title: Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data.
abstract: OBJECTIVE
  Retreatment with a combination of alpha interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies.
  
  
  METHODS
  To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000-1200 mg/daily depending on body weight) was given for 24-60 (mean 39.5) weeks.
  
  
  RESULTS
  Biochemical end of treatment and sustained responses were observed in 271/581 (46.6%; 95% confidence interval (CI) 42.6-50.7%) and in 109/581 (18.7%; 95% CI 15.6-22.0%) cases, respectively. Two hundred and six of 532 patients (38.7%; 95% CI 34.6-42.9%) had an end of treatment complete response to retreatment while a complete sustained response occurred in 88 of 559 (15.7%; 95% CI 12.8-18.8%). Fifty four of 581 patients (9.2%; 95% CI 7.0-11.7%) stopped retreatment due to adverse effects. By logistic regression, complete sustained response was predicted independently by age <45 years (p=0.04), by normal pretreatment gamma-glutamyltransferase levels (p=0.01), and by a second course total IFN dose of at least 432 mega units (p=0.008).
  
  
  CONCLUSIONS
  The overall low probability of effectiveness argues against indiscriminate retreatment of all IFN monotherapy non-responders with IFN/ribavirin. Patients less than 45 years old with normal gamma-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%.
authors.affiliation: Istituto Metodologie Diagnostiche Avanzate, Consiglio Nazionale delle Ricerche, and Cattedra e Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy. camma@ismeda.pa.cnr.it
authors.forename: C
authors.initials: C
authors.lastname: Cammà
authors.forename: S
authors.initials: S
authors.lastname: Bruno
authors.forename: F
authors.initials: F
authors.lastname: Schepis
authors.forename: O
authors.initials: O
authors.lastname: Lo Iacono
authors.forename: P
authors.initials: P
authors.lastname: Andreone
authors.forename: A G
authors.initials: AG
authors.lastname: Gramenzi
authors.forename: A
authors.initials: A
authors.lastname: Mangia
authors.forename: A
authors.initials: A
authors.lastname: Andriulli
authors.forename: M
authors.initials: M
authors.lastname: Puoti
authors.forename: A
authors.initials: A
authors.lastname: Spadaro
authors.forename: M
authors.initials: M
authors.lastname: Freni
authors.forename: V
authors.initials: V
authors.lastname: Di Marco
authors.forename: L
authors.initials: L
authors.lastname: Cino
authors.forename: G
authors.initials: G
authors.lastname: Saracco
authors.forename: A
authors.initials: A
authors.lastname: Chiesa
authors.forename: A
authors.initials: A
authors.lastname: Crosignani
authors.forename: N
authors.initials: N
authors.lastname: Caporaso
authors.forename: F
authors.initials: F
authors.lastname: Morisco
authors.forename: M G
authors.initials: MG
authors.lastname: Rumi
authors.forename: A
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000627:therapeutic use*; D017211:Treatment Failure; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D012254:Ribavirin; D005723:gamma-Glutamyltransferase