title: The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation.
abstract: BACKGROUND
  Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events.
  
  
  OBJECTIVE
  To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease.
  
  
  METHODS
  Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way.
  
  
  RESULTS
  The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation.
  
  
  CONCLUSIONS
  We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Zonneveld
authors.forename: H J
authors.initials: HJ
authors.lastname: Flink
authors.forename: E
authors.initials: E
authors.lastname: Verhey
authors.forename: H
authors.initials: H
authors.lastname: Senturk
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.forename: U S
authors.initials: US
authors.lastname: Akarca
authors.forename: Y
authors.initials: Y
authors.lastname: Cakaloglu
authors.forename: C
authors.initials: C
authors.lastname: Simon
authors.forename: T M K
authors.initials: TM
authors.lastname: So
authors.forename: G
authors.initials: G
authors.lastname: Gerken
authors.forename: R A
authors.initials: RA
authors.lastname: de Man
authors.forename: B E
authors.initials: BE
authors.lastname: Hansen
authors.forename: S W
authors.initials: SW
authors.lastname: Schalm
authors.forename: H L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001424:Bacterial Infections / Q000150:complications; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b