Ritonavir-boosted danoprevir plus peginterferon alfa-2a and ribavirin in Asian chronic hepatitis C patients with or without cirrhosis
Journal
Journal of Gastroenterology and Hepatology (Australia)
Journal Volume
31
Journal Issue
10
Pages
1757-1765
Date Issued
2016
Author(s)
Tung S.-Y.
Lee Y.
Thongsawat S.
Tanwandee T.
Sheen I.-S.
Wu J.J.
Li H.
Brennan B.J.
Zhou J.
Le Pogam S.
Najera I.
Thommes J.A.
Hill G.
Abstract
Background and Aim: 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 ? 105 IU/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. ? 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd
Subjects
chronic hepatitis C; danoprevir; peginterferon alfa-2a; ribavirin; virologic response
SDGs
Other Subjects
alanine aminotransferase; danoprevir; peginterferon alpha2a; ribavirin; ritonavir; virus RNA; alpha interferon; antivirus agent; danoprevir; lactam; macrogol derivative; peginterferon alpha2a; recombinant protein; ribavirin; ritonavir; sulfonamide; adult; alanine aminotransferase blood level; alopecia; anemia; antiviral activity; Article; Asian; body mass; cellulitis; Child Pugh score; chronic hepatitis C; controlled study; coughing; decreased appetite; diarrhea; dizziness; drug bioavailability; drug efficacy; drug safety; drug withdrawal; dyspnea; EC50; elimination half-life; fatigue; female; fever; follow up; genotype; headache; human; insomnia; limit of quantitation; liquid chromatography-mass spectrometry; liver cirrhosis; major clinical study; male; maximum plasma concentration; middle aged; myalgia; nausea; neutropenia; oral clearance; phase 2 clinical trial; priority journal; pruritus; side effect; steady state; Taiwan; Thailand; thrombocytopenia; time to maximum plasma concentration; treatment duration; treatment response; ulna fracture; upper respiratory tract infection; virus resistance; volume of distribution; aged; blood; clinical trial; combination drug therapy; complication; genetics; Hepacivirus; Hepatitis C, Chronic; isolation and purification; liver cirrhosis; multicenter study; virology; young adult; Adult; Aged; Antiviral Agents; Drug Therapy, Combination; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon-alpha; Lactams; Liver Cirrhosis; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Ritonavir; RNA, Viral; Sulfonamides; Young Adult
Publisher
Blackwell Publishing
Type
journal article