Pegylated interferons for chronic hepatitis C virus infection: an indirect analysis of randomized trials.

Oregon Evidence-based Practice Center, Oregon Health & Science University, Portland, OR, USA.
Journal of Viral Hepatitis (Impact Factor: 3.08). 06/2008; 15(8):551-70. DOI: 10.1111/j.1365-2893.2008.00984.x
Source: PubMed

ABSTRACT Dual therapy with pegylated interferon and ribavirin is recommended for patients with chronic hepatitis C virus infection who meet criteria for treatment, but it is unclear whether pegylated interferon alfa-2a or pegylated interferon alfa-2b is more effective or associated with fewer adverse events. Because data from head-to-head trials of pegylated interferon regimens are sparse, we performed adjusted indirect analysis using trials comparing dual therapy with pegylated interferon alfa-2a or pegylated interferon alfa-2b vs dual therapy with non-pegylated interferon. We searched for potentially relevant randomized controlled trials using electronic databases and reference lists. A total of 16 trials met inclusion criteria. Adjusted indirect comparisons found no statistically significant differences between dual therapy with pegylated interferon alfa-2a and dual therapy with pegylated interferon alfa-2b on the outcomes sustained virologic response [relative risk (RR) = 1.59, 95% CI: 0.56-4.46], withdrawal due to adverse events (RR = 0.86, 95% CI: 0.29-2.55), anaemia (RR = 1.67, 95% CI: 0.32-8.84), depression (RR = 1.09, 95% CI: 0.41-2.90) or flu-like symptoms (RR = 1.10, 95% CI: 0.53-2.29). Adjusting for potential publication bias and stratifying analyses by indicators of methodological quality, human immunodeficiency virus infection status, hepatitis C virus genotype, dose of ribavirin or dose of pegylated interferon did not change conclusions. There is insufficient evidence to support conclusions that dual therapy with one pegylated interferon is superior to the other. However, because estimates are imprecise, our results also do not rule out a clinically significant difference. Head-to-head trials are needed to verify the results of indirect analyses and provide additional guidance on optimal treatment choices.

