Lack of “wearing off” effect with eptinezumab in the preventive treatment of migraine
Roger Cady1, Meghana Karnik-Henry2, Divya Asher2, Seema Soni-Brahmbhatt2, David W Dodick3
1RK Consults, 2Lundbeck LLC, 3Mayo Clinic College of Medicine
Objective:
To demonstrate the lack of a “wearing off effect” with eptinezumab in preventive migraine treatment.
Background:
A “wearing off effect” is described as a positive response to treatment with a shorter duration of benefit than expected.
Design/Methods:
PROMISE-1 (NCT02559895) and PROMISE-2 (NCT02974153) were both phase 3, randomized, double-blind, placebo-controlled studies that evaluated the efficacy and safety of eptinezumab (administered every 12 weeks) for migraine prevention in adults with episodic or chronic migraine, respectively. PROMISE-1 and PROMISE-2 captured monthly migraine days (MMDs) for up to 48 weeks and 24 weeks of treatment, respectively. Using data on the change in MMDs, a post hoc closed testing analysis investigated the consistency of effect during the first dosing interval. The percentage of patients experiencing a migraine attack at intervals reduced by a single day was analyzed beginning with the primary endpoint interval (Weeks 1-12, or Days 1-84).
Results:
In both studies, eptinezumab 100mg and 300mg demonstrated greater reductions vs placebo in MMDs over 4-week intervals that were sustained across the respective treatment periods. The closed testing analysis showed that both doses achieved nominally significant differences (P<0.05) from Day 84 to Day 1 independently, indicating that eptinezumab was effective beginning Day 1 after dosing. Reductions from baseline were greater than the reduction for placebo across the entire curve. Similar magnitudes of effect over each 4-week interval at the population level suggests the onset of the migraine preventive effect of eptinezumab can be observed on Day 1 following initial dosing, with the effect sustained through the full 12 weeks.
Conclusions:
No statistically significant differences were found between the percentages of patients reporting migraine attack reduction on Day 1 and on any day through Day 84. In both pivotal trials for eptinezumab, there is no significant “wearing off” of eptinezumab’s preventive benefit observed through Day 84.