Onset of efficacy and duration of response of galcanezumab for the prevention of episodic migraine: a post-hoc analysis

Abstract

Background and objective: As new migraine prevention treatments are developed, the onset of a preventive effect, how long it is maintained and whether patients initially non-responsive develop clinically meaningful responses with continued treatment can be assessed.

Methods: Analyses were conducted post-hoc of a double-blind, placebo-controlled, phase II-a study in patients with episodic migraine receiving galcanezumab 150 mg or placebo biweekly for 12 weeks (Lancet Neurol 13:885, 2014). The number of migraine headache days per week, and onset of efficacy measured as the first week galacanezumab separated from placebo were determined. Patients with ≥50%, ≥75% and 100% reduction in migraine headache days from baseline at months 1, 2 and 3 were calculated and defined as sustained responses. Non-responders (<50% response) at month 1 or 2 who then showed ≥50%, ≥75% and 100% response at later time-points were calculated.

Results: Patients were randomised to galcanezumab (n=107) or placebo (n=110). A significant (p=0.018) change of -0.89±0.11 (galcanezumab) vs -0.53±0.11 (placebo) migraine headache days indicated onset at week 1. Forty-seven per cent of galcanezumab and 25% of placebo patients responding at month 1 maintained response through months 2 and 3. Of non-responders at month 1, 27% on galcanezumab and 20% on placebo responded on months 2 and 3, and 50% of galcanezumab non-responders in months 1 and 2 responded on month 3, vs 24% on placebo.

Conclusions: The onset of efficacy of galcanezumab is within 1 week in a majority of patients, and patients receiving galcanezumab are twice more likely to maintain responses than placebo patients. Early non-responders may respond by month 2 or month 3.

Trial registration number: NCT01625988.

Keywords: CGRP; LY2951742; calcitonin gene-related peptide; clinical trial; galcanezumab; migraine.

Figure 1

Study design. *Washout period of 30 days was included for patients to discontinue the use of migraine prevention medications. Patients who did not need a washout period were moved to the baseline period as soon as study eligibility was verified. ^†Eligible patients who met all the inclusion criteria and none of the exclusion criteria continued with the study.

Figure 2

(A) Change from baseline in weekly MHD±SE. (B) Change from baseline in weekly MHD or probable MHD±SE. *P<0.05. LS, least square; MHD, migraine headache days.

Figure 3

Sustained response^† of galcanezumab-treated (n=99) versus placebo-treated (n=105) patients for months 1, 2 and 3. *P<0.05. ^†Sustained response is defined as the proportion of patients with ≥50%, ≥75% and ≥100% reduction in migraine headache days from baseline at month 1 and who sustained those same response levels through months 2 and 3.

Figure 4

Proportion of galcanezumab-treated (n=41) versus placebo-treated (n=61) patients not meeting ≥50% response (ie, ≥50% improvement from baseline in migraine headache days) at month 1 but meeting ≥50%, ≥75% and 100% response at months 2 and 3. *P<0.05.

Figure 5

Proportion of galcanezumab-treated (n=22) versus placebo-treated (n=46) patients not meeting ≥50% response (ie, ≥50% improvement from baseline in migraine headache days) at months 1 and 2 but meeting ≥50%, ≥75% and 100% response at month 3. *P<0.05.