Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials

JOURNAL OF HEPATOLOGY

卷:64

Article

Dore, Gregory J.^1,2  Conway, Brian³  Luo, Yan⁴  Janczewska, Ewa⁵  Knysz, Brygida⁶  Liu, Yan⁴  Streinu-Cercel, Adrian⁷  Caruntu, Florin Alexandru⁸  Curescu, Manuela⁹  Skoien, Richard¹⁰  Ghesquiere, Wayne¹¹  Mazur, Wlodzimierz¹²  Soza, Alejandro¹³  Fuster, Francisco¹⁴  Greenbloom, Susan¹⁵  Motoc, Adriana¹⁶  Arama, Victoria⁷  Shaw, David^17,18  Tornai, Istvan¹⁹  Sasadeusz, Joseph²⁰  Dalgard, Olav²¹  Sullivan, Danielle⁴  Liu, Xuan⁴  Kapoor, Mudra⁴  Campbell, Andrew⁴  Podsadecki, Thomas⁴ 

[1] UNSW Australia, Kirby Inst, Sydney, NSW, Australia

[2] St Vincents Hosp, Sydney, NSW 2010, Australia

[3] Vancouver Infect Dis Ctr, Vancouver, BC, Canada

[4] AbbVie Inc, North Chicago, NC USA

[5] ID Clin, Myslowice, Poland

[6] Wroclaw Med Univ, Wroclaw, Poland

[7] Carol Davila Univ Med & Pharm, Natl Inst Infect Dis Prof Dr Matei Bals, Bucharest, Romania

[8] Natl Inst Infect Dis Prof Dr Matei Bals, Bucharest, Romania

[9] Univ Med & Farm Timisoara, Clin Infect Dis, Timisoara, Romania

[10] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia

[11] Isl Hlth Author, Infect Dis Sect, Victoria, BC, Canada

[12] Med Univ Silesia, Clin Dept Infect Dis, Katowice, Poland

[13] Pontificia Univ Catolica Chile, Dept Gastroenterol, Santiago, Chile

[14] Ctr Invest Cinicas Vina del Mar, Vina Del Mar, Chile

[15] Toronto Digest Dis Associates, Toronto, ON, Canada

[16] Hosp Infect Dis Dr Victor Babes, Bucharest, Romania

[17] Royal Adelaide Hosp, Dept Infect Dis, Adelaide, SA 5000, Australia

[18] Univ Adelaide, Adelaide, SA, Australia

[19] Univ Debrecen, Dept Med, Div Gastroenterol, Debrecen, Hungary

[20] Royal Melbourne Hosp, Melbourne, Vic, Australia

[21] Aker Univ Hosp, Lorenskog, Norway

关键词: Hepatitis C virus;    Telaprevir;    Interferon-free therapy;    Direct-acting antivirals;    Sustained virologic response;   

DOI  :  10.1016/j.jhep.2015.08.015

来源: Elsevier

【 摘 要 】

Background & Aims: Telaprevir plus pegylated interferon/ribavirin (TPV + PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir +/- ribavirin (OBV/PTV/r + DSV +/- RBV) and TPV + PegIFN/RBV. Methods: Treatment-naive (MALACHITE-I) or PegIFN/RBVexperienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r + DSV + weight-based RBV, OBV/PTV/r + DSV (treatment-naive, GT1b-infected patients only), or 12 weeks of TPV + PegIFN + weight-based RBV and 12-36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies. Results: Three hundred eleven treatment-naive and 148 treatment-experienced patients were randomized and dosed. Among treatment-naive patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r + DSV + RBV and TPV + PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+ DSV + RBV, OBV/PTV/r + DSV, and TPV + PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r + DSV + RBV and TPV + PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r + DSV +/- RBV than TPV + PegIFN/RBV. Rates of discontinuation due to adverse events (0-1% and 8-11%, respectively, p < 0.05) and rates of hemoglobin decline to < 10 g/dl (0-4% and 34-47%, respectively, p < 0.05) were lower for OBV/PTV/r + DSV +/- RBV than TPV + PegIFN/RBV. Conclusions: Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12 week, multi-targeted OBV/PTV/r + DSV +/- RBV regimens and 66-82% with 24-48 total weeks of TPV + PegIFN/RBV. OBV/PTV/r + DSV +/- RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

【 授权许可】

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