title: Safety and antiviral activity of albinterferon alfa-2b in prior interferon nonresponders with chronic hepatitis C.
abstract: OBJECTIVE
  Pegylated interferon alfa-2a/2b is used in combination with ribavirin to treat patients with chronic hepatitis C (CHC), although many do not achieve a sustained virologic response (SVR). Albinterferon alfa-2b, a recombinant protein consisting of interferon alfa-2b fused to human albumin, may increase drug exposure. This phase 2 study evaluated the safety/efficacy of albinterferon in CHC patients who had not responded to interferon-based regimens.
  
  
  METHODS
  A total of 115 patients were assigned to 5 groups given 1200 microg albinterferon every 4 weeks or 900, 1200, 1500, or 1800 microg every 2 weeks, plus oral ribavirin, for 48 weeks. The primary efficacy end point was achievement of an SVR after 24 weeks. Treatment was extended to 72 weeks for 6 slow responders who were negative for hepatitis C virus RNA after 24 weeks.
  
  
  RESULTS
  The types of adverse events were similar across groups; the overall discontinuation rate as a result of adverse events was 10.4%. Reductions in absolute neutrophil counts were less frequent in the every 4 weeks group and comparable among the every 2 weeks groups. The overall SVR rate was 17% (11% for previous nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection). An SVR occurred in 3 of 6 slow responders by 72 weeks. The greatest reductions in hepatitis C virus RNA in nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection were observed in the 1800-microg group.
  
  
  CONCLUSIONS
  In patients with CHC who did not respond to interferon-based regimens, higher doses of albinterferon had significant early antiviral activity and a low incidence of adverse events, with the types of adverse events similar to those observed with interferon.
authors.affiliation: University of Florida College of Medicine, Box 100214, Room M-440, Gainesville, Florida 32610-0214, USA. nelsodr@medicine.ufl.edu
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Vinod
authors.initials: V
authors.lastname: Rustgi
authors.forename: Vijayan
authors.initials: V
authors.lastname: Balan
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Gary L
authors.initials: GL
authors.lastname: Davis
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.forename: Louis R
authors.initials: LR
authors.lastname: Lambiase
authors.forename: Rolland C
authors.initials: RC
authors.lastname: Dickson
authors.forename: Russell H
authors.initials: RH
authors.lastname: Weisner
authors.forename: Michele
authors.initials: M
authors.lastname: Fiscella
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Cronin
authors.forename: Erik
authors.initials: E
authors.lastname: Pulkstenis
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
mesh_terms: D000328:Adult; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D000418:Albumins; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; C531108:albinterferon alfa-2b