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

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 and Zeuzem, Stefan (2014) A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection. Journal of hepatology, 61 (6). pp. 1238-46. ISSN 1600-0641

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BACKGROUND & 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. 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 μg) or peginterferon alfa-2a (alfa; 180 μg) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48 (GT1,4) weeks. 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 μg (15/102, 15% GT1,4; 22/29, 76% GT2,3) and 240 μg (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 μg 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. CONCLUSION Lambda was associated with improved or similar rates of virologic response with fewer extrahepatic adverse events than alfa in chronic HCV infection.
Item Type: Article
Divisions: Ordensklinikum Linz Barmherzige Schwestern > Interne IV: Gastroenterologie & Hepatologie, Endokrinologie und Stoffwechsel, Ernährungsmedizin
Depositing User: Prof. Dr. Rainer Schöfl
Date Deposited: 16 Nov 2021 11:40
Last Modified: 16 Nov 2021 11:40

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