Boceprevir Plus Peginterferon Alfa-2a/Ribavirin in Treatment-Naïve Hepatitis C Virus Genotype 1 Patients: International Phase IIIb/IV TriCo Trial

被引：2
作者：
Ferenci P. [1 ]
Caruntu F.A. [2 ]
Lengyel G. [3 ]
Messinger D. [4 ]
Bakalos G. [5 ]
Flisiak R. [6 ]
机构：
[1] Department of Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna, Vienna
[2] National Institute for Infectious Diseases ‘Matei Bals’, Bucharest
[3] 2nd Department of Medicine, Semmelweis University, Budapest
[4] PROMETRIS GmbH, Mannheim
[5] F. Hoffmann-La Roche Ltd, Basel
[6] Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok
来源：
Infectious Diseases and Therapy | 2016年 / 5卷 / 2期
关键词：
Boceprevir; Chronic hepatitis C; Peginterferon alfa-2a; Ribavirin; Sustained virological response;
D O I：
10.1007/s40121-016-0110-5
中图分类号：
学科分类号：
摘要：
Introduction: Boceprevir was not previously studied with peginterferon alfa-2a/ribavirin in phase III trials in treatment-naïve chronic hepatitis C patients. The international phase IIIb/IV TriCo study was, therefore, designed to evaluate boceprevir in combination with peginterferon alfa-2a/ribavirin in treatment-naïve genotype 1 patients. Methods: A total of 165 treatment-naïve genotype 1 patients were assigned to boceprevir plus peginterferon alfa-2a/ribavirin therapy according to the label. All patients received a 4-week lead-in with peginterferon alfa-2a/ribavirin, after which boceprevir (2400 mg/day) was introduced. The total duration of treatment ranged from 28 to 48 weeks depending on the virological response at Weeks 4, 8, and 24, and on fibrosis status. The primary efficacy outcome was sustained virological response (SVR) [undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) 12 weeks after actual end of treatment, SVR12]. Results: The overall SVR12 rate was 81% (133/165, 95% confidence interval 74–86%). After 8 weeks of treatment, 61% of patients had undetectable HCV RNA, and 78 patients (47%) had an early response (undetectable HCV RNA at Weeks 8 and 24) and were eligible to stop all therapy at Week 28. Among early responders the SVR12 rate was 95% (74/78), and among patients with cirrhosis assigned to 48 weeks’ treatment, the SVR12 rate was 67% (14/21). The overall relapse rate was 7% (10/143), and was 4% (3/77) among early responders. The most common adverse events were anemia (41%), neutropenia (32%), and dysgeusia (31%). Conclusion: High SVR12 rates can be achieved with boceprevir plus peginterferon alfa-2a/ribavirin in treatment-naïve HCV genotype 1 patients, including patients with well-compensated cirrhosis. Treatment is well tolerated when label restrictions are taken into account. Trial Registration Number: ClinicalTrials.gov Identifier: NCT01591460. Funding: F. Hoffmann-La Roche Ltd. © 2016, The Author(s).
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页码：113 / 124
页数：11
相关论文
共 16 条
  • [1] Recommendations for testing, managing, and treating hepatitis C, American Association for the Study of Liver Diseases and Infectious Diseases Society of America
  • [2] Afdhal N., Zeuzem S., Kwo P., Chojkier M., Gitlin N., Puoti M., Et al., Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection, N Engl J Med, 370, 20, pp. 1889-1898, (2014)
  • [3] Afdhal N., Reddy K.R., Nelson D.R., Lawitz E., Gordon S.C., Schiff E., Et al., Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection, N Engl J Med, 370, 16, pp. 1483-1493, (2014)
  • [4] J Hepatol, 2015, 63, pp. 199-236, (2015)
  • [5] Ferenci P., Bernstein D., Lalezari J., Cohen D., Luo Y., Cooper C., Et al., ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV, N Engl J Med, 370, 21, pp. 1983-1992, (2014)
  • [6] Kowdley K.V., Gordon S.C., Reddy K.R., Rossaro L., Bernstein D.E., Lawitz E., Et al., Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis, N Engl J Med, 370, 20, pp. 1879-1888, (2014)
  • [7] Lawitz E., Sulkowski M.S., Ghalib R., Rodriguez-Torres M., Younossi Z.M., Corregidor A., Et al., Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study, Lancet, 384, 9956, pp. 1756-1765, (2014)
  • [8] Ferenci P., Reddy K.R., Impact of HCV protease-inhibitor-based triple therapy for chronic HCV genotype 1 infection, Antivir Ther, 16, 8, pp. 1187-1201, (2011)
  • [9] Poordad F., McCone J., Bacon B.R., Bruno S., Manns M.P., Sulkowski M.S., Et al., Boceprevir for untreated chronic HCV genotype 1 infection, N Engl J Med, 364, 13, pp. 1195-1206, (2011)
  • [10] Mishra P., Murray J., Birnkrant D., Direct-acting antiviral drug approvals for treatment of chronic hepatitis C virus infection: scientific and regulatory approaches to clinical trial designs, Hepatology, 62, 4, pp. 1298-1303, (2015)
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