Predicting response to migraine treatment

Updated on 3/5/23

Even the best migraine medications work for only about half of the people who try them. In the next decade or so, advances in pharmacogenomics, neuroscience, and artificial intelligence will allow us to predict who is going to respond to which drug. This will eliminate the trial-and-error approach we have to use now.

German researchers led by Dr. Uwe Reuter just published a study that attempts to predict who is going to respond to injections of CGRP monoclonal antibodies (mAbs) that are used for the prevention of migraines. These drugs include erenumab (Aimovig), galcanezumab (Emgality), and fremanezumab (Ajovy). The fourth drug in this family that is given intravenously, eptinezumab (Vyepti) was not available in Germany at the time of the study.

They compared super-responders (patients with 75% or greater reduction of monthly headache days) with non-responders (patients with 25% or lower reduction of monthly headache days after trying all three mAbs). Of 260 patients with chronic and episodic migraine they evaluated, 11% were super-responders, and 10% were non-responders.

Non-responders were more likely to have chronic migraines. Super-responders were significantly more likely to report good improvement of their acute migraine headache with a triptan. Non-responders were more likely to have depression and overuse acute medications.

It was interesting that only 10% of patients were non-responders. The authors explained this by the fact that they had to fail all three mAbs to be considered non-responders. An earlier German study showed that one-third of patients who did not respond to erenumab did respond to galcanezumab or fremanezumab.

The low number of super-responders to mAbs could be due to the fact that the German government pays for this treatment only if there is treatment failure or intolerable adverse events with all first-line preventives (beta-blockers, topiramate, flunarizine, amitriptyline and for chronic migraine, also OnabotulinumtoxinA, or contraindications to those. In the large clinical trials that led to the approval of mAbs, there was no such requirement and the results were much better.

Another study recently published by Sait Ashina and others in Rami Burstein’s group at Harvard showed that people who have increased skin sensitivity between migraine attacks (allodynia) are more likely to respond to galcanezumab.

These studies describe only trends and at this time have limited practical application. Patients who are depressed, overuse acute drugs, suffer from chronic migraines, or have interictal allodynia may still respond to mAbs. This information, however, may lead to more accurate prediction models when it is combined with genetic, imaging and other new data.