No “Wearing‐Off Effect” Seen in Quarterly or Monthly Dosing of Fremanezumab: Subanalysis of a Randomized Long‐Term Study

Abstract

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.

Reducing the Burden of Migraine: Safety and Efficacy of CGRP Pathway-Targeted Preventive Treatments

“…For all monoclonal antibodies targeting the CGRP pathway, efficacy seen during 12 weeks of double-blind treatment was maintained during longer term treatment. An analysis of data from the fremanezumab long-term study in patients with CM or EM confirmed that there was no evidence of a “wearing-off” effect toward the end of dosing intervals with either quarterly or monthly dosing; there was no increase in the mean number of weekly migraine days between the first 2 weeks and last 2 weeks of quarterly or monthly dosing intervals throughout a total 15 months of treatment [ 42 ]. Similarly, an analysis of data from the 6-month EVOLVE-1 and -2 studies of galcanezumab in patients with EM and the 3-month REGAIN study of galcanezumab in patients with CM, showed no evidence of “wearing off” toward the end of the monthly dosing interval; reductions in migraine days during the first 2 weeks were comparable to those during the last 2 weeks of each month of treatment [ 43 ].…”

Tratamiento preventivo de la migraña con fremanezumab subcutáneo

“…Un estudio (n = 1.890) ha analizado específicamente esta cuestión seleccionando la variable días de migraña a la semana (DMS). Se realizaron las siguientes comparaciones en los meses 3, 6, 9 y 15 58 :…”

PEARL Study Protocol: a Real-World Study of Fremanezumab Effectiveness in Patients with Chronic or Episodic Migraine

“…In placebo-controlled clinical trials, fremanezumab treatment was associated with reduced headache frequency, severity and duration in patients with CM or EM, including patients with acute medication overuse and patients with difficult-to-treat migraine, such as those with inadequate response to 2-4 classes of migraine preventive medications [19][20][21][22][23]. In a long-term extension study following the pivotal 3-month studies of fremanezumab in CM and EM, efficacy was maintained for a further 12 months of treatment, with no evidence of wearing off at the end of the quarterly or monthly dose intervals [18,24]. Additionally, patients reported high levels of treatment satisfaction, as well as improvements in sleep quality, reduced anxiety and increased quality of time spent with others [25].…”