title: ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection.
abstract: OBJECTIVE
  The interferon-free regimen of ABT-450 (a protease inhibitor), ritonavir, ombitasvir (an NS5A inhibitor), dasabuvir (a non-nucleoside polymerase inhibitor), and ribavirin has shown efficacy in patients with hepatitis C virus (HCV) genotype 1b infection-the most prevalent subgenotype worldwide. We evaluated whether ribavirin is necessary for ABT-450, ritonavir, ombitasvir, and dasabuvir to produce high rates of sustained virologic response (SVR) in these patients.
  
  
  METHODS
  We performed a multicenter, open-label, phase 3 trial of 179 patients with HCV genotype 1b infection, without cirrhosis, previously treated with peginterferon and ribavirin. Patients were assigned randomly (1:1) to groups given ABT-450, ritonavir, ombitasvir, and dasabuvir, with ribavirin (group 1) or without (group 2) for 12 weeks. The primary end point was SVR 12 weeks after treatment (SVR12). We assessed the noninferiority of this regimen to the rate of response reported (64%) for a similar population treated with telaprevir, peginterferon, and ribavirin.
  
  
  RESULTS
  Groups 1 and 2 each had high rates of SVR12, which were noninferior to the reported rate of response to the combination of telaprevir, peginterferon, and ribavirin (group 1: 96.6%; 95% confidence interval, 92.8%-100%; and group 2: 100%; 95% confidence interval, 95.9%-100%). The rate of response in group 2 was noninferior to that of group 1. No virologic failure occurred during the study. Two patients (1.1%) discontinued the study owing to adverse events, both in group 1. The most common adverse events in groups 1 and 2 were fatigue (31.9% vs 15.8%) and headache (24.2% vs 23.2%), respectively. Decreases in hemoglobin level to less than the lower limit of normal were more frequent in group 1 (42.0% vs 5.5% in group 2; P < .001), although only 2 patients had hemoglobin levels less than 10 g/dL.
  
  
  CONCLUSIONS
  The interferon-free regimen of ABT-450, ritonavir, ombitasvir, and dasabuvir, with or without ribavirin, produces a high rate of SVR12 in treatment-experienced patients with HCV genotype 1b infection. Both regimens are well tolerated, as shown by the low rate of discontinuations and generally mild adverse events. ClinicalTrials.gov number: NCT01674725.
authors.affiliation: University of Bologna, Bologna, Italy. Electronic address: pietro.andreone@unibo.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.affiliation: Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Massimo G
authors.initials: MG
authors.lastname: Colombo
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Enejosa
authors.affiliation: Karadeniz Technical University, Trabzon, Turkey.
authors.forename: Iftihar
authors.initials: I
authors.lastname: Koksal
authors.affiliation: Medical University of Vienna, Internal Medicine III, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Elisabeth Hospital, Linz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maieron
authors.affiliation: University Hospital, Zurich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.affiliation: Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Horsmans
authors.affiliation: Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Weiland
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Henk W
authors.initials: HW
authors.lastname: Reesink
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Lino
authors.initials: L
authors.lastname: Rodrigues
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Yiran B
authors.initials: YB
authors.lastname: Hu
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Thomas
authors.initials: T
authors.lastname: Podsadecki
authors.affiliation: AbbVie, Inc, North Chicago, Illinois.
authors.forename: Barry
authors.initials: B
authors.lastname: Bernstein
mesh_terms: D015081:2-Naphthylamine; D000328:Adult; D000368:Aged; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D011647:Puerto Rico; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014633:Valine; D019562:Viral Load
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D015415:Biomarkers; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D012367:RNA, Viral; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir
keywords: IFN; Interferon-Free Therapy; PEARL-II; Ribavirin-Free