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 years) were randomized (2:1:1) to subcutaneous monthly injections of placebo, galcanezumab 120 mg (240 mg loading dose) or 240 mg, for up to 6 months. 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 mg: 294 and galcanezumab 240 mg: 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 mg versus placebo remained at VLFEM status at Months 4-6; Months 4-5 for galcanezumab 240 mg 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 mg and 240 mg) 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 .

Keywords: Episodic migraine; MIDAS; MSQ-RFR; Migraine frequency; QoL; Sustained improvement.

Conflict of interest statement

Jakub Jedynak, Virginia L. Stauffer, Mallik Rettiganti are employees of Eli Lilly and Company and/or its subsidiaries and hold company stock. Dr. Gendolla receives fees for ad boards, lectures and participation in clinical trials from Pharm Allergan, Reckitt Benckiser, Bayer, Grünenthal, Mundipharma, Novartis, Eli Lilly and Company, Teva, Sanofi and Hormosan. Eric Eross is a consultant and is a member of the speaker bureau at Eli Lilly and Company.

Figures

Fig. 1

Percentage of HFEM patients at baseline receiving galcanezumab (versus placebo) and shifting from HFEM status to LFEM status, or HFEM to VLFEM status at each month during the treatment period. Abbreviations: GMB, galcanezumab; HFEM, high-frequency episodic migraine; LFEM, low-frequency episodic migraine; n, number of patients who were categorized as HFEM at baseline with a baseline value and at least one post-baseline value recorded; VLFEM, very low-frequency episodic migraine. Note: The percentages shown in the figure are raw values at each month and treatment group. P values comparing galcanezumab vs placebo are from the following GLIMMIX model for repeated measures: Shift from HFEM to VLFEM indicator = baseline migraine headache days/month, treatment group, month, treatment x month interaction, and study indicator (EVOLVE-1 and EVOLVE-2)

Fig. 2

Percentage of patients who achieve VLFEM at Month 3 and (a) maintained VLFEM status at each of Months 4, 5 or 6, (b) maintained VLFEM status across Months 4, 5 or 6. Abbreviations: CI, confidence interval; GMB, galcanezumab; HFEM, high-frequency episodic migraine; n, number of patients who were categorized as HFEM at baseline with a baseline value and at least one post-baseline value recorded; OR, odds ratio; VLFEM, very low-frequency episodic migraine

Fig. 3

Percentage of patients shifting from HFEM to VLFEM status anytime during the double-blind treatment period and maintaining their shift from HFEM status to VLFEM status for ≥ 3 consecutive months until the end of the study (patients with HFEM at baseline). ***P < .001 versus placebo from logistic regression analysis. Abbreviations: CI, confidence interval; GMB, galcanezumab; HFEM, high-frequency episodic migraine; n, number of patients who were categorized as HFEM at baseline with a baseline value and at least one post-baseline value recorded; OR, odds ratio; VLFEM, very low-frequency episodic migraine

Fig. 4

Change from baseline to Month 6 in HFEM patients receiving galcanezumab who 1) did not shift, 2) shifted to LFEM or 3) VLFEM for ≥ 3 consecutive months until the end of the study for (a) migraine headache days/month, (b) MSQ-RFR score and (c) MIDAS total score. All P < .001 shift from ‘HFEM status to LFEM status’ versus ‘no shift’ and to ‘VLFEM status’ versus ‘no shift’. The between group comparisons for migraine headache days/month (panel a) were done using ANOVA with raw mean changes and standard deviation shown, whereas MSQ (panel b) and MIDAS (panel c) were analyzed using ANCOVA models adjusted for covariates with estimated least squares means and standard errors displayed. Abbreviations: ANOVA, Analysis of Variance; ANCOVA, Analysis of Covariance; BL, baseline; GMB, galcanezumab; HFEM, high-frequency episodic migraine; HFEM, low-frequency episodic migraine; MIDAS, Migraine Disability Index, MSQv2.1 RFR, Migraine-Specific Questionnaire Version 2.1 Role Function Restrictive, VLFEM, very low-frequency episodic migraine