• Comparing the Efficacy of Direct Acting Antiviral Agents for the Treatment of Hepatitis C Virus Genotype 1

      Malone, Dan; Honkonen, Marcella; Ali, Rahma; Trinh, Sylvia; Turley, Jared; Malone, Dan; Honkonen, Marcella; College of Pharmacy, The University of Arizona (The University of Arizona., 2016)
      Objectives: To compare the efficacy of direct acting antiviral agents for the treatment of hepatitis C virus genotype 1. Our primary null hypothesis is there will be no significant difference in efficacy among the treatment regimens for hepatitis C virus, genotype 1. Methods: This meta-analysis study will use published literature identified from Embase and PubMed for phase II or III clinical trials evaluating direct acting antiviral drug regimens to treat adults with hepatitis C virus (HCV) genotype 1 infection. The primary outcome of interest is SVR at 12 weeks after treatment initiation. Data will be analyzed both descriptively as well as using Bayesian mixed treatment comparison methods. After extracting the outcome data from individual studies, the data will be analyzed using Winbugs version 1.4.3. Moreover, a random effects model and indirect/mix-treatment comparison will be used during the analysis. The random effects model accounts for both between-study and within-study variance, and is exempted from normality assumption, possessing a wider credible interval. All pair-wise odds ratios will be generated and treatment regimens will be ranked based on the likelihood of achieving SVR. Results: Overall, combinations containing sofosbuvir and ledipasvir were significantly better than all other treatments except for simeprevir (OR 0.52, 95% CI 0.28-1.00). On the other hand, daclatasvir containing regimens were non-inferior only to simeprevir (OR 0.69, 95% CI 0.35-1.31) and grazoprevir (OR 0.66, 95% CI 0.41-1.04) while being inferior to other treatments. Sofosbuvir with ledipasvir was ranked highest in terms of obtaining a sustained viral response, followed by ABT-450, grazoprevir, simeprevir, and daclatasvir respectively. In previously treated patients, sofosbuvir with ledipasvir again demonstrated the best efficacy with only grazoprevir and ABT-450 being non-inferior (OR 0.64, 95% CI 0.3368-1.212 and OR 0.73 95% CI 0.29-1.88 respectively). Sofosbuvir with ledipasvir was followed by grazoprevir, ABT-450, simeprevir, and daclatasvir containing regimens respectively. Finally, in treatment naïve patients, simeprevir containing regimens were non-inferior to all other treatment groups, including sofosbuvir regimens (OR 1.24, 95% CI 0.28-9.93). With the exception of simeprevir, sofosbuvir with ledipasvir demonstrated superiority over all treatments. Simeprevir regimens and sofosbuvir with ledipasvir regimens were followed by ABT-450. In treatment naive patients daclatasvir was found to be non-inferior to grazoprevir (OR 1.26, 95% CI 0.75-2.10). Treatment naive patients were the only group we analyzed in which daclatasvir was not the least effective regimen, with grazoprevir claiming the last position. Conclusions: Our results reject our null hypothesis that there will be no difference between different treatment regimens in HCV genotype 1 patients. Generally, the combination of sofosbuvir and ledipasvir appears to be the most effective, while daclatasvir appears to be the least.