title: A model-based meta-analysis of sofosbuvir-based treatments in chronic hepatitis C patients.
abstract: The objective of this study was to compare the efficacy of sofosbuvir-based treatments in patients with chronic hepatitis C virus (HCV) infection using a model-based meta-analysis (MBMA). A bibliographic search was performed to identify clinical trials involving sofosbuvir as a unique direct-acting antiviral (DAA) agent or together with daclatasvir, ledipasvir or simeprevir for the treatment of diagnosed HCV infection. The time course of the virological response (VR) was modelled to estimate the effect of treatment and the influence of population characteristics on the longitudinal efficacy profile. The model was validated and simulations of 10 different treatment schedules were performed. Data from 19 clinical trials were included in the analysis. According to the developed model, therapy with sofosbuvir+ledipasvir is the most effective therapy in all scenarios, but it does not differ greatly in terms of sustained VR with respect to other combinations of DAA treatments. In conclusion, this MBMA generates knowledge regarding hypothetical head-to-head trials that have not been conducted previously. Therapies with sofosbuvir+ledipasvir are probably the most effective sofosbuvir-based treatments.
authors.affiliation: Pharmacy Department, University Clinical Hospital of Valencia, Avda. Blasco Ibañez 17, Valencia 46010, Spain; Pharmacy and Pharmaceutical Technology Department, University of Valencia, Valencia, Spain. Electronic address: alejandroperezpitarch@gmail.com.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pérez-Pitarch
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, University of Valencia, Valencia, Spain; Pharmacy Department, Doctor Peset University Hospital, Valencia, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Guglieri-López
authors.affiliation: Pharmacy Department, University Clinical Hospital of Valencia, Avda. Blasco Ibañez 17, Valencia 46010, Spain; Pharmacy and Pharmaceutical Technology Department, University of Valencia, Valencia, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ferriols-Lisart
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, University of Valencia, Valencia, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Merino-Sanjuán
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008962:Models, Theoretical; D011759:Pyrrolidines; D000069616:Simeprevir / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D005449:Fluorenes; D007093:Imidazoles; D011759:Pyrrolidines; C586541:ledipasvir; D000069616:Simeprevir; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: Hepatitis C virus; Meta-analysis; Modelling; Simulation; Sofosbuvir