title: Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials.
abstract: OBJECTIVE
  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.
authors: Kirby Institute, UNSW Australia, and St. Vincent's Hospital, Sydney, Australia. Electronic address: gdore@kirby.unsw.edu.au.
authors: Gregory J
authors: GJ
authors: Dore
authors: Vancouver Infectious Diseases Centre, Vancouver, Canada.
authors: Brian
authors: B
authors: Conway
authors: AbbVie Inc., North Chicago, USA.
authors: Yan
authors: Y
authors: Luo
authors: ID Clinic, Mysłowice, Poland.
authors: Ewa
authors: E
authors: Janczewska
authors: Wroclaw Medical University, Wroclaw, Poland.
authors: Brygida
authors: B
authors: Knysz
authors: AbbVie Inc., North Chicago, USA.
authors: Yan
authors: Y
authors: Liu
authors: Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases "Prof. Dr. Matei Balș", Bucharest, Romania.
authors: Adrian
authors: A
authors: Streinu-Cercel
authors: National Institute for Infectious Diseases "Prof. Dr. Matei Bals", Bucharest, Romania.
authors: Florin Alexandru
authors: FA
authors: Caruntu
authors: Clinic of Infectious Diseases, University of Medicine and Pharmacy Timisoara, Timisoara, Romania.
authors: Manuela
authors: M
authors: Curescu
authors: Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors: Richard
authors: R
authors: Skoien
authors: Island Health Authority, Section of Infectious Diseases, Victoria, Canada.
authors: Wayne
authors: W
authors: Ghesquiere
authors: Clinical Department of Infectious Disease, Medical University of Silesia, Katowice, Poland.
authors: Włodzimierz
authors: W
authors: Mazur
authors: Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Alejandro
authors: A
authors: Soza
authors: Centro de Investigaciones Cínicas Viña del Mar, Viña del Mar, Chile.
authors: Francisco
authors: F
authors: Fuster
authors: Toronto Digestive Disease Associates, Toronto, Canada.
authors: Susan
authors: S
authors: Greenbloom
authors: Hospital of Infectious Diseases Dr. Victor Babes, Bucharest, Romania.
authors: Adriana
authors: A
authors: Motoc
authors: Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases "Prof. Dr. Matei Balș", Bucharest, Romania.
authors: Victoria
authors: V
authors: Arama
authors: Royal Adelaide Hospital, Infectious Diseases Department, and University of Adelaide, Adelaide, Australia.
authors: David
authors: D
authors: Shaw
authors: University of Debrecen, Department of Medicine, Division of Gastroenterology, Debrecen, Hungary.
authors: Istvan
authors: I
authors: Tornai
authors: Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors: Joseph
authors: J
authors: Sasadeusz
authors: Akershus University Hospital, Lorenskog, Norway.
authors: Olav
authors: O
authors: Dalgard
authors: AbbVie Inc., North Chicago, USA.
authors: Danielle
authors: D
authors: Sullivan
authors: AbbVie Inc., North Chicago, USA.
authors: Xuan
authors: X
authors: Liu
authors: AbbVie Inc., North Chicago, USA.
authors: Mudra
authors: M
authors: Kapoor
authors: AbbVie Inc., North Chicago, USA.
authors: Andrew
authors: A
authors: Campbell
authors: AbbVie Inc., North Chicago, USA.
authors: Thomas
authors: T
authors: Podsadecki
mesh_terms: D015081:2-Naphthylamine; D000328:Adult; D000368:Aged; D000813:Anilides / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011392:Proline / Q000031:analogs & derivatives; D011994:Recombinant Proteins / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014633:Valine
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D011994:Recombinant Proteins; D013449:Sulfonamides; C586094:ombitasvir; D011092:Polyethylene Glycols; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; C417083:peginterferon alfa-2b; D014633:Valine; C585405:paritaprevir
keywords: Direct-acting antivirals; Hepatitis C virus; Interferon-free therapy; Sustained virologic response; Telaprevir