Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study

被引：84

作者：

Hezode, Christophe ^{[1
]}

Hirschfield, Gideon M. ^{[2
,3
]}

Ghesquiere, Wayne ^{[4
,5
]}

Sievert, William ^{[6
,7
]}

Rodriguez-Torres, Maribel ^{[8
]}

Shafran, Stephen D. ^{[9
]}

Thuluvath, Paul J. ^{[10
]}

Tatum, Harvey A. ^{[11
]}

Waked, Imam ^{[12
]}

Esmat, Gamal ^{[13
]}

Lawitz, Eric J. ^{[14
]}

Rustgi, Vinod K. ^{[15
]}

Pol, Stanislas ^{[16
,17
]}

Weis, Nina ^{[18
]}

Pockros, Paul J. ^{[19
]}

Bourliere, Marc ^{[20
]}

Serfaty, Lawrence ^{[21
]}

Vierling, John M. ^{[22
]}

Fried, Michael W. ^{[23
]}

Weiland, Ola ^{[24
]}

Brunetto, Maurizia R. ^{[25
]}

Everson, Gregory T. ^{[26
]}

Zeuzem, Stefan ^{[27
]}

Kwo, Paul Y. ^{[28
]}

Sulkowski, Mark ^{[29
]}

Braeu, Norbert ^{[30
]}

Hernandez, Dennis ^{[31
]}

McPhee, Fiona ^{[31
]}

Wind-Rotolo, Megan ^{[32
]}

Liu, Zhaohui ^{[33
]}

Noviello, Stephanie ^{[32
]}

Hughes, Eric A. ^{[32
]}

Yin, Philip D. ^{[31
]}

Schnittman, Steven ^{[31
]}

机构：

[1] Univ Paris Est, Hop Henri Mondor, AP HP, INSERM,U955, Creteil, France

[2] Univ Birmingham, Ctr Liver Res, Birmingham, W Midlands, England

[3] Univ Birmingham, NIHR Biomed Res Unit, Birmingham, W Midlands, England

[4] Vancouver Isl Hlth Author, Victoria, BC, Canada

[5] Univ British Columbia, Victoria, BC, Canada

[6] Monash Univ, Melbourne, Vic 3004, Australia

[7] Monash Hlth, Melbourne, Vic, Australia

[8] San Juan Bautista Sch Med, Fdn Invest, San Juan, PR USA

[9] Univ Alberta Hosp, Edmonton, AB T6G 2B7, Canada

[10] Mercy Med Ctr, Baltimore, MD USA

[11] Opt Hlth Res LLC, Tulsa, OK USA

[12] Natl Liver Inst, Shibin Al Kawm, Egypt

[13] Cairo Univ, Fac Med, Endem Med & Hepatogastroenterol Dept, Cairo, Egypt

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

[15] Metropolitan Res, Fairfax, VA USA

[16] Univ Paris 05, Hop Cochin, INSERM, U1016, Paris, France

[17] Univ Paris 05, Hop Cochin, Liver Unit, Paris, France

[18] Copenhagen Univ Hosp, Hvidovre, Denmark

[19] Scripps Clin, La Jolla, CA 92037 USA

[20] Hop St Joseph, Marseille, France

[21] Hop St Antoine, F-75571 Paris, France

[22] Baylor Coll Med, Houston, TX 77030 USA

[23] Univ N Carolina, Chapel Hill, NC USA

[24] Karolinska Inst, Karolinska Univ Hosp Huddinge, Stockholm, Sweden

[25] Univ Hosp Pisa, Hepatol Unit, Pisa, Italy

[26] Univ Colorado Denver, Aurora, CO USA

[27] Goethe Univ Frankfurt, D-60054 Frankfurt, Germany

[28] Indiana Univ, Indianapolis, IN 46204 USA

[29] Johns Hopkins Univ, Baltimore, MD USA

[30] James J Peters VA Med Ctr, Bronx, NY USA

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

[32] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ USA

[33] Bristol Myers Squibb Res & Dev, Hopewell, NJ USA

来源：

GUT | 2015年 / 64卷 / 06期

关键词：

SIMEPREVIR TMC435; NS5A INHIBITOR; VIRUS EPIDEMIOLOGY; BMS-790052; SOFOSBUVIR; BURDEN; ANEMIA;

D O I：

10.1136/gutjnl-2014-307498

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objective To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. Design In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20mg or 60mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA<lower limit of quantitation at Week 4 and undetectable at Week 10) were rerandomised at Week 12 to continue daclatasvir/peginterferon-alfa-2a/ribavirin for 24weeks total duration or to placebo/peginterferon-alfa-2a/ribavirin for another 12weeks. Patients without PDR and placebo patients continued peginterferon-alfa/ribavirin through Week 48. Primary efficacy endpoints were undetectable HCV-RNA at Weeks 4 and 12 (extended rapid virologic response, eRVR) and at 24weeks post-treatment (sustained virologic response, SVR24) among genotype 1-infected patients. Results Overall, eRVR was achieved by 54.4% (80/147) of genotype 1-infected patients receiving daclatasvir 20mg, 54.1% (79/146) receiving 60mg versus 13.9% (10/72) receiving placebo. SVR24 was achieved among 87 (59.2%), 87 (59.6%), and 27 (37.5%) patients in these groups, respectively. Higher proportions of genotype 4-infected patients receiving daclatasvir 20mg (66.7%; 8/12) or 60mg (100.0%; 12/12) achieved SVR24 versus placebo (50.0%; 3/6). A majority of daclatasvir-treated patients achieved PDR and experienced less virologic failure and higher SVR24 rates with a shortened 24-week treatment duration. Adverse events occurred with similar frequency across all treatment groups. Conclusions The combination of daclatasvir/peginterferon-alfa/ribavirin was generally well tolerated and achieved higher SVR24 rates compared with placebo/peginterferon-alfa/ribavirin among patients infected with HCV genotype 1 or 4. Trial registration number NCT01125189.

引用

页码：948 / 956

页数：9

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