Real-World Insights into Dual Calcitonin Gene-Related Peptide (CGRP) Therapies for Chronic Migraine: A Retrospective Review.

Abstract

Patients on regimens of a single calcitonin gene-related peptide (CGRP) may show a delayed response to migraine symptoms. Individuals on such regimens may not even exhibit a reduction of migraine symptoms within a reasonable time frame. Some clinicians have elected to combine small-molecule antagonists (SMAs) and ligand monoclonal antibodies (L-mAbs) to target CGRP molecules and receptors for the purpose of potentially providing increased synergistic relief. This study aimed to compare the safety and effectiveness of dual-CGRP therapy for patients receiving combined synergistic SMA and L-mAb to the safety and effectiveness of mono-CGRP treatment. A retrospective matched cohort study. This study was conducted at a single neurological center in the United States. A retrospective matched cohort study at a neurological care center analyzed 90 chronic migraine patients who were aged >= 18 years and treated with CGRP inhibitors (L-mAbs: fremanezumab, galcanezumab, eptinezumab; SMAs: ubrogepant, rimegepant, atogepant; or a combination) between May 2018 and February 2024. The study compared 27 patients receiving dual L-mAb and SMA CGRP treatments with 63 patients receiving mono-L-mAb or mono-SMA CGRP treatments, matched by age and gender. Variables included current age, age at diagnosis, gender, onabotulinumtoxinA use, headache frequency, duration, severity, and associated symptoms before the treatment and 3 months after it. Adverse events were recorded for both treatment groups. All hypothesis tests were two-tailed and considered significant at a P-value < 0.05. Dual-CGRP therapy reduced headache severity by 20%, in contrast to the 10% reduction seen with mono-CGRP therapy (P = 0.039). Patients receiving dual-CGRP therapy also experienced an average reduction of 4 headache days, with some patients experiencing up to 14 fewer days, while mono-CGRP patients showed no change; however, this finding was not statistically significant (P = 0.112). No significant differences in other migraine-associated symptoms were found between the groups. Adverse events in the mono- and dual-CGRP groups were mild, with no serious adverse events or discontinuations reported. Limitations of our study include a relatively small sample size, the study's retrospective design, the absence of newer CGRP agents, an inability to control confounders, and the predominant use of a few CGRP inhibitors among patients. Dual-CGRP regimens may enhance migraine symptom control by reducing headache severity without causing significant adverse events. However, these findings need confirmation through randomized, placebo-controlled clinical trials that use larger sample sizes.