title: ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV.
abstract: BACKGROUND
  The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.
  
  
  METHODS
  We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment.
  
  
  RESULTS
  The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea.
  
  
  CONCLUSIONS
  Twelve weeks of treatment with ABT-450/r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection. (Funded by AbbVie; PEARL-III and PEARL-IV ClinicalTrials.gov numbers, NCT01767116 and NCT01833533.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: David
authors.initials: D
authors.lastname: Bernstein
authors.forename: Jacob
authors.initials: J
authors.lastname: Lalezari
authors.forename: Daniel
authors.initials: D
authors.lastname: Cohen
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Edward
authors.initials: E
authors.lastname: Tam
authors.forename: Rui T
authors.initials: RT
authors.lastname: Marinho
authors.forename: Naoky
authors.initials: N
authors.lastname: Tsai
authors.forename: Anders
authors.initials: A
authors.lastname: Nyberg
authors.forename: Terry D
authors.initials: TD
authors.lastname: Box
authors.forename: Ziad
authors.initials: Z
authors.lastname: Younes
authors.forename: Pedram
authors.initials: P
authors.lastname: Enayati
authors.forename: Sinikka
authors.initials: S
authors.lastname: Green
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Baruch
authors.forename: Bal Raj
authors.initials: BR
authors.lastname: Bhandari
authors.forename: Florin Alexandru
authors.initials: FA
authors.lastname: Caruntu
authors.forename: Thomas
authors.initials: T
authors.lastname: Sepe
authors.forename: Vladimir
authors.initials: V
authors.lastname: Chulanov
authors.forename: Ewa
authors.initials: E
authors.lastname: Janczewska
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.forename: Judit
authors.initials: J
authors.lastname: Gervain
authors.forename: Ramon
authors.initials: R
authors.lastname: Planas
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.forename: Tarek
authors.initials: T
authors.lastname: Hassanein
authors.forename: Wangang
authors.initials: W
authors.lastname: Xie
authors.forename: Martin
authors.initials: M
authors.lastname: King
authors.forename: Thomas
authors.initials: T
authors.lastname: Podsadecki
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
mesh_terms: D000328:Adult; D000368:Aged; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000032:analysis; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D014633:Valine
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D006454:Hemoglobins; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D012367:RNA, Viral; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D011392:Proline; D014633:Valine; C585405:paritaprevir