6533b829fe1ef96bd1289af1

RESEARCH PRODUCT

Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data.

Savino BrunoV. Di MarcoA. ChiesaMaria Grazia RumiAndrea CrosignaniAngelo AndriulliFilippo SchepisL CinoFreni MaPietro AndreoneNicola CaporasoAnnagiulia GramenziCalogero CammàGiorgio Maria SaraccoO. Lo IaconoAldo SpadaroMassimo PuotiAntonio CraxìFilomena MoriscoAlessandra Mangia

subject

HCV interferon ribavirinAdultMalemedicine.medical_specialtyCombination therapymedicine.medical_treatmentAlpha interferonGastroenterologyAntiviral AgentsDrug Administration Schedulechemistry.chemical_compoundDrug TherapyInternal medicineRibavirinmedicineHumansImmunologic FactorsTreatment FailureChronicAdverse effectChemotherapyAdult; Antiviral Agents; Chi-Square Distribution; Drug Administration Schedule; Drug Therapy; Combination; Female; Hepatitis C; Chronic; Humans; Immunologic Factors; Interferon-alpha; Logistic Models; Male; Middle Aged; Ribavirin; Treatment Failure; gamma-GlutamyltransferaseChi-Square Distributionbusiness.industryRibavirinLiver DiseaseGastroenterologyInterferon-alphaHepatitis Cgamma-GlutamyltransferaseHepatitis C ChronicMiddle Agedmedicine.diseaseHepatitis CConfidence intervalhumanitiesSurgeryLogistic ModelschemistryTolerabilityCombinationDrug Therapy CombinationFemalebusiness

description

Background and aims: Retreatment with a combination of α 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 γ-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 γ-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%.

yearjournalcountryeditionlanguage
2002-12-01
http://hdl.handle.net/11588/135160