Unearthing the Year’s Clinical Highlights in Migraine

Medication overuse headache is a persistent problem for headache sufferers around the world and is a frequent complaint to providers.

As one of those providers, Messoud Ashina, MD, PhD, DMSc, a professor of neurology at the University of Copenhagen, presented an overview of his clinical takeaways for 2020 with a review of findings from 4 areas at the Migraine Trust International Symposium. In addition to medication overuse headaches, he focused on migraine prevention, migraine pathophysiology, and cluster headache pathophysiology.

Medication Overuse Headaches

These types of headaches occur in conjunction with migraines, and understanding how to stop them is one of the questions facing clinicians, Ashina said. One of the problems, however, is that there is a paucity of randomized controlled trials examining strategies.

However, earlier this year a paper published in JAMA Neurology looked at the results of a comparison of 3 treatment strategies of 120 patients divided into 3 groups. The 3 groups were withdrawal plus preventive medication, preventives only, or withdrawal plus postponed preventives.

Headache days per month were reduced by 12.3 (95% CI, 9.3-15.3) in the withdrawal-plus-preventive group, by 9.9 (95% CI, 7.2-12.6) in the preventive group, and by 8.5 (95% CI, 5.6-11.5) in the withdrawal group (P = .20).

Withdrawal and preventive medication was the most effective, he said. “Based on these data we can offer or suggest this type of regimen, withdrawal, and preventative for the treatment of medication overuse headache,” he said.

Migraine Prevention

Turning to migraine prevention, he noted that the major results from phase 3 studies published this year focused on eptinezumab, which is different than other biologics because it is given by infusion. In PROMISE-1 (episodic migraine) and PROMISE-2 (chronic migraine), 100 or 300 mg significantly reduced migraine frequency, was well tolerated, and had an acceptable safety profile for either condition, he said.

Assoud also discussed oral calcitonin gene-related peptide (CGRP) receptor agonists belonging to a class of drugs known as “gepants” used for the acute treatment of migraine. Two are available in the United States: ubrogepant and rimegepant.

One study published earlier this year aimed to answer the question as to whether these small molecule drugs can also be used for migraine prevention. The phase 2/3b study looked specifically at atogepant, which is still under development, for the prevention of episodic migraine in adults. The multicenter, double-blind, placebo-controlled trial randomly assigned adults 2:1:2:2:1:1 to receive placebo or atogepant 10 mg once daily, 30 mg once daily, 60 mg once daily, 30 mg twice daily, or 60 mg twice daily, in matching capsules.

All doses were associated with a significant decrease in monthly migraine days over 12 weeks compared with placebo, and it was safe and well tolerated over 12 weeks; of note, Assoud said, was that treatment-emergent adverse events were 5% for atogepant and 3% for placebo, and all were unrelated to treatment.

Migraine Pathophysiology

“As a scientist, I consider that biomarker of migraine is one important puzzles that we have in migraine,” Assoud said. But finding these biomarkers has proven to be a difficult task.

Earlier this year, a unique, complex imaging study attempted to discern what occurs in the brain during the premonitory phase of migraine. Conducted in Germany, it involved 9 patients with episodic migraines (2 male, 7 female) who underwent trigemino‐nociceptive, olfactory, and visual stimulation for 30 straight days. Moreover, each stimulus was used on the patient 15 times per day.

Functional MRI scans were taken before, during, and after the trial induced migraine pain in these patients, as well as interictal scans. Seven patients were included in the final analysis.

Hypothalamic activation, which was present up to 2 days before the onset of headache, but not in the pain phase and not in the postictal phase, is a potential marker for the premonitory phase of migraine, according to the results of the novel study.

Assoud called it “a very difficult study” with interesting preliminary results before moving on to discuss several other studies published this year.

Cluster Headache Pathophysiology

Lastly, he discussed cluster headache attacks, known causes of which include nitric oxide and CGRP. One study, on which he was a coauthor, examined whether vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) provoked cluster headache attacks as well. The hypothesis in the study was that PACAP38 would provoke the cluster headache, but that VIP would not.

The double-blind crossover study included 14 patients with episodic cluster headache in active phase, 15 patients with episodic cluster headache in remission phase, and 15 patients with chronic cluster headache. They were randomly allocated to receive intravenous infusion of PACAP38 (10 pmol/kg/min) or VIP (8 pmol/kg/min) over 20 min on 2 study days separated by at least 7 days.

However, much to the researchers’ surprise, both induced attacks for episodic and chronic headaches in the active phase.

These findings support the rationale for antibody testing for PACAP38, he said.