title: Network meta-analysis of first- and second-generation protease inhibitors for chronic hepatitis C genotype 1: efficacy based on RVR and SVR 24.
abstract: OBJECTIVE
  This study aimed to compare the efficacy among direct-acting antiviral agents (first and second-generation direct-acting antiviral agents (DAAs)) with placebo and with standard dual therapy (pegylated interferon + ribavirin (Peg-IFN + RBV)) in terms of rapid virologic response (RVR) and sustained virologic response (SVR) in chronic hepatitis C genotype 1 treatment.
  
  
  METHODS
  We performed a systematic review of randomized controlled trials (RCTs) in MEDLINE, International Pharmaceutical Abstracts, Cochrane Library, SCIELO, and Scopus and conducted a network meta-analysis to compare the efficacy of boceprevir (BOC), daclatasvir (DCV), grazoprevir, simeprevir (SMV) and telaprevir (TVR), in treatment-naive and treatment-experienced patients.
  
  
  RESULTS
  Sixteen studies encompassing 7171 patients were analysed. Associations between DAAs therapies (IFN-free 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 Peg-IFN + 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. Node-splitting analysis showed that our networks are robust (p > 0.05).
  
  
  CONCLUSIONS
  The superiority of DAAs over placebo or standard dual therapy with Peg-IFN + RBV was confirmed, indicating the greater efficacy of DCV. This study is the first network meta-analysis 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 outcomes.
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Campus III, Av. Pref. Lothário Meissner, 632, Jardim Botânico, Curitiba, PR, 80210-170, Brazil.
authors.forename: Helena H
authors.initials: HH
authors.lastname: Borba
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Campus III, Av. Pref. Lothário Meissner, 632, Jardim Botânico, Curitiba, PR, 80210-170, Brazil.
authors.forename: Astrid
authors.initials: A
authors.lastname: Wiens
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Campus III, Av. Pref. Lothário Meissner, 632, Jardim Botânico, Curitiba, PR, 80210-170, Brazil.
authors.forename: Laiza M
authors.initials: LM
authors.lastname: Steimbach
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Campus III, Av. Pref. Lothário Meissner, 632, Jardim Botânico, Curitiba, PR, 80210-170, Brazil.
authors.forename: Cassio M
authors.initials: CM
authors.lastname: Perlin
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Campus III, Av. Pref. Lothário Meissner, 632, Jardim Botânico, Curitiba, PR, 80210-170, Brazil.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Tonin
authors.affiliation: Gastroenterology Service, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Maria L A
authors.initials: ML
authors.lastname: Pedroso
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Department of Social Pharmacy, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernandez-Llimos
authors.affiliation: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Campus III, Av. Pref. Lothário Meissner, 632, Jardim Botânico, Curitiba, PR, 80210-170, Brazil. pontarolo@ufpr.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pontarolo
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012254:Ribavirin / Q000627:therapeutic use; D000072230:Sustained Virologic Response
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons
keywords: Direct-acting antivirals; Hepatitis C; Network meta-analysis; Systematic review