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J Hepatol. 2016 Jan;64(1):19-28. doi: 10.1016/j.jhep.2015.08.015. Epub 2015 Aug 29.

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

Author information

1
Kirby Institute, UNSW Australia, and St. Vincent's Hospital, Sydney, Australia. Electronic address: gdore@kirby.unsw.edu.au.
2
Vancouver Infectious Diseases Centre, Vancouver, Canada.
3
AbbVie Inc., North Chicago, USA.
4
ID Clinic, Mysłowice, Poland.
5
Wroclaw Medical University, Wroclaw, Poland.
6
Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases "Prof. Dr. Matei Balș", Bucharest, Romania.
7
National Institute for Infectious Diseases "Prof. Dr. Matei Bals", Bucharest, Romania.
8
Clinic of Infectious Diseases, University of Medicine and Pharmacy Timisoara, Timisoara, Romania.
9
Royal Brisbane and Women's Hospital, Brisbane, Australia.
10
Island Health Authority, Section of Infectious Diseases, Victoria, Canada.
11
Clinical Department of Infectious Disease, Medical University of Silesia, Katowice, Poland.
12
Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile.
13
Centro de Investigaciones Cínicas Viña del Mar, Viña del Mar, Chile.
14
Toronto Digestive Disease Associates, Toronto, Canada.
15
Hospital of Infectious Diseases Dr. Victor Babes, Bucharest, Romania.
16
Royal Adelaide Hospital, Infectious Diseases Department, and University of Adelaide, Adelaide, Australia.
17
University of Debrecen, Department of Medicine, Division of Gastroenterology, Debrecen, Hungary.
18
Royal Melbourne Hospital, Melbourne, Victoria, Australia.
19
Akershus University Hospital, Lorenskog, Norway.

Abstract

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-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r+DSV+weight-based RBV, OBV/PTV/r+DSV (treatment-naïve, GT1b-infected patients only), or 12weeks of TPV+PegIFN+weight-based RBV and 12-36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies.

RESULTS:

Three hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve 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 <10g/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 12week, 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.

KEYWORDS:

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

PMID:
26321288
DOI:
10.1016/j.jhep.2015.08.015
[Indexed for MEDLINE]
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