title: A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection.
abstract: OBJECTIVE
  Peginterferon lambda-1a (Lambda) is a type-III interferon with similar antiviral activity to alfa interferons but with a diminished extrahepatic receptor distribution, reducing the risk for extrahepatic adverse events.
  
  
  METHODS
  This was a randomized, blinded, actively-controlled, multicentre phase 2b dose-ranging study in patients chronically infected with HCV genotypes 1-4. Treatment-naive patients received Lambda (120/180/240 μg) or peginterferon alfa-2a (alfa; 180 μg) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48 (GT1,4) weeks.
  
  
  RESULTS
  Rates of undetectable HCV-RNA at week 12 (complete early virologic response [cEVR]; primary end point) were significantly higher in GT1,4 patients receiving Lambda vs. alfa (170/304, 56% vs. 38/103, 37%); with similar cEVR rates for GT2,3 (80/88, 91% vs. 26/30, 87%). Rates of undetectable HCV-RNA at week 4 were significantly higher on 180 μg (15/102, 15% GT1,4; 22/29, 76% GT2,3) and 240 μg (17/104, 16% GT1,4; 20/30, 67% GT2,3) Lambda than alfa (6/103, 6% GT1,4; 9/30, 30% GT2,3). Sustained virologic responses (post-treatment week 24) were comparable between Lambda and alfa for GT1,4 (37-46% Lambda; 37% alfa) and GT2,3 (60-76% Lambda; 53% alfa). Aminotransferase and/or bilirubin elevations were the primary dose-limiting abnormalities for Lambda; a sponsor-mandated 240 to 180 μg dose reduction was therefore implemented. Serious adverse events were comparable (3-13% Lambda; 3-7% alfa). Grade 3-4 haemoglobin, neutrophil, and platelet reductions were lower on Lambda than alfa. Among alfa patients, 28/133 (21%) had peginterferon and 31/133 (23%) had ribavirin dose reductions for haematologic abnormalities vs. 0/392 and 8/392 (2%) on Lambda. Lambda demonstrated fewer musculoskeletal (16-28% vs. 47-63%) and influenza-like events (8-23% vs. 40-46%) than alfa.
  
  
  CONCLUSIONS
  Lambda was associated with improved or similar rates of virologic response with fewer extrahepatic adverse events than alfa in chronic HCV infection.
authors: Duke Clinical Research Institute, Duke University, Durham, NC, USA.
authors: Andrew J
authors: AJ
authors: Muir
authors: University of New Mexico, Albuquerque, NM, USA.
authors: Sanjeev
authors: S
authors: Arora
authors: University of Colorado Denver & Hospital, Aurora, CO, USA.
authors: Gregory
authors: G
authors: Everson
authors: Medical University of Białystok, Białystok, Poland.
authors: Robert
authors: R
authors: Flisiak
authors: Westmead Hospital, Westmead Millennium Institute and University of Sydney, Westmead, NSW, Australia.
authors: Jacob
authors: J
authors: George
authors: Texas Clinical Research Institute, Arlington, TX, USA.
authors: Reem
authors: R
authors: Ghalib
authors: Henry Ford Hospital, Detroit, MI, USA.
authors: Stuart C
authors: SC
authors: Gordon
authors: ZymoGenetics, Bristol-Myers Squibb, Seattle, WA, USA.
authors: Todd
authors: T
authors: Gray
authors: Toronto Digestive Disease Associates, Inc., Vaughan, ON, Canada.
authors: Susan
authors: S
authors: Greenbloom
authors: SCTI Research Foundation, Coronado, CA, USA.
authors: Tarek
authors: T
authors: Hassanein
authors: ZymoGenetics, Bristol-Myers Squibb, Seattle, WA, USA.
authors: Jan
authors: J
authors: Hillson
authors: Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
authors: Maria Arantxa
authors: MA
authors: Horga
authors: Weill Cornell Medical College, New York, NY, USA.
authors: Ira M
authors: IM
authors: Jacobson
authors: Miami VA Medical Center, Miami, FL, USA.
authors: Lennox
authors: L
authors: Jeffers
authors: Virginia Mason Medical Center, Seattle, WA, USA.
authors: Kris V
authors: KV
authors: Kowdley
authors: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors: Eric
authors: E
authors: Lawitz
authors: Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors: Stefan
authors: S
authors: Lueth
authors: Fundación de Investigación, San Juan, Puerto Rico.
authors: Maribel
authors: M
authors: Rodriguez-Torres
authors: Metropolitan Research, Fairfax, VA, USA.
authors: Vinod
authors: V
authors: Rustgi
authors: ZymoGenetics, Bristol-Myers Squibb, Seattle, WA, USA.
authors: Lynn
authors: L
authors: Shemanski
authors: Liver Institute of Virginia, Newport News/Richmond, VA, USA.
authors: Mitchell L
authors: ML
authors: Shiffman
authors: Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA. Electronic address: subasree.srinivasan@bms.com.
authors: Subasree
authors: S
authors: Srinivasan
authors: Mayo Clinic in Arizona, Phoenix, AZ, USA.
authors: Hugo E
authors: HE
authors: Vargas
authors: Advanced Liver Therapies at St. Luke's Episcopal Hospital, Baylor College of Medicine, Houston, TX, USA.
authors: John M
authors: JM
authors: Vierling
authors: Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
authors: Dong
authors: D
authors: Xu
authors: Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
authors: Juan C
authors: JC
authors: Lopez-Talavera
authors: Department of Medicine, JW Goethe University Hospital, Frankfurt, Germany.
authors: Stefan
authors: S
authors: Zeuzem
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D007378:Interleukins / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000600496:peginterferon lambda-1a; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
keywords: Efficacy; SVR; Safety; Treatment-naive; Type III interferon