The Safety and Effectiveness of Dual Calcitonin Gene-Related Peptide (CGRP) Therapies for Migraine Treatment: A Focus on Small Molecule Antagonist and Ligand Monoclonal Combinations
Ho Hyun Lee1, Anita Cheung1, Anson Lee1, Julia Jahansooz1, Edward Weldon1, Kyle Ishikawa1, Reyn Yoshioka2, Man Ian Woo2, Lana Liquard2, Enrique Carrazana2, Kore Liow2
1University of Hawaii John A. Burns School of Medicine, 2Headache & Facial Pain Center, Hawaii Pacific Neuroscience
Objective:

To assess the effects of dual-CGRP therapy on patients with synergistic use of small molecule antagonists (SMA) and ligand monoclonal antibodies (L-mAb).

Background:

Single CGRP regimens may not improve migraine outcomes and could worsen symptoms in some patients. Combining SMAs and L-mAbs targets CGRP molecules and receptors, potentially providing increased synergistic relief. Our study aims to assess the effects of this dual-CGRP approach.

Design/Methods:

A retrospective matched cohort study was conducted at a neurological care center in Hawaii, analyzing 90 chronic migraine patients aged ≥18 years treated with CGRP inhibitors (L-mAbs: fremanezumab, galcanezumab, eptinezumab; SMAs: ubrogepant, rimegepant, atogepant; or a combination). The study compared dual L-mAb and SMA CGRP treatments with mono-L-mAb or mono-SMA CGRP treatments, matched by age and sex. Variables included age, age at diagnosis, sex, onabotulinumtoxinA use, headache frequency, duration, severity, and associated symptoms before and three months post-treatment. Adverse events were recorded for the dual-treatment group at three-month follow-up. Statistical analyses were made using Wilcoxon, Kruskal-Wallis, and Fisher's exact tests, with significance set at < 0.05.

Results:

Patients on dual-CGRP therapy had an average reduction of four headache days, with some experiencing up to 14 fewer days, while mono-CGRP patients experienced no change (p = 0.112). Headache severity was reduced by 20% for dual-CGRP patients and 10% for mono-CGRP patients (p = 0.039). Aura symptoms were significantly reduced in the dual-CGRP group, with 48% (13 patients) becoming aura-free compared to 20% in the mono-CGRP group (p = 0.004). Adverse events in the dual-CGRP group were mild, with three patients experiencing fatigue, drowsiness, or mild constipation. No patients discontinued treatment, and no serious adverse events were reported.

Conclusions:

Dual-CGRP regimens may provide improved effectiveness for controlling migraine symptoms by significantly reducing headache severity and aura symptoms without significant adverse events.

10.1212/WNL.0000000000208371
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.