title: Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis.
abstract: OBJECTIVE
  Interferon-free treatment options are rapidly evolving for patients with chronic hepatitis C virus (HCV) genotype 1b (GT1b) infection with cirrhosis and for nonresponders to prior pegylated interferon and ribavirin therapy. We performed a phase 2b, open-label trial of the combination of ombitasvir (a NS5A replication complex inhibitor), paritaprevir, and ritonavir (an NS3/4A protease inhibitor)-an interferon- and ribavirin-free regimen-in difficult-to-treat patients, including prior null responders and patients with cirrhosis.
  
  
  METHODS
  In an international study, 82 patients without cirrhosis (42 treatment-naive and 40 prior null responders) and 99 with cirrhosis (47 treatment-naive and 52 treatment-experienced with prior relapse or a null or partial response) with chronic HCV GT1b infection received ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily for 12 weeks (without cirrhosis) or 24 weeks (with cirrhosis). The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12).
  
  
  RESULTS
  In treatment-naive and null responder patients without cirrhosis, rates of SVR12 were 95.2% and 90.0%, respectively. In treatment-naive and treatment-experienced patients with cirrhosis, rates of SVR12 were 97.9% and 96.2%, respectively. No clinically meaningful differences in rates of SVR12 were observed between patients with or without cirrhosis. Virologic relapse occurred in 3 null responders without cirrhosis and 1 with cirrhosis; virologic breakthrough occurred in 1 null responder without cirrhosis. Common adverse events included headache, asthenia, pruritus, and diarrhea. One patient discontinued taking the drugs because of treatment-related adverse events.
  
  
  CONCLUSIONS
  An interferon- and ribavirin-free regimen of ombitasvir, paritaprevir, and ritonavir, achieved high rates of SVR12 in patients with HCV GT1b infection with and without cirrhosis. This regimen was well tolerated and was associated with low rates of treatment discontinuation. ClinicalTrials.gov no: NCT01685203.
authors.affiliation: Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.affiliation: Outpatient Clinic, Saint Laszlo Hospital, Budapest, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Makara
authors.affiliation: Ege University, Faculty of Medicine, Department of Gastroenterology, Izmir, Turkey.
authors.forename: Ulus Salih
authors.initials: US
authors.lastname: Akarca
authors.affiliation: Mercy Medical Center and University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thuluvath
authors.affiliation: National Institute of Infectious Diseases Prof. Dr. Matei Balş, Bucharest, Romania.
authors.forename: Liliana Lucia
authors.initials: LL
authors.lastname: Preotescu
authors.affiliation: Premier Medical Group, New York Medical College, Poughkeepsie, New York.
authors.forename: Peter
authors.initials: P
authors.lastname: Varunok
authors.affiliation: Liver Section and CIBERehd, Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Rosa Ma
authors.initials: RM
authors.lastname: Morillas
authors.affiliation: Infectious Diseases Clinical Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Coleen
authors.initials: C
authors.lastname: Hall
authors.affiliation: Infectious Diseases Clinical Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Mobashery
authors.affiliation: Infectious Diseases Clinical Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Redman
authors.affiliation: Infectious Diseases Clinical Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Tami
authors.initials: T
authors.lastname: Pilot-Matias
authors.affiliation: Infectious Diseases Clinical Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Regis A
authors.initials: RA
authors.lastname: Vilchez
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France. Electronic address: christophe.hezode@hmn.aphp.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D047029:Lactams, Macrocyclic; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D047028:Macrocyclic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D012008:Recurrence; D012074:Remission Induction; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014633:Valine; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D002352:Carrier Proteins; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D011392:Proline; D019438:Ritonavir; D013449:Sulfonamides; D014633:Valine; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C586094:ombitasvir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C585405:paritaprevir
keywords: Direct-Acting Antivirals; HCV Genotype 1b; Interferon-Free/Ribavirin-Free