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Commentary: Predicting Migraine Treatment Outcomes, July 2024

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Heidi Moawad, MD

Evidence is emerging to help identify predictors of migraine treatment outcomes. Additionally, research is beginning to pinpoint lifestyle factors that have a measurable effect on migraine frequency, severity, and duration. Guiding patients to select beneficial lifestyle interventions can influence their migraine-associated quality of life and reduce the need for medication and other interventions. Knowing which patients might or might not benefit from specific medication classes can help in selecting the right therapies, potentially shortening the "trial and error" process that many patients must actively participate in as they assess which migraine treatments are most effective and tolerable.

Medications classified as anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb), a relatively new category of migraine therapy, have shown strong evidence of efficacy for migraine treatment and prevention. However, as these medications — which include Aimovig (erenumab), Emgality (galcanezumab), Ajovy (fremanezumab), and Vyepti (eptinezumab) — are new, their long-term outcomes are not known; in addition, they are expensive and they do not work for everyone. Patients who are doing relatively well on other medications might ask about switching to one of the anti-CGRP mAb so that they can experience the better outcomes and low side-effect profile that they've been hearing about. New research is showing some prognostic indicators that can help identify which patients might experience a better response to anti-CGRP mAb.

A prospective real-world study published in the May 2024 issue of Journal of Neurology, Neurosurgery, and Psychiatry included 5818 patients who had been treated with an anti-CGRP mAb for high-frequency episodic or chronic migraine. The researchers assessed responses after 6 months of use, defining a good response as ≥50% reduction in monthly headache days and excellent response as ≥75% reduction in monthly headache days. They found that several pretreatment baseline factors were predictors of a good or excellent 6-month response: older age, the presence of unilateral pain, the absence of depression, fewer monthly migraine days, and lower Migraine Disability Assessment (MIDAS) score. Notably, men and women experienced comparable outcomes. While it's not completely clear why these factors were associated with better responses to anti-CGRP mAb, the results could help in selecting patients who might or might not benefit from this new medication class.

Results of a prospective study published in the May 2024 in The Journal of Headache and Pain demonstrated that patients treated with eptinezumab for 3 months experienced a reduction of monthly headaches, migraines, and the use of acute medication. The patients who had previously had an inadequate response to or were unable to tolerate other anti-CGRP mAb (erenumab, galcanezumab, fremanezumab) were less likely to experience improvement with eptinezumab than patients who had not had previous unsuccessful attempts with anti-CGRP mAb. This suggests that it might not be beneficial for patents to try multiple medications in this category if they have had an inadequate response or intolerability to others in the same drug class.

Lifestyle factors can play a role in migraine outcomes and may reduce the need for medication. A study published in The Journal of Headache and Pain in May 2024 examined the relationship between migraine and the American Heart Association (AHA) Guidelines for Cardiovascular Health recommended lifestyle factors. The study included 332,895 participants, with a median follow-up of 13.58 years. Researchers found that maintaining targeted or recommended body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk.

Diet, another lifestyle factor, can also have an effect on migraine. Avoiding dietary triggers is a well-known adjustment that many patients are advised to make. Overall diet quality can play a role in migraine outcomes as well. According to a study published in the May 2024 issue of Nutritional Neuroscience, participants who followed a diet that qualified as having a high Carbohydrate Quality Index (CQI) had lower migraine severity and duration than participants whose diets did not qualify as high CQI. The study included 266 women (age 18-45 years), using a 147-item food frequency questionnaire to assess CQI. The CQI, a relatively new index for measuring carbohydrate quality, includes four components: glycemic index, dietary fiber intake, ratio of whole grain to total grain, ratio of solid carbohydrates to total (solid + liquid) carbohydrates.1 A low glycemic index and higher scores for the other three factors translates to a high CQI.

While the results of the AHA/migraine study and the CQI/migraine study are interesting, the physiologic reasons for the outcomes and validation of the results need further investigation. It's not clear whether the decrease in migraines that's associated with optimal carbohydrate intake is associated with outcomes such as low BMI or better sleep, or whether carbohydrate metabolism could be an independent factor.

Predictive factors can be beneficial in making migraine treatment decisions. While trial and error will always remain part of optimal migraine therapy, customizing treatment on the basis of an individual patient's characteristics can help in reaching an effective treatment and better quality of life sooner.

Additional References

1. Sawicki CM, Lichtenstein AH, Rogers GT, et al. Comparison of indices of carbohydrate quality and food sources of dietary fiber on longitudinal changes in waist circumference in the Framingham Offspring Cohort. Nutrients. 2021;13:997. Source

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