BACKGROUND: Patients with high-frequency episodic migraine (HFEM) have a greater 
disease burden than those with low-frequency episodic migraine (LFEM). Acute 
treatment overuse increases the risk of migraine chronification in patients with 
HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin 
gene-related peptide (CGRP), is effective for migraine prevention with a 
favorable safety profile. Here, we investigate whether there are differences in 
galcanezumab efficacy in patients with LFEM or with HFEM.
METHODS: Data were pooled from two double-blind, placebo-controlled phase 3 
trials; EVOLVE-1 and EVOLVE-2. Patients were 18-65 years old, experienced 4-14 
monthly migraine headache days (MHDs) for ≥1 year prior, with onset at 
< 50 years of age. Migraine headaches were tracked via electronic 
patient-reported outcome system and randomization was stratified by low (LFEM; 
4-7 monthly MHDs) or high (HFEM; 8-14 monthly MHDs) frequency. Subgroup analysis 
compared the HFEM and LFEM subgroups with a linear or generalized linear mixed 
model repeated measures approach.
RESULTS: The intent-to-treat patients (N = 1773) had a mean age of 41.3 years, 
were mostly white (75%), female (85%), and 66% of patients had HFEM. In both the 
LFEM and HFEM subgroups, the overall (Months 1-6) and monthly changes from 
baseline in monthly MHDs and monthly MHDs with acute medication use compared 
with placebo were statistically significantly reduced for galcanezumab 120-mg 
and 240-mg. Galcanezumab (120-mg and 240-mg) significantly decreased the overall 
and monthly MHDs with nausea and/or vomiting, and with photophobia and 
phonophobia versus placebo in patients with LFEM or HFEM. In both subgroups, the 
mean overall (Months 1-6) and monthly percentages of patients with ≥50%, ≥75%, 
and 100% reduction in monthly MHDs from baseline were statistically 
significantly greater in patients receiving either dose of galcanezumab versus 
placebo. Galcanezumab (120-mg and 240-mg) significantly improved the 
Migraine-Specific Quality of Life Questionnaire role function-restrictive domain 
score as well as the Migraine Disability Assessment total score versus placebo 
for patients with LFEM or HFEM. There were no significant subgroup-by-treatment 
interactions.
CONCLUSIONS: Galcanezumab was as effective in patients with HFEM as in those 
with LFEM. Associated symptoms, quality of life, and disability were similarly 
improved in patients with HFEM or LFEM.
TRIAL REGISTRATION: NCT02614183 , NCT02614196 .