title: A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C.
abstract: BACKGROUND
  A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection.
  
  
  METHODS
  Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR.
  
  
  RESULTS
  A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm.
  
  
  CONCLUSIONS
  In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary-related events, and more Lambda patients were lost to follow-up.
authors.affiliation: Department of Infectious Diseases and Hepatology, Medical University of Bialystock, Bialystock, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.affiliation: Bon Secours Liver Institute of Virginia, Richmond, Virginia, United States of America.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Shiffman
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Donostia, San Sebastián, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Arenas
authors.affiliation: Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.affiliation: Department of Higher Level General Medicine, Russian State Medical University, Moscow, Russia.
authors.forename: Igor
authors.initials: I
authors.lastname: Nikitin
authors.affiliation: Research and Development, Bristol-Myers Squibb, Inc., Wallingford, Connecticut, United States of America.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Research and Development, Bristol-Myers Squibb, Inc., Wallingford, Connecticut, United States of America.
authors.forename: Khurram
authors.initials: K
authors.lastname: Rana
authors.affiliation: Research and Development, Bristol-Myers Squibb, Inc., Wallingford, Connecticut, United States of America.
authors.forename: Subasree
authors.initials: S
authors.lastname: Srinivasan
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006402:Hematologic Diseases / Q000209:etiology; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C000600496:peginterferon lambda-1a; C486464:telaprevir; C100416:peginterferon alfa-2a