title: Safety profile of standard- vs. high-dose peginterferon alfa-2a plus standard-dose ribavirin in HCV genotype 1/4 patients: pooled analysis from 5 randomized studies.
abstract: OBJECTIVE
  This analysis examines the safety profile of standard- versus high-dose peginterferon alfa-2a.
  
  
  METHODS
  Data were pooled from five trials including HCV genotype 1- or 4-infected naive and treatment-experienced patients (n = 2,940). Patients were randomized to receive peginterferon alfa-2a at 180 μg/week (standard-dose; n = 1,672) or 360 μg/week (high-dose; n = 1,268) plus ribavirin 1,000/1,200 mg/day for 12 weeks; after 12 weeks, all received standard dose. This safety analysis was restricted to the first 12 weeks.
  
  
  RESULTS
  In standard and high-dose groups, similar frequencies of serious adverse events (SAEs, 3.2 and 4.2%, respectively) and treatment discontinuations for safety reasons (2.8 and 2.9%) were reported. More patients reported weight decrease as an adverse event (AE) in the 360 μg/week group (7.7 vs. 3.3%). Significant (p < 0.05) independent predictors for discontinuation due to safety were older age, male gender, lower albumin and low neutrophil count, but not the starting dose of peginterferon alfa-2a. Although more laboratory abnormalities were reported in patients receiving high-dose peginterferon alfa-2a, this was not reflected in AEs or discontinuations, suggesting these are adequately managed by dose modification.
  
  
  CONCLUSIONS
  High-dose peginterferon alfa-2a for 12 weeks does not significantly increase the incidence of SAEs or discontinuations for safety reasons, beyond that of a standard dose regimen.
authors.affiliation: Hôpital Beaujon, 100 Boulevard Du General Leclerc, Clichy, 92110, France. patrick.marcellin@bjn.aphp.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Roberts
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Harrison
authors.forename: Donald M
authors.initials: DM
authors.lastname: Jensen
authors.forename: Stephanos
authors.initials: S
authors.lastname: Hadziyannis
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.forename: Martin
authors.initials: M
authors.lastname: Weltman
authors.forename: Diethelm
authors.initials: D
authors.lastname: Messinger
authors.forename: Fernando
authors.initials: F
authors.lastname: Tatsch
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
mesh_terms: D000367:Age Factors; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a