Efficacy and safety of boceprevir plus peginterferon-ribavirin in patients with HCV G1 infection and advanced fibrosis/cirrhosis

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• 作者：Savino Bruno¹ ; ^{savino.bruno@fbf.milano.it} ; John M. Vierling² ; Rafael Esteban³ ; Lisa M. Nyberg⁴ ; Hugo Tanno⁵ ; Zachary Goodman⁶ ; Fred Poordad⁷ ; ^&dagger ; ; Bruce Bacon⁸ ; Keith Gottesdiener⁹ ; Lisa D. Pedicone⁹ ; ^&Dagger ; ; Janice K. Albrecht⁹ ; Clifford A. Brass⁹ ; ^§ ; ; Seth Thompson⁹ ; Margaret H. Burroughs⁹
• 关键词：BOC ; boceprevir ; PR ; peginterferon&ndash ; ribavirin ; HCV-G1 ; hepatitis C virus ; genotype-1 ; RGT ; response guided therapy ; SVR ; sustained virologic response ; HCC ; hepatocellular carcinoma ; NS3/4A ; non-specific protein 3/4a.
• 刊名：Journal of Hepatology
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：58
• 期：3
• 页码：479-487
• 全文大小：860 K

文摘

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Background & Aims

We assessed the safety and efficacy of boceprevir (BOC) plus peginterferon-ribavirin (PR) in patients with HCV-G1 infection and advanced fibrosis/cirrhosis (Metavir F3/F4).

Methods

In two randomized controlled studies of previously untreated and previous treatment failures, patients received a 4-week lead-in of PR followed by PR plus placebo for 44 weeks (PR48); PR plus BOC using response guided therapy (BOC/RGT); or PR plus BOC for 44 weeks (BOC/PR48).

Results

The trials enrolled 178 patients with F3/4. HCV RNA levels at week 4 and 8 were highly predictive of response. No patient with F3/4 in the PR48 arm with a <1 log₁₀ decline in HCV RNA at week 4 achieved SVR, whereas those randomized to BOC/RGT or BOC/PR48 had SVR rates of 11-33 % (F3) and 10-14 % (F4). In these latter groups, patients with high baseline viral load (>2 ¡Á 10⁶ IU/ml) had an overall SVR rate of 6 % (2/33). For patients with a ?1 log₁₀ decline at week 4, SVR rates in the BOC/PR48 arm of SPRINT-2 and RESPOND-2, respectively, were 77 % and 87 % vs. 18 % and 50 % for PR48; SVR rates in early responders (undetectable HCV RNA at week 8) were 90-93 % in the BOC/PR48 arm. Neutropenia and thrombocytopenia were more common in cirrhotics than non-cirrhotics.

Conclusions

BOC improves SVR rates in patients with F3/4, and longer treatment duration provides the most benefit. With triple therapy, SVR rates are modest in F4 patients with a <1 log₁₀ decline at week 4, thus the 4-week PR lead-in aids in the assessment of early futility.