Calcitonin Gene-Related Peptide Receptor Antagonists (Gepants) for the Acute Treatment of Nausea in Episodic Migraine: A Systematic Review and Meta-Analysis. Headache Chan, T. L., Cowan, R. P., Woldeamanuel, Y. W. 2020


OBJECTIVE: To synthesize the evidence on the efficacy of calcitonin gene-related peptide receptor antagonists (gepants) from all clinical trials addressing nausea treatment for episodic migraine.INTRODUCTION: Nausea is one of the most bothersome symptoms in patients with migraine. The most bothersome symptom is part of the outcomes explored in clinical trials.METHODS: Published clinical trials for this project were identified via searches of 4 bibliographic databases: PubMed (includes MEDLINE), Embase, Web of Science, and the Cochrane Library. Individual search strategies included terms related to calcitonin gene-related peptide, nausea, and vomiting. Random-effects meta-analysis was conducted to estimate the overall efficacy of gepants for nausea treatment. Heterogeneity, publication bias, small-study bias, and potential confounders were explored using Galbraith plot, sensitivity analysis, meta-regression, and Egger's regression tests. Cumulative meta-analysis was done to detect temporal trend from accumulating trials.RESULTS: The meta-analysis involved 23,008 participants in 65 clinical trials from 14 published articles; 10,770 subjects participated in gepant treatment arms while 12,238 subjects participated in placebo or non-gepant arms (85% females, mean age 41years in both arms). Nearly all studies used a 2-hour incidence of nausea as an outcome measure. An overall combined effect size with an odds ratio of 1.29 (95% CI 1.18, 1.40, P=.001; I2 =42.8%) showed the efficacy of gepants for the treatment of nausea in episodic migraine. Galbraith plot demonstrated that 98.4% of studies were within 2 standard deviations from the regression line, indicating lack of significant heterogeneity and outliers. Meta-analysis results were robust to sensitivity analysis, small-study bias, and publication bias (Kendall's Tau -0.09, P=.29; Egger's regression P=.67). Meta-regression showed that both age and sex ratio were not confounding the meta-analysis (omnibus P=.69). Cumulative meta-analysis indicated that the effect size remained stable for studies conducted after 2011, with accumulating evidence continuing to favor efficacy of gepants for the treatment of nausea in episodic migraine.CONCLUSION: There is sufficient evidence to support the efficacy of gepants for the treatment of nausea in episodic migraine. Future research may focus on examining this efficacy in under-represented patient populations (males, older age groups) and in chronic migraine.

View details for DOI 10.1111/head.13858

View details for PubMedID 32515018