Fewer migraine days with dual therapy

Combination therapy with an anti-CGRP* monoclonal antibody (mAB) and onabotulinumtoxinA may be more effective than either therapy in patients with chronic migraine, according to a new study.

Chronic migraine is characterized by 15 or more headache days per month with at least eight of these fulfilling the criteria for migraine. [Front Pain Res (Lausanne) 2021;2:705276]

“Not only does this debilitating disorder affect general health and functioning. People with chronic migraine may be the toughest to treat,” said study investigator Dr MaryAnn Mays from the Headache and Facial Pain Clinic, Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, US. “They have the greatest disability, and very often, insurance companies would prefer monotherapy.”

A multifaceted approach using different agents targeting different pathologies may provide greater benefit in reducing the frequency and severity of migraine, she added.

“OnabotulinumtoxinA selectively inhibits unmyelinated C-fibers but not Aδ-meningeal nociceptors. Anti-CGRP mAb therapies, on the other hand, have been shown to prevent the activation of Aδ fibers but not C-fibers,” Mays said.

Dual vs monotherapy

The researchers assessed the medical records of 194 patients who had been treated with anti-CGRP mAbs and onabotulinumtoxinA. Over 86 percent of the cohort were women between 36 and 65 years of age. The average monthly migraine days were 28. [AHS 2023, abstract P-183]

Monthly migraine days were assessed at 3 months after monotherapy with an anti-CGRP mAb or onabotulinumtoxinA injections, and 3 months after combined therapy.

Monotherapy reduced the average monthly migraine days from 28 to 18.6, for a difference of 9.4 days (p>0.0001). Initiation of combined therapy further decreased the monthly migraine days to 12.1 (p>0.0001).

“Combination therapy led to a reduction in total monthly migraine days of 15.8 [p> 0.0001],” reported Mays.

Importantly, 68 percent of patients reported a 50 percent or greater reduction in monthly migraine days. Forty-six percent said they had a 75 percent or greater reduction.

Expert insights

“The findings support what we see in clinical practice,” commented Dr Rashmi Halker Singh, associate professor of neurology at Mayo Clinic, Scottsdale in Arizona, US. “Single-agent treatment is not sufficient for many patients. There are preclinical data suggesting synergy, but insurance companies often deny claims on the pretext that combination agents are still experimental. Patients will then have to choose which drug they want to continue with, and that’s heartbreaking.”