title: Ritonavir-boosted danoprevir plus peginterferon alfa-2a and ribavirin in Asian chronic hepatitis C patients with or without cirrhosis.
abstract: OBJECTIVE
  Chronic hepatitis C is an important public health problem in Asia. We evaluated the safety, efficacy, and pharmacokinetics of fixed-dose ritonavir-boosted danoprevir plus peginterferon alfa-2a/ribavirin in treatment-naive Asian patients with chronic hepatitis C virus (HCV) genotype (G)1 infection.
  
  
  METHODS
  Treatment-naive G1 patients in Taiwan, Thailand, and Korea with serum HCV-RNA level ≥ 105IU/mL received ritonavir-boosted danoprevir 125/100 mg twice daily plus peginterferon alfa-2a/ribavirin for either 12 (noncirrhotic patients: Arm A, n = 34) or 24 weeks (cirrhotic patients: Arm B, n = 27) in this phase II open-label study. Sustained virologic response was defined as HCV-RNA < 25 IU/mL 12 weeks after end of treatment (SVR12).
  
  
  RESULTS
  Similar SVR12 rates were achieved in Arms A (88.2%; 95% confidence interval, 73.4-95.3%) and B (88.9%; 71.9-96.2%). Most patients had G1b infection, among whom SVR12 rates in Arms A and B were 96.7% and 91.7%, respectively. The overall SVR12 rate was 94.0% in noncirrhotic Taiwanese patients (100% in the subset of G1b patients). No patients withdrew for safety reasons. Three (11%) cirrhotic patients (Arm B) experienced serious adverse events, none of which was considered to be related to treatment. No Grade 3/4 alanine aminotransferase elevations were reported. The pharmacokinetic properties of danoprevir were broadly overlapping in noncirrhotic and cirrhotic patients both on Days 1 and 14.
  
  
  CONCLUSIONS
  Ritonavir-boosted danoprevir plus peginterferon alfa-2a/ribavirin produced sustained virologic response rates > 90% after 12 weeks' treatment in noncirrhotic and 24 weeks' treatment in cirrhotic Asian patients with G1b infection and was well tolerated. These regimens are well suited to countries where G1b predominates.
authors.affiliation: Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University and Hospital, Taipei, Taiwan. kaojh@ntu.edu.tw.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.affiliation: Department of Gastroenterology, Chang Gung Memorial Hospital, Chia Yi, Taiwan.|Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shui-Yi
authors.initials: SY
authors.lastname: Tung
authors.affiliation: Pusan Paik Hospital, Inje University, Pusan, Korea.
authors.forename: Younjae
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Satawat
authors.initials: S
authors.lastname: Thongsawat
authors.affiliation: Department of Medicine, Siriraj Hospital, Bangkok, Thailand.
authors.forename: Tawesak
authors.initials: T
authors.lastname: Tanwandee
authors.affiliation: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: I-Shyan
authors.initials: IS
authors.lastname: Sheen
authors.affiliation: Ascletis BioScience, Hangzhou, China.
authors.forename: Jinzi J
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Roche Product Development, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Roche Translational and Clinical Research Center, New York, New York, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Brennan
authors.affiliation: Roche Product Development, Shanghai, China.
authors.forename: Julian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Pogam
authors.affiliation: Roche Pharma and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Isabel
authors.initials: I
authors.lastname: Najera
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Thommes
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hill
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D054833:Isoindoles; D007769:Lactams / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D047029:Lactams, Macrocyclic; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D019438:Ritonavir / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D016898:Interferon-alpha; D054833:Isoindoles; D007769:Lactams; D047029:Lactams, Macrocyclic; D012367:RNA, Viral; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; C553752:danoprevir; D011392:Proline; D019438:Ritonavir; C100416:peginterferon alfa-2a
keywords: chronic hepatitis C; danoprevir; peginterferon alfa-2a; ribavirin; virologic response