  • [Show abstract] [Hide abstract]
    ABSTRACT: AimTreatment of hepatitis C genotype 4 (HCV-G4) with pegylated interferon (PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta-analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin (RBV) compared to standard interferon (IFN) plus RBV. The outcome of interest is sustained virological response (SVR). Methods We searched for eligible randomized controlled trials (RCT) through May 2012. Random effects meta-analysis was used to pool the risk ratio (RR) of achieving SVR across trials. ResultsFive RCT enrolling 386 patients were included. The PEG IFN/RBV group had increased likelihood of achieving SVR (RR=1.51, 95% confidence interval [CI]=1.08-2.10). SVR was significantly higher in PEG IFN--2a compared to the --2b group (P=0.02). There was no statistically significant effect of ribavirin dosage on SVR (P=0.55). The quality of evidence was moderate overall and limited by heterogeneity. Conclusion In treatment-naive patients with HCV-G4, treatment with PEG IFN plus RBV achieves higher SVR rate than treatment with IFN plus RBV.
    Hepatology Research 02/2013; 43(12). DOI:10.1111/hepr.12084 · 2.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two types of peginterferon, alpha-2a (PEG-IFN-α2a) and 2b (PEG-IFN-α2b), are approved for the treatment of hepatitis C infection. Several high-quality studies have compared the efficacy of these two types of interferon, but it seems that any of these trials had inadequate statistical power on their own to find even a tiny difference between these two medicines. We pooled the available data in the literature to find any small difference between these two medicines. In a systematic review of the literature, randomized controlled trials comparing the use of PEG-α2a vs. 2b were assessed. The DerSimonian and Laird method was employed to run meta-analysis. The end points were virological responses. In 7 randomized controlled trials, 3518 patients were randomized to receive PEG-IFN-α2a + ribavirin (n=1762) or PEG-IFN-α2b + ribavirin (n=1756). Early virological response (EVR), early treatment response (ETR), and sustained virological response (SVR) were greater for patients treated with PEG-IFN-α2a. Odds Ratios (ORs) were 1.38 (95% confidence interval [CI] 1.11-1.71), 1.67 (95% CI 1.24-2.24), and 1.38 (95% CI 1.02-1.88) respectively. In the subset of naïve patients with genotype 1/4 and 2, ORs of SVR were 1.38 (95% CI 1.02-1.88) and 4.06 (95% CI 1.67-9.86) respectively. PEG-IFN-α2a had significantly higher rate of neutropenia OR=1.50 (95% CI 1.25-1.79) but pooled OR for withdrawal rates was not significant [OR=0.78 (95% CI 0.47-1.29)]. PEG-IFN-α2a with similar safety is more effective than PEG-IFN-α2b. A longer duration of maximum serum concentration compared with PEG-IFN-α2b (168 vs. 48-72 h.) yields a greater SVR and higher neutropenia in PEG-IFN-α2a recipients.
    Hepatitis Monthly 01/2010; 10(2):121-31. · 1.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Results of trials and meta-analyses comparing pegylated interferon (PEG-IFN)-α2a and PEG-IFN-α2b for the treatment of chronic hepatitis C are conflicting. Our objective was to determine which PEG-IFN (α2a or α2b), in association with ribavirin, is the most effective for the treatment of chronic hepatitis C by performing an updated meta-analysis. MEDLINE (1950-2012) and EMBASE (1974-2012) databases, as well as the Cochrane Central Register of controlled trials and the Cochrane Database of Systematic Reviews, were searched. Reference lists of retrieved articles were scanned, and proceedings of major international conferences were manually searched for abstracts. Randomized clinical trials and non-randomized clinical studies comparing PEG-IFN-α2a with PEG-IFN-α2b in association with ribavirin in adult patients with chronic hepatitis C were included. Studies including HIV-positive patients or liver transplant recipients were excluded. The data extraction from each study was conducted independently by two authors, with disagreements resolved by consensus or by a third reviewer. The trial quality of randomized clinical trials was assessed by taking into account generation of allocation sequence, allocation concealment, efficacy of randomization, investigator blindness, description of withdrawals and dropouts and adherence to the intention-to-treat principle. Two meta-analyses were performed, the first including randomized clinical trials only, and the second including both randomized and non-randomized clinical studies. The primary outcome measure was frequency of sustained virological response (SVR). Heterogeneity and publication bias were systematically taken into account. This meta-analysis included 26 studies, 11 randomized and 15 non-randomized, with a total of 18,260 patients: 8,125 treated with PEG-IFN-α2a and 10,135 treated with PEG-IFN-α2b. In the meta-analysis that included randomized trials only, the SVR was significantly higher for patients treated with PEG-IFN-α2a than for those treated with PEG-IFN-α2b for genotypes 1 and 4 [odds ratio (OR) 1.45; 95 % CI 1.09-2.06; p = 0.013] and for all genotypes (OR 1.34; 95 % CI 1.05-1.72; p = 0.02). In the meta-analysis including both randomized and non-randomized studies, the SVR was significantly higher for PEG-IFN-α2a than for PEG-IFN-α2b for all genotypes (OR 1.24; 95 % CI 1.10-1.40; p < 0.001) and for genotypes 1 and 4 (OR 1.25; 95 % CI 1.14-1.36; p < 0.001); for genotypes 2 and 3, the SVR was greater for treatment with PEG-IFN-α2a than with PEG-IFN-α2b, with the difference tending towards significance (OR 1.15; 95 % CI 0.98-1.35; p = 0.08). A certain degree of heterogeneity was present amongst the various studies included in this meta-analysis. Publication bias was detected (particularly for analyses including only randomized controlled trials) and taken into account using appropriate statistical methods. Current evidence suggests that PEG-IFN-α2a and ribavirin is associated with a higher SVR than PEG-IFN-α2b and ribavirin in patients mono-infected with hepatitis C, particularly for genotypes 1 and 4.
    Drugs 03/2013; 73(3):263-77. DOI:10.1007/s40265-013-0027-1 · 4.13 Impact Factor