No Significant Wearing Off Effect With Galcanezumab for Migraine Prevention

A post-hoc analysis of 4 clinical trials of galcanezumab found no differences between dose groups of galcanezumab or placebo in rates of ‘wearing off’ effect.

Recent data from a post-hoc analysis of several studies of galcanezumab in people with migraine suggest that rates of individual patients meeting the threshold of “wearing off” of treatment efficacy were low with no statistically significant differences observed among placebo and galcanezumab dose groups.

These findings were presented at the 2021 Virtual American Headache Society (AHS) 63rd Annual Scientific Meeting, June 3-6, by Jessica Ailani, MD, FAHS, FAAN, director, MedStar Georgetown Headache Center. “Prior analysis showed that there was no wearing off with galvanism at the population level. However, there have been anecdotal reports suggesting that some patients may experience an increase in migraine headache frequency as their calcitonin gene-related peptide (CGRP) monoclonal antibody treatment wears off,” Ailani said during her presentation. 

Ailani and colleagues analyzed individual patient-level data from 4 double-blind, placebo-controlled phase 3 studies: EVOLVE-1 (NCT02614183; n = 1176) and EVOLVE-2 (NCT02614196; n = 1176) of high frequency episodic migraine (EM), REGAIN (NCT02614261; n = 1113) of chronic migraine (CM), and CONQUER (NCT03559257; n = 391) of CM and EM. 

Patients received monthly subcutaneous galcanezumab 120 mg (with 240-mg loading dose; n = EVOLVE 1/2, 257; CONQUER, 101 EM, 89 CM; REGAIN, 257), galcanezumab 240 mg (n = EVOLVE 1/2, 253; REGAIN, 261), or placebo (n = EVOLVE 1/2, 502; CONQUER 93 EM, 95 CM; REGAIN, 501). “Wearing off” was defined by an increase of at least 2 migraine headache days per week from Week 2 to Week 4 (the 7 days prior to next dose) during at least 2 months of months 4-6 in EVOLVE-1 and -2, or during both months 2 and 3 in REGAIN and CONQUER.

READ MORE: Total Migraine Pain Burden Reduced With Galcanezumab in Post-Hoc Analysis

Participants had a mean age of 41.0 (standard deviation [SD], 11.4) in the EVOLVE trials, 45.5 (SD, 11.4) in the EM group and 45.3 (SD, 12.4) in the CM group in CONQUER, and 41.0 (SD, 12.1) in REGAIN. Participants were mostly women across all trials (EVOLVE, 86.6%; CONQUER EM, 85.9%; CONQUER CM, 87.1%; REGAIN, 85.0%). 

The investigators found that rates of wearing off in EM populations were comparable among placebo and galcanezumab-treated patients, with 4% to 7% of patients meeting the predefined criteria. In the EVOLVE trials, in which 3 months of data were available, less than 1% of patients met the criteria during all 3 months.

In patients with CM, the rates of wearing off were slightly higher in galcanezumab-treated patients versus placebo, with 3% to 9% of all patients meeting the criteria. No statistically significant differences were seen between galcanezumab- and placebo-treated patients or galcanezumab dose groups in rates of wearing off (all P >.005).

“In conclusion, rates of individual patients meeting the threshold of wearing off in this post-hoc analysis were low, and no statistically significant difference was seen among the placebo, galcanezumab 120 mg, and galcanezumab 240 mg treatment arms,” Ailani said in her presentation.

Additionally, Ailani and coauthors stated limitations on their poster that include excluding patients with low frequency EM and only counting frequency of migraine headache days and not severity and attack duration in the definition of wearing off.

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Ailani J, Kuruppu D, Rettiganti M, et al. Does wearing off of efficacy occur in galcanezumab-treated patients at the end of the monthly treatment cycle: A post hoc analysis of four phase 3 randomized trials. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P65