39 - Early Onset of Efficacy With Fremanezumab in Patients With Medication Overuse and Documented Inadequate Response to 2-4 Classes of Migraine Preventive Treatments: Subgroup Analysis of the Randomized, Double-blind FOCUS Study

¹Department of Neurology, University of Duisburg-Essen, Essen, Germany. ²CCR Czech Prague, Prague, Czech Republic. ³Teva Pharmaceuticals Industries, West Chester, PA, USA. ⁴Boston Headache Institute, Boston PainCare, Waltham, MA, USA

Purpose
The overuse of acute medications for migraine is often associated with a greater disease burden, including a greater number of migraine days, more severe pain intensity, and greater disability. The FOCUS study of fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), was the first and largest study of a migraine preventive treatment in adults with either chronic migraine (CM) or episodic migraine (EM) and documented inadequate response to 2 to 4 classes of migraine preventive medications. Early response was evaluated in a subgroup of patients with CM or EM and medication overuse (use of any acute medication ≥15 days/month or use of triptans, ergots, or combination medications ≥10 days/month) at baseline.
Methods
In the randomized, double-blind, placebo-controlled period of the phase 3b FOCUS study, patients were randomized (1:1:1) to quarterly fremanezumab (Month 1: 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: EM, 225 mg; CM, 675 mg; months 2 and 3: 225 mg), or matched monthly placebo for 12 weeks. At weeks 1 to 3, changes from baseline in the weekly average number of migraine days and weekly average number of headache days of at least moderate severity were evaluated using mixed-effects models for repeated measures, and responder rates (≥50% reduction in the weekly average number of migraine days) were evaluated using logistic regression.
Results
Of 838 randomized patients, 435 had medication overuse. Reductions from baseline in weekly migraine days were significantly greater with fremanezumab versus placebo by Week 1 (least-squares mean [standard error] change from baseline: quarterly fremanezumab, −0.9 [0.20]; monthly fremanezumab, −1.2 [0.18] vs placebo, −0.1 [0.21]; P≤0.0018), as were reductions in weekly headache days of at least moderate severity (quarterly fremanezumab, −1.0 [0.20]; monthly fremanezumab, −1.4 [0.18] vs placebo, −0.1 [0.20]; P≤0.0003). Significantly higher proportions of patients achieved ≥50% reductions in migraine days with fremanezumab versus placebo at Week 1 (quarterly fremanezumab, 39%; monthly fremanezumab, 38% vs placebo, 14%; P<0.0001). Significant differences were maintained through Weeks 2 and 3 (all P≤0.0004).
Conclusions
Both quarterly and monthly fremanezumab demonstrated early onset of action, with greater response rates within 1 week and significantly greater reductions in weekly migraine days and headache days as early as week 1 versus placebo, in migraine patients with medication overuse and documented inadequate response to 2 to 4 classes of migraine preventive medications.