40 - Efficacy of Fremanezumab in Migraine Patients with Medication Overuse and Documented Inadequate Response to 2-4 Migraine Preventive Medication Classes: Subgroup Analysis of the Randomized, Placebo-controlled FOCUS Study
Stephen Silberstein1, Joshua M. Cohen2, Verena Ramirez Campos2, Ronghua Yang2, Maja Galic3, Xiaoping Ning2, Adelene Jann4
1Jefferson Headache Center, Philadelphia, PA, USA. 2Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA. 3Teva Pharmaceuticals, Amsterdam, Netherlands. 4NYU Langone Health, New York, NY, USA
Purpose Patients who overuse acute medicationsfor migraine generally experience more migraine days, greater disability, and more severe pain intensity. 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 both chronic migraine (CM) and episodic migraine (EM) and documented inadequate response to 2 to 4 classes of migraine preventive medications.This subgroup analysis of the FOCUS study evaluated the efficacy of fremanezumab in patients with baseline medication overuse (use of any acute medication on ≥15 days/month or use of triptans, ergots, or combination medications on ≥10 days/month). 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: CM, 675 mg; EM, 225 mg; months 2 and 3: 225 mg), or matched monthly placebo for 12 weeks. Changes from baseline in the monthly average number of migraine days and monthly average number of headache days of at least moderate severity at 4 weeks and during 12 weeks of treatment were compared using a mixed-effect model for repeated measures. Results Of 838 randomized patients, 435 had baseline medication overuse. Reductions from baseline in the monthly average number of migraine days were significantly greater with quarterly fremanezumab (least-squares mean [standard error (SE)] change, −3.3 [0.61]) and monthly fremanezumab (−4.6 [0.55]) versus placebo (−0.5 [0.62]; both P≤0.0001) during 12 weeks of treatment. Reductions from baseline in the monthly average number of headache days of at least moderate severity were also significantly greater with quarterly fremanezumab (least-squares mean [SE] change, −4.0 [0.61]) and monthly fremanezumab (−5.1 [0.54]) versus placebo (−0.8, [0.61]; both P<0.0001) during 12 weeks of treatment. At 4 weeks of double-blind treatment, changes from baseline in the monthly average number of migraine days and monthly average number of headache days of at least moderate severity were also significantly greater with both dosing regimens of fremanezumab versus placebo (all P<0.0001). Conclusions Quarterly and monthly fremanezumab provided early and sustained reductions in monthly migraine and monthly headache days of at least moderate severity versus placebo in migraine patients with medication overuse and documented inadequate response to 2 to 4 classes of migraine preventive medications.