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.

Conflict of interest statement

Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LP declares no conflict of interest. JMC, XN, and VRC are employees of Teva Pharmaceuticals. RY is a former employee of Teva Pharmaceuticals. PPR has received honoraria as a consultant and speaker for Allergan, Almirall, Biohaven, Chiesi, Eli Lilly, Medscape, Neurodiem, Novartis, and Teva Pharmaceuticals. Her research group has received research grants from AGAUR, Allergan, la Caixa Foundation, FP7, Instituto de Salud Carlos III, Migraine Research Foundation, MICINN, and PERIS; and has received funding in the last 5 years for clinical trials from Alder, electroCore, Eli Lilly, Novartis, and Teva Pharmaceuticals. She does not own stocks from any pharmaceutical company.

Figures

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.