Autor:innen:
Peter McAllister | New England Institute for Clinical Research | United States
Dr. Mareike Caesar | Teva GmbH | Germany
Ronghua Yang | Teva Pharmaceuticals | United States
Joshua Cohen | Teva Pharmaceuticals | United States
OBJECTIVES: The International Classification of Headache Disorders, third edition (beta version) (ICHD-3 beta) criteria for migraine include nausea, vomiting, photophobia, and phonophobia symptoms. Fremanezumab, a fully humanized monoclonal antibody (IgG2a) that selectively targets calcitonin gene-related peptide (CGRP), reduced the frequency and severity of headaches in patients with chronic migraine (CM). We assessed the effect of fremanezumab versus placebo on nausea or vomiting, and photophobia and phonophobia, in patients with CM.
METHODS: In this multicenter, randomized, double-blind, placebo-controlled, Phase 3 study, patients with CM were randomized 1:1:1 to receive subcutaneous injections of fremanezumab quarterly (675 mg at baseline, placebo at Weeks 4 and 8), fremanezumab monthly (675 mg at baseline, 225 mg at Weeks 4 and 8), or placebo (at baseline, Weeks 4 and 8) over a 12-week treatment period. Exploratory endpoints included the mean change from baseline in the monthly average number of days with nausea or vomiting, and days with photophobia and phonophobia during the 12-week period after the first dose of study drug. Analyses were performed in the full analysis set (all randomized patients who received ≥ 1 dose of study drug and had ≥ 10 days of post-baseline efficacy assessments on the primary endpoint) using analysis of covariance (with baseline number of days with the symptom, and years since onset of migraines as covariates) and the Wilcoxon rank-sum test.
RESULTS: Fremanezumab treatment yielded greater reductions from baseline in the monthly number of days with nausea or vomiting during the 12-week treatment period (quarterly [least-squares mean ± standard error]: –3.3±0.29 days, P=0.0009; monthly: –3.2±0.28 days, P=0.0019) compared with placebo (–2.2±0.29 days). Significant reductions in nausea or vomiting were seen as early as Week 4 (quarterly: –3.2±0.30 days, P < 0.0001; monthly: –2.9±0.29 days, P=0.0014) versus placebo (–1.9±0.29 days). Fremanezumab treatment also yielded greater reductions from baseline in the number of days with photophobia and phonophobia during the 12-week treatment period (quarterly: –3.5±0.32 days, P=0.0025; monthly: –3.7±0.32 days, P=0.0001) versus placebo (–2.4±0.32 days). Reductions in days with photophobia and phonophobia were seen as early as Week 4 (quarterly: –3.5±0.33 days, P < 0.0001; monthly: –3.5±0.32 days, P < 0.0001) versus placebo (–2.1±0.33 days).
CONCLUSIONS: Fremanezumab treatment rapidly improved non–head pain symptoms associated with migraine, including nausea or vomiting, and photophobia and phonophobia, in patients with CM.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT02638103
ETHICS APPROVAL
The study was approved by all relevant independent ethics committees or institutional review boards, according to national or local regulations.