title: Higher doses of peginterferon alpha-2b administered twice weekly improve sustained virological response in difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized study.
abstract: Beside substantial progress in treatment of chronic hepatitis C (CHC) particular patients (genotype 1/4, high viral load, previous nonresponse, cirrhosis) remain difficult to treat. The aim of our pilot randomized study was to compare efficacy and tolerability of standard doses of Peginterferon alpha-2b + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly + ribavirin. Sixty-five outpatients with CHC were subsequently enrolled. Group A (n = 22) received recommended doses of Peginterferon alpha-2b and group B (n = 43), received high doses twice weekly. Groups were comparable for baseline characteristics. All genotype 1/4 patients had high baseline viraemia. Sustained virological response (SVR) was significantly higher in group B among naïve patients (72%vs 25%, P = 0.024). A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients, (46%vs 13%, P = 0.03) and grouping together genotype 1/4 naive and relapsers (57%vs 11%, P = 0.039). Discontinuation rate was 32% (7 of 22) in group A and 21% (9 [corrected] of 43) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia. Our pilot study supports the need of randomized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha-2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules.
authors.affiliation: Department of Internal Medicine & Gastroenterology, University of Bologna, Bologna, Italy. francesca.lodato@inwind.it
authors.forename: F
authors.initials: F
authors.lastname: Lodato
authors.forename: F
authors.initials: F
authors.lastname: Azzaroli
authors.forename: S
authors.initials: S
authors.lastname: Brillanti
authors.forename: A
authors.initials: A
authors.lastname: Colecchia
authors.forename: M R
authors.initials: MR
authors.lastname: Tamé
authors.forename: M
authors.initials: M
authors.lastname: Montagnani
authors.forename: R
authors.initials: R
authors.lastname: Muratori
authors.forename: S
authors.initials: S
authors.lastname: Giovanelli
authors.forename: V
authors.initials: V
authors.lastname: Feletti
authors.forename: M L
authors.initials: ML
authors.lastname: Bacchi Reggiani
authors.forename: E
authors.initials: E
authors.lastname: Roda
authors.forename: G
authors.initials: G
authors.lastname: Mazzella
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin