The Journal of Headache and Pain | 2021
Shift from high-frequency to low-frequency episodic migraine in patients treated with Galcanezumab: results from two global randomized clinical trials
Abstract
Background Patients with episodic migraine (EM) with a higher-frequency of migraine headache days (HFEM: 8–14 migraine headache days/month) have a greater disease burden and a higher risk of progressing to chronic migraine (CM) with associated acute treatment overuse versus those with low-frequency EM (LFEM: 4–7 migraine headache days/month). In this post hoc analysis, we assessed the proportions of patients who shifted from HFEM to LFEM and to very low-frequency EM (VLFEM: 0–3 migraine headache days/month) status following treatment with galcanezumab versus placebo. Methods EVOLVE-1 and EVOLVE-2 were double-blind, Phase 3 studies in patients with EM. Patients (18–65\u2009years) were randomized (2:1:1) to subcutaneous monthly injections of placebo, galcanezumab 120\u2009mg (240\u2009mg loading dose) or 240\u2009mg, for up to 6\u2009months. Data were pooled and endpoints were change from baseline in number of migraine headache days/month and patients who shifted from HFEM to LFEM or VLFEM status. Impact of change in HFEM status on migraine headache days/month, quality of life and disability was also assessed. Results A total of 66% (1176/1773) patients from EVOLVE studies had HFEM status at baseline and were included in this analysis; placebo: 592, galcanezumab 120\u2009mg: 294 and galcanezumab 240\u2009mg: 290. At each month, both doses of galcanezumab resulted in a higher proportion of patients who shifted to 0–7 monthly headache days/month (VLFEM or LFEM status). Patients who shifted from HFEM at baseline to VLFEM status at Month 3, a relatively larger proportion of patients on galcanezumab 120\u2009mg versus placebo remained at VLFEM status at Months 4–6; Months 4–5 for galcanezumab 240\u2009mg versus placebo. Among the galcanezumab-treated patients who did-not-shift or shifted to LFEM or VLFEM status for ≥3 consecutive months until the end of the study, patients who shifted from HFEM to VLFEM status experienced the largest reduction in migraine headache days/month and the largest clinically meaningful improvements in daily functioning (MSQ-RFR) and disability (MIDAS). Conclusions In patients with HFEM, treatment with galcanezumab (120\u2009mg and 240\u2009mg) significantly reduced migraine headache days/month, maintained remission status at subsequent months until the end of the study, and improved patients’ quality of life versus placebo. Trial registration ClinicalTrials.gov Identifier: EVOLVE-1, NCT02614183 ; EVOLVE-2, NCT02614196 .