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

被引：58

作者：

Dore, Gregory J. ^{[1
,2
]}

Conway, Brian ^{[3
]}

Luo, Yan ^{[4
]}

Janczewska, Ewa ^{[5
]}

Knysz, Brygida ^{[6
]}

Liu, Yan ^{[4
]}

Streinu-Cercel, Adrian ^{[7
]}

Caruntu, Florin Alexandru ^{[8
]}

Curescu, Manuela ^{[9
]}

Skoien, Richard ^{[10
]}

Ghesquiere, Wayne ^{[11
]}

Mazur, Wlodzimierz ^{[12
]}

Soza, Alejandro ^{[13
]}

Fuster, Francisco ^{[14
]}

Greenbloom, Susan ^{[15
]}

Motoc, Adriana ^{[16
]}

Arama, Victoria ^{[7
]}

Shaw, David ^{[17
,18
]}

Tornai, Istvan ^{[19
]}

Sasadeusz, Joseph ^{[20
]}

Dalgard, Olav ^{[21
]}

Sullivan, Danielle ^{[4
]}

Liu, Xuan ^{[4
]}

Kapoor, Mudra ^{[4
]}

Campbell, Andrew ^{[4
]}

Podsadecki, Thomas ^{[4
]}

机构：

[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

来源：

JOURNAL OF HEPATOLOGY | 2016年 / 64卷 / 01期

关键词：

Hepatitis C virus; Telaprevir; Interferon-free therapy; Direct-acting antivirals; Sustained virologic response; CHRONIC HEPATITIS-C; TREATMENT-NAIVE PATIENTS; QUALITY-OF-LIFE; PEGYLATED INTERFERON; REPORTED OUTCOMES; PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2B; TELAPREVIR; SOFOSBUVIR; ABT-450/R-OMBITASVIR;

D O I：

10.1016/j.jhep.2015.08.015

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

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.

引用

页码：19 / 28

页数：10

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