37 - Clinically Meaningful Responses to Fremanezumab in Migraine Patients With Medication Overuse and Documented Inadequate Response to 2-4 Migraine Preventive Medications in the Randomized, Placebo-controlled FOCUS Study
1Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 2Teva Pharmaceuticals Industries, West Chester, PA, USA. 3Boston Headache Institute, Boston PainCare, Waltham, MA, USA
Purpose Patients who overuse acute medications for migraine generally experience a greater disease burden, including more 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 chronic migraine (CM) or episodic migraine (EM) and documented inadequate response to 2 to 4 classes of migraine preventive medications. We aimed to evaluate responder rates in a subgroup of patients with medication overuse (use of any acute medication on ≥15 days/month or use of triptans, ergots, or combination medications on ≥10 days/month) at baseline. Methods For 12 weeks of double-blind treatment in the randomized, double-blind, placebo-controlled period of the phase 3b FOCUS study, patients were randomized (1:1:1) to quarterly fremanezumab (months 1/2/3: 675 mg/placebo/placebo), monthly fremanezumab (months 1/2/3: 225 mg [EM],675 mg [CM]/225 mg/225 mg), or matched monthly placebo. Proportions of patients with ≥50% and ≥75% reductions from baseline in the monthly average number of migraine days at 4 weeks and during 12 weeks were compared using logistic regression. Results Of 838 randomized patients, 435 had medication overuse. During 12 weeks of double-blind treatment, a significantly greater proportion of patients achieved ≥50% reduction in the monthly average number of migraine days with quarterly fremanezumab (25%) and monthly fremanezumab (33%) versus placebo (7%; P≤0.0001). A significantly greater proportion of patients also achieved ≥75% reduction in the monthly average number of migraine days with monthly fremanezumab (11%) versus placebo (1%; P= 0.0040) during 12 weeks of treatment; differences between quarterly fremanezumab (5%) and placebo were not statistically significant. At 4 weeks, significantly greater proportions of patients achieved ≥50% and ≥75% reduction in the monthly average number of migraine days with both fremanezumab dosing regimen versus placebo (P≤0.0125). Conclusions In migraine patients with medication overuse and documented inadequate response to 2 to 4 classes of migraine preventive medication classes, significantly more patients treated with fremanezumab achieved ≥50% and 75% reductions in the monthly average number of migraine days versus placebo. Fremanezumab provided early and sustained clinically meaningful results in this subgroup, suggesting medication overuse is not an impediment to effective preventive treatment with this antibody.