Pegylated interferons for chronic hepatitis C virus infection: an indirect analysis of randomized trials
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.
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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
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ABSTRACT: The effectiveness and safety of amantadine (AMT) and rimantadine (RMT) for preventing and treating influenza A in adults has been systematically reviewed. However, little is known about these treatments in children and the elderly. To systematically review the effectiveness and safety of AMT and RMT in preventing and treating influenza A in children and the elderly. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2) which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1966 to June week 3, 2011) and EMBASE (1980 to June 2011). Randomised controlled trials (RCTs) or quasi-RCTs comparing AMT and/or RMT with placebo, control, other antivirals or different doses or schedules of AMT or RMT, or both, or no intervention, in children and the elderly. Two review authors independently selected trials for inclusion and assessed methodological quality. We resolved disagreements by consensus. In all comparisons except for one, we separately analysed the trials in children and the elderly using Review Manager software. A total of 12 studies involving 2494 participants (1586 children and adolescents and 908 elderly) compared AMT and RMT with placebo, paracetamol (one trial; 69 children) or zanamivir (two trials; 545 seniors). All studies were RCTs but most were still susceptible to bias. Two trials in the elderly had a high risk of bias because of incomplete outcome data. In one of those trials there was also a lack of outcome assessment blinding. Risk of bias was unclear in 10 studies due to unclear random sequence generation and allocation concealment. Only two trials in children were considered to have a low risk of bias.AMT was effective in preventing influenza A in children. A total of 773 participants were included in this outcome (risk ratio (RR) 0.11; 95% confidence interval (CI) 0.04 to 0.30). The assumed risk of influenza in the control group was 10 per 100 and the corresponding risk in the RMT group was one per 100 (95% CI 0 to 3). The quality of the evidence was considered low. For treatment purposes, RMT was beneficial for abating fever on day three of treatment. For this purpose one study was selected with low risk of bias and included 69 children (RR 0.36; 95% CI 0.14 to 0.91). The assumed risk was 38 per 100 and the corresponding risk in the RMT group was 14 per 100, 95% CI 5 to 34. The quality of the evidence was moderate.RMT did not show a prophylactic effect against influenza in the elderly, but the quality of evidence was considered very low. There were 103 participants (RR 0.45; 95% CI 0.14 to 1.41, for an assumed risk of 17 per 100 and a corresponding risk in the RMT group of 7 per 100, 95% CI 2 to 23). We did not identify any AMT trials in the elderly that met our inclusion criteria.There was no evidence of adverse effects of AMT and RMT in children or an adverse effect of RMT in the elderly. We did not identify any AMT trials in the elderly that met our inclusion criteria. AMT is effective in preventing influenza A in children but the NNTB is high (NNTB: 12 (95% CI 9 to 17). RMT probably helps the abatement of fever on day three of treatment, but the quality of the evidence is poor. Due to the small number of available studies, we could not reach a definitive conclusion on the safety of AMT or the effectiveness of RMT in preventing influenza in children and the elderly.Cochrane database of systematic reviews (Online) 01/2012; 1(11):CD002745. DOI:10.1002/14651858.CD002745.pub3 · 5.94 Impact Factor
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ABSTRACT: There has been no direct comparison of the antiviral efficacy and the adverse effects of peginterferon (PEG-IFN) alfa-2a and PEG-IFN alfa-2b when used in combination therapy with ribavirin for chronic hepatitis C virus (HCV) infection. A head-to-head comparison of the antiviral efficacy and the adverse effects of PEG-IFN alfa-2a and PEG-IFN alfa-2b was made based on the results from the IDEAL trial, a large, multicenter, prospective, randomized, controlled study performed in the United States to provide guidance for the selection of the right PEG-IFN in clinical settings. The results of the IDEAL trial were analyzed. The antiviral efficacy, as well as the adverse effects, of PEG-IFN alfa-2a and PEG-IFN alfa-2b are similar in US patients with HCV genotype 1 when used in a standard dosing regimen in combination with ribavirin.Expert Opinion on Pharmacotherapy 11/2009; 10(17):2845-57. DOI:10.1517/14656560903321521 · 3.09 Impact Factor