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

被引：124

作者：

Muir, Andrew J. ^{[1
]}

Arora, Sanjeev ^{[2
]}

Everson, Gregory ^{[3
]}

Flisiak, Robert ^{[4
]}

George, Jacob ^{[5
,6
]}

Ghalib, Reem ^{[7
]}

Gordon, Stuart C. ^{[8
]}

Gray, Todd ^{[9
]}

Greenbloom, Susan ^{[10
]}

Hassanein, Tarek ^{[11
]}

Hillson, Jan ^{[9
]}

Horga, Maria Arantxa ^{[12
]}

Jacobson, Ira M. ^{[13
]}

Jeffers, Lennox ^{[14
]}

Kowdley, Kris V. ^{[15
]}

Lawitz, Eric ^{[16
]}

Lueth, Stefan ^{[17
]}

Rodriguez-Torres, Maribel ^{[18
]}

Rustgi, Vinod ^{[9
,19
]}

Shemanski, Lynn ^{[9
]}

Shiffman, Mitchell L. ^{[20
]}

Srinivasan, Subasree ^{[12
]}

Vargas, Hugo E. ^{[21
]}

Vierling, John M. ^{[22
]}

Xu, Dong ^{[12
]}

Lopez-Talavera, Juan C. ^{[12
]}

Zeuzem, Stefan ^{[23
]}

机构：

[1] Duke Univ, Duke Clin Res Inst, Durham, NC USA

[2] Univ New Mexico, Albuquerque, NM 87131 USA

[3] Univ Colorado Denver & Hosp, Aurora, CO USA

[4] Med Univ Bialystok, Bialystok, Poland

[5] Westmead Hosp, Westmead Millennium Inst, Westmead, NSW 2145, Australia

[6] Univ Sydney, Westmead, NSW 2145, Australia

[7] Texas Clin Res Inst, Arlington, TX USA

[8] Henry Ford Hosp, Detroit, MI 48202 USA

[9] Bristol Myers Squibb Co, ZymoGenetics, Seattle, WA USA

[10] Toronto Digest Dis Associates Inc, Vaughan, ON, Canada

[11] SCTI Res Fdn, Coronado, CA USA

[12] Bristol Myers Squibb Co, Res & Dev, Wallingford, CT 06492 USA

[13] Weill Cornell Med Coll, New York, NY USA

[14] Miami VA Med Ctr, Miami, FL USA

[15] Virginia Mason Med Ctr, Seattle, WA 98101 USA

[16] Univ Texas Hlth Sci Ctr San Antonio, Texas Liver Inst, San Antonio, TX 78229 USA

[17] Univ Klinikum Hamburg Eppendorf, Hamburg, Germany

[18] Fdn Invest, San Juan, PR USA

[19] Metropolitan Res, Fairfax, VA USA

[20] Liver Inst Virginia, Richmond, VA USA

[21] Mayo Clin Arizona, Phoenix, AZ USA

[22] St Lukes Episcopal Hosp, Baylor Coll Med, Houston, TX 77030 USA

[23] JW Goethe Univ Hosp, Dept Med, Frankfurt, Germany

来源：

JOURNAL OF HEPATOLOGY | 2014年 / 61卷 / 06期

关键词：

Type III interferon; SVR; Safety; Efficacy; Treatment-naive; CHRONIC HEPATITIS-C; IFN-LAMBDA; RIBAVIRIN THERAPY; INTERFERON-ALPHA; BOCEPREVIR; TELAPREVIR; GENOTYPE-2; MANAGEMENT; ANEMIA; IL28B;

D O I：

10.1016/j.jhep.2014.07.022

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 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. 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. Conclusion: Lambda was associated with improved or similar rates of virologic response with fewer extrahepatic adverse events than alfa in chronic HCV infection. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：1238 / 1246

页数：9

共 43 条

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