Peginterferon alfa-2a in patients with chronic hepatitis C

Background: Covalent attachment of a 40-kd branched-chain polyethylene glyc ol moiety to interferon alfa-2a results in a compound (peginterferon alfa-2 a) that has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified interferon alfa-2a. We compared the clinical effe cts of a regimen of peginterferon alfa-2a with those of a regimen of interf eron alfa-2a in the initial treatment of patients with chronic hepatitis C. Methods: We randomly assigned 531 patients with chronic hepatitis C to rece ive either 180 microg of peginterferon alfa-2a subcutaneously once per week for 48 weeks (267 patients) or 6 million units of interferon alfa-2a subcu taneously three times per week for 12 weeks, followed by 3 million units th ree times per week for 36 weeks (264 patients). All the patients were asses sed at week 72 for a sustained virologic response, defined as an undetectab le level of hepatitis C virus RNA (<100 copies per milliliter). Results: In the peginterferon group, 223 of the 267 patients completed trea tment and 206 completed follow-up. In the interferon group, 161 of the 264 patients completed treatment and 154 completed follow-up. In an intention-t o-treat analysis in which patients who missed the examination at the end of treatment or follow-up were considered not to have had a response at that point, peginterferon alfa-2a was associated with a higher rate of virologic response than was interferon alfa-2a at week 48 (69 percent vs. 28 percent , P=0.001) and at week 72 (39 percent vs. 19 percent, P=0.001). Sustained n ormalization of serum alanine aminotransferase concentrations at week 72 wa s also more common in the peginterferon group than in the interferon group (45 percent vs. 25 percent, P=0.001). The two groups were similar with resp ect to the frequency and severity of adverse events, which were typical of those associated with interferon alfa. Conclusions: In patients with chronic hepatitis C, a regimen of peginterfer on alfa-2a given once weekly is more effective than a regimen of interferon alfa-2a given three times weekly. (N Engl J Med 2000;343:1666-72.) (C) 200 0, Massachusetts Medical Society.