Background: Pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy is the current standard of care for patients with chronic hepatitis C. Determining precisely the risk of serious adverse events (SAEs) and mortality from a single study is rather difficult because of the infrequency of such events. The aim of this systematic review was to assess the rates of SAEs and the mortality of PEG-IFN/RBV therapy in a pooled large sample, and to assess the relationship between SAEs and mortality rates and therapeutic characteristics.
Methods: A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials evaluating the efficacy and safety of PEG-IFN/RBV therapy. We calculated the crude mortality and SAE rates with 95% confidence intervals (CIs).
Results: Eighty studies with 153 treatment arms that included 27569 patients were enrolled (14401 patients treated with Peg-IFN alpha-2a/RBV and 13168 with Peg-IFN alpha-2b/RBV). All-cause and treatment-related deaths were observed in 50 (0.18%; 95% confidence interval [CI] 0.13-0.24%) and sixteen (0.058%; 95% CI 0.033-0.094%) patients, respectively. The crude SAE rate was 7.08% (95% CI 6.75-7.41%). Subgroup analysis revealed higher SAE rates in patients receiving PEG-IFN alpha-2a than in those with PEG-IFN alpha-2b (7.45 vs. 6.74%), and higher SAE rates with higher doses than with the lower doses in PEG-IFN-2a and 2b (11.94 vs. 6.99%, 7.10 vs. 5.05%, respectively), and with extended duration (> 48 weeks) than with standard duration (48 weeks) (15.5 vs. 6.67%) in PEG-IFN alpha-2a.
Conclusion: The mortality rate during PEG-IFN/RBV therapy was acceptably low, but the rate of SAEs was not negligible in a treatment for a benign disease, and the rate was affected by treatment regimens.