Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b.
The study objective was to compare the efficacy and safety of peginterferon lambda-1a combined with ribavirin/daclatasvir (Lambda/RBV/DCV), versus peginterferon alfa-2a combined with ribavirin/telaprevir (Alfa/RBV/TVR), in patients chronically infected with hepatitis C virus (HCV), genotype 1b. This was a prospective, randomized, open-label, phase 3 study (NCT01718158) in adults (aged ≥18 years) who were treatment naïve or prior relapsers to peginterferon alfa/ribavirin therapy. The primary endpoint was sustained virologic response at post-treatment follow-up week 12 (SVR12). Patients were randomized in a 2:1 ratio to receive 24 weeks of Lambda/RBV/DCV or response-guided 24 or 48 weeks of Alfa/RBV/TVR. Overall, 440 patients were treated (294 with Lambda/RBV/DCV; 146 with Alfa/RBV/TVR). The proportion of patients achieving SVR12 was 88.8% in the Lambda/RBV/DCV arm and 70.5% in the Alfa/RBV/TVR arm (difference between arms: 18.3%; 95% confidence interval: 9.9-25.7; P < 0.0001). Patients in the Lambda/RBV/DCV group had fewer rash-related adverse events (AEs), cytopenic abnormalities, flu-like symptoms, serious AEs, and discontinuations due to AEs, but more liver abnormalities than those in the Alfa/RBV/TVR group. In conclusion, treatment with Lambda/RBV/DCV led to higher SVR12 rates and a more favorable safety profile than Alfa/RBV/TVR in patients with chronic HCV, genotype 1b infection.
1 Department of Infectious Diseases and Hepatology, Medical University of Bialystok , Bialystok, Poland .
Robert
R
Flisiak
2 Department of Hepatobiliary and Pancreatology, Saga Prefectural Hospital Koseikan , Saga, Japan .
Seiji
S
Kawazoe
3 Moscow State University of Medicine and Dentistry , Moscow, Russia .
Olga
O
Znoyko
4 Department of Liver, Ziv Medical Center and Bar-Ilan University , Safed, Israel .
Nimer
N
Assy
5 Liver Unit, Hospital Italiano de Buenos Aires , Buenos Aires, Argentina .
Adrian
A
Gadano
6 Hepatitis Research Center, National Taiwan University , Taipei, Taiwan .
Jia-Horng
JH
Kao
7 Gastroenterology, Yonsei University College of Medicine , Seoul, South Korea .
Kwan-Sik
KS
Lee
8 Research and Development, Bristol-Myers Squibb, Inc. , Wallingford, Connecticut.
Ricardo
R
Zwirtes
8 Research and Development, Bristol-Myers Squibb, Inc. , Wallingford, Connecticut.
Simon
S
Portsmouth
9 Research and Development, Bristol-Myers Squibb, Inc. , Princeton, New Jersey.
Yuping
Y
Dong
8 Research and Development, Bristol-Myers Squibb, Inc. , Wallingford, Connecticut.
Dong
D
Xu
10 Department of Hepatology, Toranomon Hospital , Tokyo, Japan .
Hiromitsu
H
Kumada
8 Research and Development, Bristol-Myers Squibb, Inc. , Wallingford, Connecticut.
Subasree
S
Srinivasan
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002219:Carbamates; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011759:Pyrrolidines; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D016898:Interferon-alpha; D009842:Oligopeptides; D011759:Pyrrolidines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; D014633:Valine; C549273:daclatasvir; C100416:peginterferon alfa-2a
clinical trial; daclatasvir; hepatitis C; interferon lambda-1a; ribavirin