Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine

JOURNAL OF HEPATOLOGY

卷:63

Article

Lalezari, Jacob¹  Sullivan, J. Greg²  Varunok, Peter³  Galen, Edward⁴  Kowdley, Kris V.⁵  Rustgi, Vinod⁶  Aguilar, Humberto⁷  McGovern, Barbara⁸  King, Martin⁸  Polepally, Akshanth R.⁸  Cohen, Daniel E.⁸ 

[1] Quest Clin Res, San Francisco, CA 94115 USA

[2] Pkway Med Ctr, Birmingham, AL USA

[3] Premier Med Grp Hudson Valley, PC, Poughkeepsie, NY USA

[4] Northwest Gastroenterol Clin, Portland, OR USA

[5] Virginia Mason Med Ctr, Inst Digest Dis, Seattle, WA 98101 USA

[6] UPMC Montefiore, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA

[7] Louisiana Res Ctr LLC, Shreveport, LA USA

[8] AbbVie Inc, N Chicago, IL USA

关键词: Hepatitis C virus;    Interferon-free therapy;    Sustained virologic response;    Opioid replacement therapy;    People who inject drugs;   

DOI  :  10.1016/j.jhep.2015.03.029

来源: Elsevier

【 摘 要 】

Background & Aims: Hepatitis C virus (HCV)-infected patients with a history of injection drug use have low rates of initiation and completion of interferon-based therapies. This study evaluated efficacy, safety, and pharmacokinetics of a 12-week all-oral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir + ribavirin in HCV genotype 1-infected patients on stable opioid replacement therapy. Methods: This was a phase II, multicenter, open-label, single-arm study in treatment-naive or peginterferon/ribavirin treatment-experienced HCV genotype 1-infected patients on methadone or buprenorphine +/- naloxone. Patients received 12 weeks of co-formulated ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) and dasabuvir (250 mg twice daily) + weight-based ribavirin. The primary efficacy endpoint was sustained virologic response 12 weeks post-treatment. Results: Thirty-eight non-cirrhotic patients on chronic methadone (n = 19) or buprenorphine (n = 19) were enrolled. A total of 37 patients (97.4%) had a sustained virologic response 12 weeks post-treatment. No patient had a viral breakthrough or relapse. One patient discontinued due to serious adverse events unrelated to study drug (cerebrovascular accident and sarcoma). The most frequent adverse events were nausea, fatigue, and headache. Eight patients had on-treatment hemoglobin concentrations < 10 g/dl. Pharmacokinetic analyses indicated no clinically meaningful impact of methadone or buprenorphine on ombitasvir, paritaprevir, ritonavir, dasabuvir, or dasabuvir M1 metabolite exposures. No dose adjustments of methadone or buprenorphine were required. Conclusions: The interferon-free regimen of ombitasvir/parita previr/ritonavir and dasabuvir + ribavirin for 12 weeks was well tolerated and achieved sustained virologic response in 97.4% of patients on opioid substitution therapy in this study. This all-oral regimen may provide an effective alternative to interferon-based therapies for HCV-infected patients with a history of injection drug use. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.

【 授权许可】

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