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Title of Journal: Eur J Clin Pharmacol

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Abbravation: European Journal of Clinical Pharmacology

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Springer Berlin Heidelberg

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DOI

10.1007/bf02519915

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1432-1041

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Network metaanalysis of first and secondgenerat

Authors: Helena H Borba Astrid Wiens Laiza M Steimbach Cassio M Perlin Fernanda S Tonin Maria L A Pedroso Fernando FernandezLlimos Roberto Pontarolo
Publish Date: 2016/10/19
Volume: 73, Issue: 1, Pages: 1-14
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Abstract

This study aimed to compare the efficacy among directacting antiviral agents first and secondgeneration directacting antiviral agents DAAs with placebo and with standard dual therapy pegylated interferon + ribavirin PegIFN + RBV in terms of rapid virologic response RVR and sustained virologic response SVR in chronic hepatitis C genotype 1 treatmentWe performed a systematic review of randomized controlled trials RCTs in MEDLINE International Pharmaceutical Abstracts Cochrane Library SCIELO and Scopus and conducted a network metaanalysis to compare the efficacy of boceprevir BOC daclatasvir DCV grazoprevir simeprevir SMV and telaprevir TVR in treatmentnaive and treatmentexperienced patientsSixteen studies encompassing 7171 patients were analysed Associations between DAAs therapies IFNfree regimens could not be addressed since no common comparator was found in the RCTs among these associations and the other agents included in the present analysis All agents were more efficacious than placebo or PegIFN + RBV in terms of RVR while only BOC and SMV showed statistically significant superiority for the SVR outcome when compared to placebo or standard dual therapy No significant differences between the DAAs were observed The analysis prioritized treatment with DCV for both efficacy outcomes Nodesplitting analysis showed that our networks are robust p  005The superiority of DAAs over placebo or standard dual therapy with PegIFN + RBV was confirmed indicating the greater efficacy of DCV This study is the first network metaanalysis that included RVR as an outcome in the evaluation of these agents via indirect comparison Further investigation should be carried out addressing safety and tolerability outcomesAll coauthors listed contributed to the final manuscript in the following manner RP conceived the study RP AW FFL and HHB participated in its design HHB CMP and LMS participated in the systematic review and data extraction FST assisted HHB in the statistical analysis for Bayesian metaanalysis FFL assisted HHB in the manuscript preparation including analysis of results MLAP provided a clinical view on the subject and assistance for additional analyses All authors provided revisions and approved the final manuscript submitted

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