Which is the IDEAL Peginterferon for Hepatitis C: A Meta-Analysis of both Pegylated Interferons in the Treatment of HCV-Infected Patients

C infections with the hepatitis C virus (HCV) represent a major global health problem, with around 170 million patients at risk of developing life-threatening complications such as liver cirrhosis or hepatocellular carcinoma. The standard treatment of care is a combination of weekly pegylated interferon (peginterferon) alfa and daily ribavirin for 24-72 weeks, dependent on HCV genotype and the patient’s individual virological response to therapy (1, 2). Currently, there are two forms of peginterferon licensed for the treatment of hepatitis C: peginterferon alfa-2a (Pegasys, Roche) and peginterferon alfa-2b (Pegintron, Schering-Plough). Although direct pharmacodynamic comparisons of both substances have shown that they differ considerably with respect to pharmocokinetics and initial virological suppression (3), it remained largely unclear whether this is relevant for clinical endpoints, especially for achieving sustained virological response in HCV-infected patients. In fact, the largest phase-3 trials for peginterferon alfa-2a and alfa-2b initially yielded somewhat similar outcomes (4, 5), establishing a “gut feeling” among many hepatologists worldwide that both substances were very likely equally potent in clinical practice. This was strongly supported by the largest endpoint trial to directly compare these two peginterferons, the IDEAL trial. In this trial, more than 3,000 patients were randomized to receive either peginterferon alfa-2b (at two different doses, i.e. 1.0 or 1.5 μg/kg per week) or alfa-2a (at 180 μg/week), and similar sustained virological response (SVR) rates were reported for all three treatment groups (6). Two smaller recent studies reported by Rumi and Ascione this year (7, 8) challenged this conclusion by revealing a modest but significant increase in SVR for patients treated with peginterferon alfa-2a (Table 1). However, findings from single trials, especially when yielding contradictory results, are rarely definitive. It is therefore important to conduct a metaanalysis of the available high-quality studies. Prof. Alavian and colleagues present in this issue of Hepatitis Monthly a thorough, up-to-date, and extensive metaanalysis of studies comparing the efficacy of the two peginterferons in patients chronically infected by HCV (9). This meta-analysis included 3,518 patients