Fremanezumab for the Preventive Treatment of Migraine: Subgroup Analysis by Number of Prior Preventive Treatments with Inadequate Response

Abstract

Objective: To evaluate the efficacy of monthly or quarterly fremanezumab in patients with chronic migraine or episodic migraine and documented inadequate response to 2, 3, or 4 classes of prior migraine preventive medications.

Methods: This is an exploratory analysis of a randomized, double-blind, placebo-controlled, phase 3b trial for patients with chronic migraine or episodic migraine and inadequate response to 2 to 4 prior migraine preventive medication classes randomized (1:1:1) to fremanezumab (quarterly or monthly) or placebo. In this exploratory analysis, changes from baseline in the monthly average number of migraine days during 12 weeks of double-blind treatment and adverse events were evaluated for predefined subgroups of patients by number of prior preventive medication classes with inadequate response.

Results: Overall, 414, 265, and 153 patients had inadequate response to 2, 3, and 4 preventive medication classes, respectively. Changes from baseline in monthly average migraine days during 12 weeks were significantly greater with fremanezumab compared with placebo for patients with documented inadequate response to 2 classes (least-squares mean difference vs placebo [95% confidence interval]: quarterly, -2.9 [-3.83, -1.98]; monthly, -3.7 [-4.63, -2.75]), 3 classes (quarterly, -3.3 [-4.65, -1.95]; monthly, -3.0 [-4.25, -1.66]), and 4 classes (quarterly, -5.3 [-7.38, -3.22]; monthly, -5.4 [-7.35, -3.48]) of migraine preventive medications (all p < 0.001). No significant treatment-by-subgroup interactions were observed for any outcome (p interaction > 0.20 for all). Adverse events were comparable for placebo and fremanezumab.

Conclusion: Significant improvements in efficacy were observed with fremanezumab compared with placebo, even in patients who had previously experienced inadequate response to 4 different classes of migraine preventive medications.ClinicalTrials.gov identifier: NCT03308968.

Keywords: CGRP; Chronic migraine; episodic migraine; treatment failure.

Figure 1.

Change from baseline in monthly average migraine days over 12 weeks of treatment. (a) All patients (b) EM patients (c) CM patients. LSM, least-squares mean; EM, episodic migraine; CM, chronic migraine. ^ap < 0.001 versus placebo. ^bp = 0.011 versus placebo. ^cp = 0.007 versus placebo. ^dp = 0.003 versus placebo.

Figure 2.

Change from baseline in the monthly average number of migraine days over the first 4 weeks of treatment. LSM, least-squares mean. ^ap < 0.0001 versus placebo.

Figure 3.

ORs (fremanezumab vs placebo) for achieving ≥50% reduction in monthly migraine days. (a) Over 12 weeks of treatment (b) At 4 weeks of treatment. OR, odds ratio; CI, confidence interval. ^aClasses of migraine preventive medications.

Figure 4.

Proportion of PGIC responders. PGIC, Patient Global Impression of Change. PGIC responder was defined as a patient who reported a rating of 5 to 7 (moderately better, better, or a great deal better) on the PGIC. ^ap < 0.001 versus placebo.