Challenge Case Report: Increasing Frequency of Migraine

Discussion

Migraine may be distinguished from other headache disorders because attacks are moderate to severe and present unilaterally with pulsating pain that worsens with exertion or interferes with the ability to be physically active. To be considered migraine, attacks must also present with 1 of the following symptoms: photophobia or phonophobia and nausea or vomiting. Some attacks also present with auras—sensory disturbances—preceding or occurring with the onset of the headache. Visual auras, as noted in our case, are the most common.¹

The differential diagnosis also includes cluster headaches and tension headaches. Cluster headaches are characterized by attacks of severe, unilateral pain in the orbital, supraorbital, and temporal regions. They last between 15 to 180 minutes and occur in a cyclic pattern, often worse at night. Tension headaches present with bilateral pain usually described as pressure or tightening. The location of the pain is in the forehead, temples, posterior head, and neck. These headaches can last between 30 minutes and 7 days.

The monoclonoal antibody CGRP inhibitors are prophylactic medications that are FDA approved for individuals with episodic or chronic migraine occurring 8 or more days/ per month or, less frequently, if attacks are disabling. There are 3 FDA-approved CGRP inhibitors, erenumab, fremanezumab, and galcanezumab.

The levels of CGRP have been found to be elevated during an acute migraine attack and CGRP infusion causes an attack in people with migraines.² The CGRP inhibitors work by blocking CRPG, which is released from the trigeminal ganglia. Galcanezumab-gnlm and fremanezumab-vfrm block CGRP by binding to the CGRP molecules. Erenumab-aooe blocks the CGRP receptor site on blood vessels.

Given that the half-life of the 3 FDA-approved mooclonal antibody CGRP-inhibitors are between 27 and 31 days, the recommended dosage schedule is a self-administered subcutaneous monthly injection. This schedule has been found to optimize the efficacy of CGRP inhibitors by reducing the number of days per month with a migraine and reducing the reliance of abortive medication.^3-5

The primary endpoint for the erenumab phase 3b double-blind placebo-controlled trial was the proportion of participants with at least a 50% reduction in migraine days, based on their personal baseline, during the third month of treatment. The study found that significantly more participants treated with erenumab than those treated with placebo had a 50% reduction in migraine days.

The primary endpoint for this study was the mean change from baseline in the number of monthly migraines over the 3-month treatment period. The study evaluated 1,113 participants in a randomized double-blind trial and showed a significant improvement in the number of monthly migraine days (P<.001). At least a 50% reduction in migraine days per month occurred in 62% of participants, and 39% had at least a 75% reduction. Additionally, there was a significant reduction in days when acute headache medication was taken (P<.001). The baseline effect of migraine on daily activities began at 51.4, with 100 being the worst impact. After 3 months, the mean change from baseline was 32.4.⁵

Side effects noted for all 3 monoclonal antibody CGRP-inhibitors include injection-site reactions (eg, pain, redness, swelling, itching, blistering, rash, or hives around the injection site).⁵ Erenumab has a unique side effect of constipation (answer C). In 1% to 3% of participants, hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, urticaria, and rash have been reported.

Conclusion

The CGRP inhibitors are a valuable treatment option for people with migraines, specifically those with migraine who have previously failed 2 to 4 other treatments.⁶ In a phase 3b study, erenumab was shown to decrease migraine frequency by 50% from baseline, a notable improvement in this population with refractory migraine.⁷ In the third month of the trial, 30% of participants had a 50% reduction in migraine days from their individual baseline vs 17% with placebo.⁶ Additionally, CGRP inhibitors have been shown to be well tolerated with minimal adverse effects. CGRP inhibitors are the first migraine-specific prophylactic medication, as they target the mechanisms underlying migraine pain. Additional therapeutic medications targeting CGRP are in development for prophylaxis and acute treatment of debilitating migraine headaches. The first CGRP-targeting acute migraine treatment, ubrogepant, was approved in December 2019. These novel medications offer hope and the potential for relief for the 4 million people worldwide who are affected by migraine headaches.