title: Ledipasvir/sofosbuvir with or without ribavirin for the treatment of chronic hepatitis C genotype 1: A pairwise meta-analysis.
abstract: OBJECTIVE
  Ledipasvir with sofosbuvir (LED/SOF) for the treatment of patients infected with genotype 1 hepatitis C virus can be used with or without ribavirin (RBV). RBV is well known to promote significant adverse events (AE). The aim of this study was to compare the efficacy and safety of treatment with LED/SOF, with or without RBV, in patients infected with hepatitis C virus genotype 1.
  
  
  METHODS
  We performed a systematic review followed by a pairwise meta-analysis including randomized controlled trials that reported efficacy (rapid virological response, sustained virological response at 4 and 12 weeks post-treatment (SVR4 and 12), and viral relapse) and safety outcomes (any AE, serious AE, discontinuation owing to AE, anemia, and rash). It was performed a subgroup analysis evaluating the SVR12 including only cirrhotic patients. Results were reported as risk ratios (RR) and with 95% confidence intervals (95% CI).
  
  
  RESULTS
  Seven randomized controlled trials were analyzed. LED/SOF with RBV showed a worse safety profile when compared with LED/SOF without RBV for the following outcomes: any AE (RR 0.56 [95% CI 0.46-0.69]), anemia (RR 0.08 [95% CI 0.04-0.17]), and rash (RR 0.35 [95% CI 0.19-0.65]). No significant differences were observed regarding serious AE, rapid virological response, SVR4, SVR12, or viral relapse. The subgroup analysis did not show significant differences between either treatment groups.
  
  
  CONCLUSIONS
  Administration of LED/SOF + RBV to treatment-naïve patients with or without cirrhosis, and non-cirrhotic treatment-experienced patients, did not promote significant additional benefits. Furthermore, it is still unclear whether cirrhotic treatment-experienced patients could benefit from combined therapy.
authors: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Vinicius L
authors: VL
authors: Ferreira
authors: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Nayara A
authors: NA
authors: Assis Jarek
authors: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Fernanda S
authors: FS
authors: Tonin
authors: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Helena H L
authors: HH
authors: Borba
authors: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Astrid
authors: A
authors: Wiens
authors: Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Dominique A
authors: DA
authors: Muzzillo
authors: Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Roberto
authors: R
authors: Pontarolo
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D016206:Databases, Bibliographic; D004359:Drug Therapy, Combination; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: hepatitis C; meta-analysis; systematic review; treatment