes, but it's not clear whether this is a causal relationship. The new drugs were effective long term in open-label studies, and there was no sign of tachyphylaxis.

The third publication deals with the value of the new migraine drugs in patients who do not respond to or have contraindications for triptans. Post hoc analyses from the published trials indicate that probably these new drugs are effective in triptan nonresponders, but we have no dedicated randomized trials in patients who are identified nonresponders to triptans. It seems that these new drugs, at least in open-label studies, are safe in people who have cardiovascular disease. It is possible to combine, for example, the gepants with monoclonal antibodies against calcitonin gene-related peptide (CGRP) given for migraine preventive therapy.

The fourth paper deals with the efficacy of monoclonal antibodies against CGRP or the CGRP receptor and gepants like rimegepant and atogepant for migraine prophylaxis. We have 19 studies with more than 14,500 patients for erenumab, eptinezumab, galcanezumab, and fremanezumab. Most of these studies were in episodic migraine and a few in chronic migraine. For all four monoclonal antibodies, there is clear efficacy and clear superiority over placebo. These drugs are very well tolerated. Rimegepant 75 mg every second day is also effective in migraine preventive therapy, but in indirect comparison, it's less effective than the monoclonal antibodies.

The fifth paper deals with the safety and tolerability of the monoclonal antibodies against CGRP and gepants. Here, we have also 19 trials with 14,500 patients. The study showed that these drugs are generally well tolerated. The highest adverse event rate was with 100 mg atogepant and 240 mg galcanezumab. Otherwise, there are no major differences between the monoclonal antibodies in terms of tolerability and safety. Erenumab has a slightly higher risk for constipation.

The sixth paper deals with the role of these new migraine preventive drugs in patients who did not respond to previous therapy, for example, with beta-blockers, flunarizine, topiramate, amitriptyline, and so on. This shows, in dedicated trials, that all these new drugs and new monoclonal antibodies are effective in people who did not respond to prior therapy.

Chronic Migraine

The seventh paper deals with the role of these new migraine preventive drugs in patients with chronic migraine, with and without medication overuse. We have here, again, studies that clearly show that the subgroup of patients with medication overuse and medication overuse headache responds to these new therapies, but these were all post hoc analyses. I think we should use these drugs, in particular, in patients with chronic migraine and medication overuse. At present, we have no data for rimegepant and atogepant.

The eighth paper deals with long-term and open-label studies for the monoclonal antibodies. There are 13 studies for the monoclonal antibodies and one for atogepant. These observational trials lasted up to 260 weeks. There were no new findings in terms of safety or adverse drug reactions. Over 75% of patients used these new migraine preventive treatments after 1 year, and there is no indication of loss of efficacy over time.

There was a separate paper, also published in Cephalalgia, presenting a meta-analysis of studies with the new monoclonal antibodies topiramate and onabotulinumtoxinA in patients with chronic migraine and medication overuse headache. The monoclonal antibodies and onabotulinumtoxinA were effective. The data for topiramate are relatively poor because these trials were done a long time ago.

Dear colleagues, it's worthwhile if you have time, for example, on the weekend, to access these nine papers, read them carefully, and hopefully learn about the new ways to treat migraine attacks and migraine preventive therapy. Unfortunately, the new treatments, at present, are very expensive, and therefore are limited to only a small number of patients.

I'm Christoph Diener from University of Duisburg-Essen. Thank you very much for listening and watching.

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