title: Safety of peginterferon alfa-2a plus ribavirin in a large multinational cohort of chronic hepatitis C patients.
abstract: OBJECTIVE
  Peginterferon plus ribavirin has been the standard of care for chronic hepatitis C for a decade and an essential component of combination regimens for this disease. This large multinational open-label study aimed to better define the incidence of serious adverse events (SAEs) and non-serious adverse events of special interest in patients receiving peginterferon alfa-2a/ribavirin.
  
  
  METHODS
  Patients were assigned at the investigator's discretion to 24- or 48-week treatment with peginterferon alfa-2a 180 μg/week and ribavirin 800 mg/day or 1000/1200 mg/day. All AEs, defined as SAEs and non-SAEs of special interest, were recorded during treatment and for 12 weeks thereafter. Non-SAEs of special interest included those leading to dose reduction/discontinuation, neutropenia, thrombocytopenia, anaemia, ALT elevations leading to dose modification and unknown/unexpected AEs.
  
  
  RESULTS
  Of 1675 and 7178 patients assigned to 24 and 48 weeks of treatment, respectively, 87.6 and 68.3% completed therapy, whereas 6.4 and 10.3% prematurely stopped peginterferon alfa-2a treatment because of AEs. Among patients assigned to 24 and 48 weeks, 37.4 and 46.9%, respectively, reported any AE (SAE or non-SAE of special interest); 4.2 and 6.6% reported SAEs and 35.2 and 44.0% reported non-SAEs of special interest. Female gender, increasing age and cirrhosis were significantly associated with dose reductions of either drug. Increasing age (and female gender in the case of ribavirin) was significantly associated with treatment discontinuation.
  
  
  CONCLUSIONS
  This study confirmed the safety and tolerability profile of peginterferon alfa-2a/ribavirin and identified patient subgroups at higher risk of dose reductions and discontinuations, thus allowing optimum management of AEs.
authors.affiliation: University of Calgary, Calgary, AB, Canada. samlee@ucalgary.ca
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Lee
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Roberts
authors.forename: Hanna
authors.initials: H
authors.lastname: Berak
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Dusheiko
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Harley
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
authors.forename: Petr
authors.initials: P
authors.lastname: Husa
authors.forename: Yves J
authors.initials: YJ
authors.lastname: Horsmans
authors.forename: Stephanos J
authors.initials: SJ
authors.lastname: Hadziyannis
authors.forename: E
authors.initials: E
authors.lastname: Jenny Heathcote
authors.forename: Diethelm
authors.initials: D
authors.lastname: Messinger
authors.forename: Fernando
authors.initials: F
authors.lastname: Tatsch
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
mesh_terms: D000328:Adult; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects*; D038622:Internationality; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects*; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a