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No "Wearing-Off Effect" Seen in Quarterly or Monthly Dosing of Fremanezumab: Subanalysis of a Randomized Long-Term
Andrew M Blumenfeld1, Darko M Stevanovic2, Mario Ortega2
1The Headache Center of Southern California, The Neurology Center, Carlsbad, CA, USA.
Objective:
To evaluate whether quarterly or monthly administration of fremanezumab for migraine prevention exhibits a pattern of decreased efficacy toward the end of the dosing interval (wearing-off effect).
Background:
The main goals of migraine preventive treatment are to reduce the frequency, severity, and duration of migraine attacks, and migraine-associated disability. Wearing-off refers to the phenomenon whereby clinical symptoms return or worsen before the next dose of a drug is due and has been reported previously with migraine preventive medications.
Design And Methods:
This was a long-term, 12-month, multicenter, randomized, double-blind, parallel-group phase 3 study (NCT02638103) that included chronic (CM) and episodic migraine (EM) patients who rolled over from the 12-week phase 3 HALO CM (NCT02621931) and EM trials (NCT02629861), as well as an additional subset of 312 new patients. Patients with CM or EM received fremanezumab either monthly or quarterly. In this post hoc analysis, for selected months, the difference in the average number of migraine days between weeks 1-2 and weeks 3-4, between weeks 1-3 and week 4, and between weeks 1-2 and weeks 11-12 were calculated.
Results:
A total of 1890 patients (CM, 1110; EM, 780) were enrolled. At months 3, 6, 9, and 15, there were no substantial differences in mean weekly migraine days between weeks 1-2 and weeks 3-4 or between weeks 1-3 and week 4 with quarterly or monthly fremanezumab in the CM or EM subgroups. There were no substantial increases in mean weekly migraine days between weeks 1-2 and weeks 11-12 during the first quarter of treatment (months 1-3) or the second quarter of treatment (months 4-6) with quarterly or monthly fremanezumab in the CM or EM subgroups. Across both dosing subgroups in CM and EM patients, the mean weekly number of migraine days decreased substantially (30%-42%) during the first 2 weeks; decreases in weekly migraine days remained steady during the last 2 weeks of the first quarter, with a similar maintenance of response during the second quarter.
Conclusions:
This analysis of data from a long-term, phase 3 study showed that patients receiving quarterly fremanezumab or monthly fremanezumab did not experience a wearing-off effect toward the end of the dosing interval.
Insights
Fremanezumab, administered quarterly or monthly, effectively prevents migraines without a decrease in efficacy towards the end of the dosing interval. This study confirms consistent migraine prevention for both chronic and episodic migraine patients.
Area of Science:
- Neurology
- Clinical Pharmacology
Background:
- Migraine prevention aims to reduce attack frequency, severity, duration, and associated disability.
- The wearing-off effect, a decline in efficacy before the next dose, is a concern with some migraine preventives.
Purpose of the Study:
- To assess if fremanezumab's efficacy diminishes towards the end of its dosing interval (quarterly or monthly) in migraine prevention.
- To investigate the presence of a wearing-off effect with fremanezumab in chronic migraine (CM) and episodic migraine (EM) patients.
Main Methods:
- A 12-month, randomized, double-blind, phase 3 study (NCT02638103) involving CM and EM patients.
- Patients received either quarterly or monthly fremanezumab, with some being new enrollees and others rolling over from prior trials.
- A post hoc analysis compared migraine days in the early versus late weeks of the dosing interval.
Main Results:
- No substantial differences in mean weekly migraine days were observed between early and late weeks of the dosing interval for either quarterly or monthly fremanezumab.
- No significant increases in migraine days were noted towards the end of the dosing interval across the first two quarters of treatment.
- A consistent reduction in mean weekly migraine days (30%-42%) was observed throughout the treatment period.
Conclusions:
- Quarterly and monthly fremanezumab administration did not result in a wearing-off effect in patients with chronic or episodic migraine.
- The study demonstrates sustained efficacy of fremanezumab regardless of the dosing frequency within the evaluated intervals.
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