Differences in clinical outcomes among hepatitis C genotype 1-infected patients treated with peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin: a meta-analysis

Abstract

Eric Druyts1, Edward J Mills1,2, Jean Nachega3, Christopher O'Regan4, Curtis L Cooper51Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Centre for Infectious Diseases, Stellenbosch University, Stellenbosch, South Africa; 4Division of Outcomes Research, Merck, Shire and Dohme, Hoddesdon, UK; 5Division of Infectious Diseases, University of Ottawa at The Ottawa Hospital, Ottawa, ON, CanadaBackground: With the development of new direct acting antiviral (DAA) therapy for hepatitis C, the backbone peginterferon alpha used may be of importance in maximizing treatment outcomes. To this end, the rates of sustained virologic response (SVR), relapse, and treatment discontinuation among hepatitis C genotype 1-infected patients given peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin were determined using a meta-analysis.Methods: Randomized trials examining peginterferon alpha-2a or peginterferon alpha-2b co-administered with ribavirin for 48 weeks were included. Data were extracted on SVR, relapse, and treatment discontinuations for treatment-naïve and treatment-experienced patients. Pooled proportions using fixed and random effects meta-analysis were calculated.Results: Twenty-six trials provided data on patients treated with peginterferon alpha-2a plus ribavirin, and 19 trials provided data on patients treated with peginterferon alpha-2b plus ribavirin. Five trials were direct head-to-head evaluations. In the subset of trials that included head-to-head evaluations, no significant differences were observed between the two treatments for treatment-naïve (relative risk [RR]: 1.07, 95% confidence intervals [CI]: 0.97–1.18) and treatment-experienced patients (RR: 1.27, 95% CI: 0.58–2.77). Using only active trial arms, a larger proportion of the treatment-naïve patients who were provided peginterferon alpha-2a plus ribavirin achieved a SVR (47%), which is greater than that of treatment-naïve patients who were provided peginterferon alpha-2b plus ribavirin (40% SVR achievement); however, a larger proportion of treatment-experienced patients who were provided peginterferon alpha-2b plus ribavirin achieved a SVR (16%) when compared with treatment-experienced patients given peginterferon alpha-2a plus ribavirin (12% SVR achievement). A larger proportion of relapses occurred among both treatment-naïve and treatment-experienced patients given peginterferon alpha-2a plus ribavirin, when compared with treatment-naïve and treatment-experienced patients taking peginterferon alpha-2b plus ribavirin. The proportion of patients discontinuing treatment was greater among treatment-naïve patients taking peginterferon alpha-2a plus ribavirin, but smaller among treatment-experienced patients.Conclusion: There are small differences in treatment outcomes for different types of peginterferon-alpha. Patient status and complexity of administration may differentiate clinical outcomes.Keywords: hepatitis C, genotype 1, peginterferon, ribavirin, sustained virologic response, meta-analysis