No 'Wearing-off Effect' Seen in Quarterly or Monthly Dosing of Fremanezumab: Sub-analysis of a Randomized Long-term Study.

Objective To evaluate whether quarterly or monthly administration of fremanezumab for migraine prevention exhibits a pattern of decreased efficacy towards 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 towards the end of the dosing interval.