EAN 2026 | RESOLUTION: eptinezumab and patient education for chronic migraine and medication-overuse headache

I’m going to discuss the results of the RESOLUTION trial, which had a very interesting design, at least in my view. It enrolled patients who had chronic migraine, meaning headache on 15 or more days a month that are linked to migraine, and patients who had medication overuse headache. And the definition of medication overuse headache based on the International Classification of Headache Disorders criteria is based on the number of days per month that people take particular acute treatments. So for prescription drugs, for triptans, prescription combination of ingredient products, gepants, if you take a drug more than 10 days a month, that technically meets the definition of medication overuse headache. But for simple analgesics, for over-the-counter medications, for non-steroidal anti-inflammatories, you need to take the medication 15 or more days a month. Now, there’s controversy in how to manage chronic migraine with medication overuse headache. And to some degree, there’s a divide between the approach taken in Europe and taken in the United States. So in many centers in Europe, the standard treatment is before giving preventive medications, you withdraw the overused medication. And in order to do that, you give the patient education on the risk of medication overuse and instructions to discontinue their overused drug. When they get off the medication, only then would you start a preventive medication. The alternative approach, which is widely used in the United States and used in some centers in Europe, is to simultaneously prescribe a preventive medication and to educate patients on the risk of medication overuse without specifically providing detailed instructions on how to discontinue the medication or how to taper it.

So in the RESOLUTION study, everybody got a behavioral education intervention designed to instruct people on the risks of medication overuse and to encourage them to take less drug. In one arm of the study, people received eptinezumab, which is a CGRP-targeted monoclonal antibody. And in the other arm, people received a placebo intravenous IV infusion. So this study asks, if a patient gets a behavioral education intervention, do they do better also getting a highly effective preventive medication, in this case, eptinezumab versus the behavioral education intervention alone? And so this was a Phase IV study and showed in the 12-week data, the treatment with eptinezumab, there were reductions in migraine frequency, severity, disease burden, and improvements in quality of life in the eptinezumab arm versus in the placebo arm. And what’s now being presented is the 24-week data from the same study. And in this study, 608 patients were randomized, and a total of 593 were treated with eptinezumab in the open-label extension, and 584 of those patients completed the trial. We saw reductions in migraine frequency and also a reduction in the proportion of people who met diagnostic criteria for chronic migraine and for medication overuse headache over the course of the study. We also saw improvements across multiple patient-reported outcomes in post hoc analyses at 24 weeks and in the per protocol analyses at 12 weeks. The proportion of patients with treatment-emergent adverse events in the open-label study was similar in the group that got eptinezumab in the first 12 weeks and then eptinezumab in weeks 13 through 24 in comparison with the group that got placebo during the randomized phase and then eptinezumab. There were no new safety signals identified. So the conclusion we draw is that in participants with chronic migraine and medication overuse above and beyond the benefits of a behavioral education intervention, giving eptinezumab produces reductions in disease burden in the first 12 weeks, and those benefits are sustained for up to 24 weeks. In addition, in the group of people initially treated with placebo for the first 12 weeks, they catch up in terms of benefit when they are assigned to the eptinezumab arm for the open-label extension study. So in balance, then, this study favors not only offering a behavioral education intervention, but also preventive pharmacotherapy, in this case with eptinezumab, for the relatively refractory group of patients who have chronic migraine with medication overuse.

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