Background Single CGRP regimens may not improve migraine outcomes and could worsen symptoms in some patients. Combining small molecule antagonists (SMA) and ligand monoclonal antibodies (L-mAb) targets CGRP molecules and receptors, potentially providing increased synergistic relief. Our study aims to assess the effects of this dual-CGRP approach.

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.

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