Boceprevir for chronic HCV genotype 1 infection in patients with prior treatment failure to peginterferon/ribavirin, including prior null response

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• 作者：John M. Vierling¹ ; ^{vierling@bcm.tmc.edu" class="auth_mail} ; Mitchell Davis² ; Steven Flamm³ ; Stuart C. Gordon⁴ ; Eric Lawitz⁵ ; Eric M. Yoshida⁶ ; Joseph Galati⁷ ; Velimir Luketic⁸ ; Jonathan McCone⁹ ; Ira Jacobson¹⁰ ; Patrick Marcellin¹¹ ; Andrew J. Muir¹² ; Fred Poordad⁵ ; Lisa D. Pedicone¹³ ; ^&dagger ; ; Janice Albrecht¹³ ; ^&dagger ; ; Clifford Brass¹³ ; ^&dagger ; ; Anita Y.M. Howe¹³ ; Lynn Y. Colvard¹³ ; Frans A. Helmond¹³ ; Weiping Deng¹³ ; Michelle Treitel¹³ ; ^&dagger ; ; Janice Wahl¹³ ; Jean-Pierre Bronowicki¹⁴
• 关键词：HCV ; hepatitis C virus ; BOC ; boceprevir ; PR ; peginterferon with ribavirin ; SVR ; sustained virological response ; TW ; treatment week ; NS3/4A ; nonstructural proteins 3 and 4A ; IU/ml ; international units per milliliter ; mITT ; modified intent-to-treat ; ITT ; intent-to-treat ; FW ; follow-up week ; MedDRA ; Medical Dictionary for Regulatory Activities ; WHO ; World Health Organization ; FDA ; Food and Drug Administration ; RAV ; resistance associated variant
• 刊名：Journal of Hepatology
• 出版年：April, 2014
• 年：2014
• 卷：60
• 期：4
• 页码：748-756
• 全文大小：839 K

文摘

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Background & Aims

Boceprevir with peginterferon/ribavirin (BOC/PR) leads to significantly higher sustained virological response (SVR) rates in patients with chronic hepatitis C and partial response or relapse after prior treatment with peginterferon/ribavirin. We studied the efficacy of BOC/PR in patients with prior treatment failure, including those with a null response (<2-log₁₀ decline in HCV RNA), to peginterferon/ribavirin.

Methods

Patients in the control arms of boceprevir Phase 2/3 studies who did not achieve SVR were re-treated with BOC/PR for up to 44 weeks. Patients enrolling >2 weeks after end-of-treatment in the prior study received PR for 4 weeks before adding boceprevir.

Results

Of 168 patients enrolled, four discontinued from the PR lead-in and 164 received BOC/PR. Baseline viral load was >800,000 IU/ml in 77% of patients; 62% had HCV genotype 1a, and 10% were cirrhotic. In the ITT analysis (all 168 patients), SVR was achieved in 20 (38%) of 52 patients with prior null response, 57 (67%) of 85 with prior partial response, and 27 (93%) of 29 with prior relapse. In the mITT analysis (164 BOC/PR-treated patients), SVR rates were 41% (20/49), 67% (57/85), and 96% (27/28), respectively. SVR was achieved by 48% of patients with <1-log₁₀ decline in HCV-RNA after lead-in and 76% of those with 猢?-log₁₀ decline or undetectable HCV-RNA after lead-in. The most common adverse events were anemia (49%), fatigue (48%), and dysgeusia (35%); 8% of patients discontinued due to adverse events.

Conclusions

Re-treatment with BOC/PR improved SVR rates in all patient subgroups, including those with prior null response.