Galcanezumab Provides Consistent Efficacy Throughout the Dosing Interval Among Patients with Episodic and Chronic Migraine: A Post Hoc Analysis

Abstract

Introduction: The consistency of the treatment effect of galcanezumab throughout the dosing interval is examined in patients with episodic and chronic migraine.

Methods: This study was a post hoc analysis of clinical trial data from episodic (EVOLVE-1; EVOLVE-2; both 6-month duration) and chronic (REGAIN; 3-month duration) migraine double-blind trials evaluating the efficacy of a once-monthly injection of galcanezumab 120 mg relative to placebo. Adults with episodic (placebo, n = 894; galcanezumab, n = 444) or chronic migraine (placebo, n = 558; galcanezumab, n = 278) were included. Mean change from baseline in weekly migraine headache days, averaged across all months for each week of the dosing interval, was compared between groups and within the galcanezumab group during weeks 1 and 4. Additional analyses examined the mean difference from placebo in weekly migraine headache days and a day-by-day analysis.

Results: Weekly migraine headache day reduction was significantly greater with galcanezumab relative to placebo every week (P < 0.001) and did not differ during weeks 1 and 4 for those with episodic (P = 0.740) or chronic migraine (P = 0.231) taking galcanezumab. Estimated probabilities of migraine on day 2 and day 30 did not differ for those with episodic (P = 0.61) or chronic migraine (P = 0.616) taking galcanezumab.

Conclusion: This analysis demonstrates once monthly galcanezumab exhibits consistent efficacy throughout the dosing interval among the population of patients with migraine in three clinical trials evaluating the efficacy of galcanezumab. There is no evidence from these trials that the effect of galcanezumab "wears off" at the end of the dosing interval.

Trial registration: ClinicalTrials.gov identifier: EVOLVE-1 (NCT02614183); EVOLVE-2 (NCT02614196); REGAIN (NCT02614261).

Keywords: Chronic; Efficacy; Episodic; Galcanezumab; Migraine; Wear off.

Fig. 1

Episodic migraine: LS mean change from baseline in weekly migraine headache days across all months (EVOLVE-1 and EVOLVE-2 pooled). ^aP < 0.001 versus placebo based on MMRM analysis. Mean changes from baseline for each treatment group were estimated using an MMRM model for repeated measures after adjusting for baseline migraine headache days, week, month, study, pooled region/country (nested within study), and the treatment-by-week and baseline-by-week interaction effects. GMB galcanezumab, LS least-squares, MMRM mixed-model repeated measures, SE standard error

Fig. 2

Episodic migraine: estimated probability of migraine by day averaged across all 6 months (EVOLVE-1 and EVOLVE-2 pooled). ^aP ≤ 0.001 versus placebo (P values comparing probability of migraine between the two groups was significant for all days). Probabilities shown for each treatment group were estimated using a generalized linear mixed-effects model for repeated measures adjusting for baseline migraine headache days, day, month, study, and treatment-by-day interaction effect. GMB galcanezumab

Fig. 3

Chronic migraine: LS mean change from baseline in weekly migraine headache days across all months (REGAIN) for each treatment group. ^aP < 0.001 versus placebo based on MMRM analysis. Mean changes from baseline for each treatment group were estimated using an MMRM model for repeated measures after adjusting for baseline migraine headache days, week, month, pooled region/country, and the treatment-by-week and baseline-by-week interaction effects. GMB galcanezumab, LS least squares, MMRM mixed-model repeated measures, SE standard error

Fig. 4

Chronic migraine: estimated probability of migraine by day averaged across all 3 months (REGAIN). ^aP ≤ 0.001 versus placebo, ^bP ≤ 0.010 versus placebo, ^cP < 0.050 versus placebo. Probabilities shown for each treatment group were estimated using a generalized linear mixed-effects model for repeated measures adjusting for baseline migraine headache days, day, month, and treatment-by-day interaction effect. GMB galcanezumab