title: Response-guided telaprevir combination treatment for hepatitis C virus infection.
abstract: BACKGROUND
  Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations.
  
  
  METHODS
  We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 μg per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48.
  
  
  RESULTS
  Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001).
  
  
  CONCLUSIONS
  In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.).
authors.affiliation: Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0595, USA. shermake@ucmail.uc.edu
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Steven L
authors.initials: SL
authors.lastname: Flamm
authors.forename: Nezam H
authors.initials: NH
authors.lastname: Afdhal
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fried
authors.forename: Michael
authors.initials: M
authors.lastname: Adler
authors.forename: Hendrik W
authors.initials: HW
authors.lastname: Reesink
authors.forename: Marie
authors.initials: M
authors.lastname: Martin
authors.forename: Abdul J
authors.initials: AJ
authors.lastname: Sankoh
authors.forename: Nathalie
authors.initials: N
authors.lastname: Adda
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kauffman
authors.forename: Shelley
authors.initials: S
authors.lastname: George
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Wright
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a