Headache Experts on What's Hot in Migraine

John Watson


September 04, 2018

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In late June, the American Headache Society (AHS) held its 60th Annual Scientific Meeting in San Francisco. Medscape spoke with experts in the field of migraine to hear about the presentations and abstracts they considered most intriguing from this year's meeting.

An Illuminating Lecture on Migraine and Comorbidities

Dr Harold G. Wolff was a pioneering neurology researcher with an interest in the role that physical and environmental factors play in the development of disease and illness. This year's recipient of the award given in Wolff's name was Richard B. Lipton, MD, FAHS, director of the Montefiore Headache Center and vice chair of neurology at the Albert Einstein College of Medicine in Bronx, New York. This marked the fifth time Lipton was given this award.

In an accompanying lecture, Lipton discussed his and his colleagues' attempts to bring greater clarity to the heterogeneous disease that is migraine. Their results, the latest from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study, were recently published in Headache.[1] CaMEO identified eight distinct subgroups of migraine on the basis of underlying patterns of comorbid health problems.

According to the experts we spoke with, it was a clear highlight of this year's meeting.

"I found the talk fascinating," said Jessica Ailani, MD, director of the MedStar Georgetown Headache Center and associate professor in the department of neurology at Georgetown University in Washington, DC. "I have wondered for some time in clinic if certain comorbid conditions predict more refractory disease and what impact they have on migraine."

CaMEO reported an association between a greater number of comorbidities and higher rates of severe disability, medication overuse, chronic migraine, and aura.

Lipton's findings also offered valuable insights into the potentially false factors that patients believe contribute to migraine, according to Deborah Friedman, MD, MPH, FAHS, chief of the division of headache medicine at UT Southwestern Medical Center in Dallas, Texas.

"My takeaway from his talk was that many of the so-called triggers are not triggers at all but contribute to trigger-associated anxiety and avoidance behaviors," Friedman said.

Lipton presented the example of a patient who believed that weather changes, which he saw coming up on his smart watch, triggered his migraines. The patient would proactively bunker down and begin medication when weather fronts approached.

"Dr Lipton's treatment was to take the watch away and—guess what—weather fronts were not triggering his migraines after all. It was the anticipatory anxiety about an incoming front that triggered them," Friedman explained. "The same thing likely happens with other triggers and can lead to extreme and unnecessary lifestyle modifications and social isolation."

Migraine's Causes and Costs

Two abstracts presented at this year's AHS meeting shed further light on the contributors to and costs of migraine.

"There was a small retrospective review[2] on the impact of menopause and migraine that had some surprising results," Ailani said. Researchers found that among women 40-60 years of age with migraine history, 60% experienced pattern changes, worsening of headaches, or new-onset migraine, which mostly occurred during the peri- or postmenopausal stage. As Ailani notes, this is "more common than in past reports."

Additional data from the CaMEO study shed light on the considerable toll that migraine takes on personal lives. Compared with those with episodic migraine, patients with chronic migraine were significantly more likely to report relationship problems (15% vs 37%; P < .001). This manifested in difficulties moving in with significant others, getting married, and other major life choices.[3]

Laine Green, MD, assistant professor in the division of neurology at Dalhousie University in Halifax, Nova Scotia, pointed to one particularly notable finding from the study: "Three percent to 10% of people made different choices on having children because of headache!"

Continued Promise for Novel Monoclonal Antibodies

Green highlighted the large number of abstracts in support of humanized monoclonal antibodies that bind to calcitonin gene-related peptide. Erenumab was studied in multiple studies, with Green singling out a 3-year follow-up study[4]—the only long-term analysis to date with this treatment—as particularly noteworthy. Data from 235 available patients participating in an open-label extension study showed that "side effects appear to be the same from the original trial."

The several abstracts presented from the phase 3 PROMISE-2 Trial in chronic migraine collectively told an encouraging story of eptinezumab's safety and efficacy, according to Green. Compared with those receiving placebo, approximately 60% of patients in the two eptinezumab treatment arms (100 and 300 mg) achieved a ≥ 75% reduction in monthly migraine days (MMD).[5] Significantly more patients receiving eptinezumab at 100 and 300 mg had 100% reductions in MMD each month when compared with placebo (10.8% and 15.1% vs 5.1%, respectively; P < .0001). Half of the patients who received eptinezumab achieved meaningful reductions in migraine activity as early as day 1.[6] Eptinezumab's safety profile was consistent with that observed in earlier trials.[7]

Post-hoc analyses of phase 3 studies of galcanezumab indicated that it had rapid onset of effect at week 1 in patients with episodic migraine, compared with placebo.[8] A separate post-hoc analysis of phase 3 trials in both episodic and chronic migraine revealed that galcanezumab's treatment effect may be greater in those with a history of not benefiting from preventive treatments and who used a triptan at baseline.[9] Additional data from the EVOLVE-1 and EVOLVE-2 trials in episodic migraine showed that patients receiving galcanezumab had significant and clinically meaningful improvements in daily functioning and decreased disability when compared with those assigned to placebo.[10]

Fremanezumab was also the subject of several studies. Phase 3 results in patients with chronic migraine showed that it led to reductions in overuse of acute medications and a corresponding decrease in days using acute medications.[11] Treatment with fremanezumab also demonstrated the potential for reversion from chronic to episodic migraine.[12]

Collectively, these results suggest the viability of monoclonal antibodies that target the calcitonin gene-related peptide. All eyes will be on next year's AHS meeting to see if this strong performance continues with additional study.


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