title: Albinterferon Alfa-2b was not inferior to pegylated interferon-α in a randomized trial of patients with chronic hepatitis C virus genotype 1.
abstract: OBJECTIVE
  The current standard of care for patients with chronic hepatitis C virus (HCV) genotype 1 is once-weekly pegylated interferon-α (Peg-IFNα) plus daily ribavirin for 48 weeks. We evaluated the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of albumin and IFNα-2b.
  
  
  METHODS
  In the phase 3 ACHIEVE-1 trial, 1331 patients were assigned equally to 3 open-label, 48-week treatment groups: Peg-IFNα-2a 180 μg every week, or albIFN 900 or 1200 μg every 2 weeks administered subcutaneously, with weight-based oral ribavirin 1000-1200 mg/day. During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 μg to 900 μg because of increased pulmonary adverse events (AEs) in the 1200-μg arms of both ACHIEVE studies. Main outcome measure was sustained virologic response (SVR; undetectable serum HCV RNA at week 72).
  
  
  RESULTS
  Intention-to-treat SVR rates were 51.0% (225/441), 48.2% (213/442), and 47.3% (208/440) with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. The primary objective of showing noninferiority of albIFN 900 μg (P < .001) and 1200 μg (P = .003) vs Peg-IFNα-2a for SVR was achieved. Multivariate modeling indicated consistency of treatment effect across subgroups. Serious/severe AE rates were 23.1%, 24.0%, 28.2%; treatment discontinuation rates because of AEs were 4.1%, 10.4%, 10.0%; discontinuation rates because of respiratory AEs were 0%, 0.9%, 1.6%; with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. Hematologic abnormality rates were comparable across the Peg-IFNα-2a and albIFN 900-μg groups.
  
  
  CONCLUSIONS
  albIFN 900 μg every 2 weeks showed comparable efficacy, with similar serious/severe AE rates, although with a higher discontinuation rate, vs Peg-IFNα-2a in patients with chronic HCV genotype 1.
authors.affiliation: JW Goethe University Hospital, Frankfurt, Germany. zeuzem@em.uni-frankfurt.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lawitz
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Rustgi
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bacon
authors.forename: Mircea
authors.initials: M
authors.lastname: Grigorescu
authors.forename: Alan D
authors.initials: AD
authors.lastname: Tice
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lurie
authors.forename: Janusz
authors.initials: J
authors.lastname: Cianciara
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Cronin
authors.forename: Erik
authors.initials: E
authors.lastname: Pulkstenis
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage
chemical_list: D000418:Albumins; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C531108:albinterferon alfa-2b; C100416:peginterferon alfa-2a