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The Impact of CGRP Antagonists on Chronic Migraine

David Kudrow, MD: How has the introduction of CGRP [calcitonin gene-related peptide] antagonists affected the treatment of chronic migraine? In my experience, vastly. I was a principal investigator in many of the phase 2 and phase 3 clinical trials that evaluated both monoclonal antibodies against CGRP and the small molecule antagonist studies. I had a pretty early view of what these medications were doing in patients with both episodic and chronic migraine. I wouldn’t limit the discussion to chronic migraine.

My practice is a headache specialty practice. Many of my patients have been on preventive medications in the past that they couldn’t tolerate or weren’t very effective for them. We had many patients who initially responded well to the anti-CGRP monoclonal antibodies for migraine prevention. Not only did they respond by having a reduced frequency of monthly migraines, but they also reported that they had an improved quality of life. They were no longer feeling anxious about having migraine, when they were going to have another migraine, how they had to plan their day, or whether they were going to have enough acute medication to last them a month for their migraines. From that perspective, I was very impressed early on with how initially the monoclonal antibodies and all 4 of them were very effective in helping reduce pain and suffering due to migraine.

What has been the effect of the introduction of CGRP antagonists on patients’ quality of life? A lot of the time, the top-line results reported for these clinical trials is reduction in frequency of migraine, which is reduction in the mean monthly migraine days compared with placebo, or the proportion of patients who achieve a 50% or better reduction in monthly migraine days. Traditionally, the metrics of success are reduction of migraine days and, conversely, an increase in migraine-free days. But from a more patient-centric perspective, what do the patients really care about? They care about less disability, not having to miss days at work, and not having to miss days with their family or social events or occasions. They care about quality of life and not having to worry about having migraine or having enough medication.

In many of the phase 2 and phase 3 clinical trials, not only did we see that patients were having a reduction in the frequency in their migraine days, but they also had an improved quality of life. We use the Migraine-Specific Quality of Life Questionnaire and the Migraine Disability Assessment scale to look at those things. In each case of these new therapeutics, patients are also recording improvements in their quality of life. On a daily basis, patients say to me, “I’m doing so much better than I was before. I feel much better.” I attribute that to the introduction of an effective therapy with a good adverse effect profile for them.

Another question is, what about reversion from chronic to episodic migraine? There was a paper published in 2019 looking specifically at that question. We looked at patients who had chronic migraine and, over the course of a 12-week double-blind, placebo-controlled study, looked at what proportion of those patients reverted to episodic migraine, meaning going from at least 15 headache days per month to below 15 headache days per month. The post hoc analysis showed that better than 50% of patients went from chronic migraine to episodic migraine. What was really interesting about that analysis was that patients who we’ve always regarded as the most intractable patients—patients who had prior preventive treatment failures and patients who were also experiencing medication overuse—showed a greater rate of reversion from chronic to episodic in comparison with patients who were on placebo.

Transcript edited for clarity.

Neurologylive

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