The State of Monoclonal Antibodies for Migraine

Hans-Christoph Diener, MD, PhD


July 15, 2022

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the University of Duisburg-Essen in Germany.

For this month's topic, I'd like to discuss monoclonal antibodies against calcitonin gene-related peptide (CGRP), or the CGRP receptor in the prophylaxis of migraine. CGRP plays an important role in the pathophysiology of migraine. It is released in large quantities during a migraine attack. And if you inject too much triptan, this lowers the concentration of CGRP in the bloodstream.

We now have four new monoclonal antibodies that were developed to bind CGRP or to block the CGRP receptor. Erenumab is given in doses of 70 or 150 mg subcutaneously every 4 weeks, fremanezumab at 225 mg every 4 weeks or 675 mg every 3 months, galcanezumab at 120 or 300 mg every 4 weeks, and eptinezumab intravenously at 100 or 300 mg.

Clear Efficacy

The efficacy of these monoclonal antibodies is established in terms of the 50% responder rate. The number of patients who have at least a 50% reduction in monthly migraine days is somewhere between 45% and 60%. And the mean reduction of migraine days per month is between 3 and 6 days.

These drugs are also effective in people who did not respond to prior monoclonal antibody therapy. We have data showing that efficacy in people who did not respond to at least three prior treatments — for example, with beta-blockers or topiramate. We also now have long-term results from registries for a duration of 1-3 years. These drugs do not lose efficacy, and they have an excellent adverse-event profile. Only about 3%-7% of patients will terminate the treatment due to adverse events.

We also have a head-to-head comparison between topiramate and erenumab. This showed that erenumab was clearly more effective and had fewer patients who dropped out due to adverse events. Overall, the adverse-event rate is somewhere between 3% and 6%. The most frequent adverse event is constipation, which is more frequently reported with erenumab than with the other monoclonal antibodies.

Other Considerations

Candidates for these new, but unfortunately expensive, drugs are patients who did not respond to the available therapies — for example, beta-blockers, fluorescein, amitriptyline, valproic acid, topiramate, or in the case of chronic migraine, onabotulinum toxin A. Other candidates are patients who could not tolerate these therapies or have contraindications.

The parameters for success are the 50% responder rate and the reduction in migraine days per month. And there's also the subjective verdict of the patient who says, "I am much better than I was before."

When it comes to the duration that these monoclonal antibodies should be used, we recommend 9-12 months. After that point, it makes sense to pause. After about 4-6 weeks, you can see whether the patient needs another course of monoclonal antibodies or has improved in such a way that treatment is no longer important.

Medication overuse headache is the most difficult-to-treat migraine condition. Thankfully, all of the monoclonal antibodies are effective in this condition. This is a big step forward because nowadays you would start first with topiramate or onabotulinum toxin A. If they are not effective, switch to a monoclonal antibody. And only if the monoclonal antibody is not effective, the patient has to undergo a medication pause or medication withdrawal.

Should we switch to another monoclonal antibody if the one being used is found to be ineffective? Yes. For example, if erenumab, which acts at the receptor, is not effective, it's possible to switch to fremanezumab, galcanezumab, and eptinezumab, and the other way around.

CGRP plays a very important role in the vascular system. It's the most potent vasodilator we have. And it also plays a role in the mucosa of the bronchial system and the gastrointestinal tract.

At present, we do not have enough quality safety data for particular patient groups. These include patients with serious vascular diseases like stroke, transient ischemic attack, subarachnoid hemorrhage, myocardial infarction, or unstable coronary heart disease and Raynaud disease. It also includes patients with inflammatory bowel disease, chronic obstructive pulmonary disease, and wound-healing problems. In addition, females who are pregnant or breastfeeding should not be treated, and these drugs are not approved for children and adolescents.

In conclusion, these drugs are a major step forward in the prophylaxis of migraine. They are highly specific. They have an excellent side-effect profile. But, unfortunately, at present they are very expensive, which limits their use in many health systems.

Dear colleagues, I am Christoph Diener from the University of Duisburg-Essen in Germany. Thank you very much for listening and watching.

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