A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection

作者：Muir Andrew J; Arora Sanjeev; Everson Gregory; Flisiak Robert; George Jacob; Ghalib Reem; Gordon Stuart C; Gray Todd; Greenbloom Susan; Hassanein Tarek; Hillson Jan; Horga Maria Arantxa; Jacobson Ira M; Jeffers Lennox; Kowdley Kris V; Lawitz Eric; Lueth Stefan; Rodriguez Torres Maribel; Rustgi Vinod; Shemanski Lynn; Shiffman Mitchell L; Srinivasan Subasree^*; Vargas Hugo E; Vierling John M; Xu Dong; Lopez Talavera Juan C; Zeuzem Stefan

来源：Journal of Hepatology, 2014, 61(6): 1238-1246.

DOI：10.1016/j.jhep.2014.07.022

• Type III interferon
• SVR
• Safety
• Efficacy
• Treatment-naive

Background %26 Aims: Peginterferon lambda-1a (Lambda) is a type-III interferon with similar antiviral activity to alfa interferons but with a diminished extrahepatic receptor distribution, reducing the risk for extrahepatic adverse events. %26lt;br%26gt;Methods: This was a randomized, blinded, actively-controlled, multicentre phase 2b dose-ranging study in patients chronically infected with HCV genotypes 1-4. Treatment-naive patients received Lambda (120/180/240 mu g) or peginterferon alfa-2a (alfa; 180 mu g) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48 (GT1,4) weeks. %26lt;br%26gt;Results: Rates of undetectable HCV-RNA at week 12 (complete early virologic response [cEVR]; primary end point) were significantly higher in GT1,4 patients receiving Lambda vs. alfa (170/304, 56% vs. 38/103, 37%); with similar cEVR rates for GT2,3 (80/88, 91% vs. 26/30, 87%). Rates of undetectable HCV-RNA at week 4 were significantly higher on 180 mu g (15/102, 15% GT1,4; 22/29, 76% GT2,3) and 240 mu g (17/104, 16% GT1,4; 20/30, 67% GT2,3) Lambda than alfa (6/103, 6% GT1,4; 9/30, 30% GT2,3). Sustained virologic responses (post-treatment week 24) were comparable between Lambda and alfa for GT1,4 (37-46% Lambda; 37% alfa) and GT2,3 (60-76% Lambda; 53% alfa). Aminotransferase and/or bilirubin elevations were the primary dose-limiting abnormalities for Lambda; a sponsor-mandated 240 to 180 mu g dose reduction was therefore implemented. Serious adverse events were comparable (3-13% Lambda; 3-7% alfa). Grade 3-4 haemoglobin, neutrophil, and platelet reductions were lower on Lambda than alfa. Among alfa patients, 28/133 (21%) had peginterferon and 31/133 (23%) had ribavirin dose reductions for haematologic abnormalities vs. 0/392 and 8/392 (2%) on Lambda. Lambda demonstrated fewer musculoskeletal (16-28% vs. 47-63%) and influenza-like events (8-23% vs. 40-46%) than alfa. %26lt;br%26gt;Conclusion: Lambda was associated with improved or similar rates of virologic response with fewer extrahepatic adverse events than alfa in chronic HCV infection.

• 出版日期2014-12