title: Ketoprofen, peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C: a phase II study.
abstract: OBJECTIVE
  To evaluate the safety of adding ketoprofen to pegylated-interferon (PEG-IFN) with or without ribavirin and the effect on viral kinetics, STAT1 activity and expression of 2'-5'-oligoadenylate synthetase (2'-5'OAS) in genotype 1 chronic hepatitis C in a phase II study.
  
  
  METHODS
  Forty-five patients were studied: fifteen were randomized to PEG-IFN plus ribavirin (PR), 16 to PEG-IFN plus ketoprofen and 14 to PR and ketoprofen. The molecular study of IFN-dependent signal transduction was conducted in 9 patients from each group.
  
  
  RESULTS
  The combination of ketoprofen and PEG-IFN with or without ribavirin was safe and well tolerated. An early activation of STAT1 was observed in ketoprofen-treated patients, but this activation was less sustained over time. Conversely, ketoprofen plus PEG-IFN and ribavirin induced an early and sustained increase of 2'-5'OAS transcription starting 24 h after the first dose until the 36th wk. These data are consistent with the clinical results, showing a better sustained virological response and a lower relapse rate in patients receiving ketoprofen plus PEG-IFN and ribavirin.
  
  
  CONCLUSIONS
  The addition of ketoprofen to the standard therapy of chronic hepatitis C should be explored in larger randomized clinical studies.
authors.affiliation: Department of Clinical Medicine, University of Bologna, 40138 Bologna, Italy.
authors.forename: Annagiulia
authors.initials: A
authors.lastname: Gramenzi
authors.forename: Carmela
authors.initials: C
authors.lastname: Cursaro
authors.forename: Marzia
authors.initials: M
authors.lastname: Margotti
authors.forename: Clara
authors.initials: C
authors.lastname: Balsano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Spaziani
authors.forename: Simona
authors.initials: S
authors.lastname: Anticoli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Loggi
authors.forename: Maddalena
authors.initials: M
authors.lastname: Salerno
authors.forename: Silvia
authors.initials: S
authors.lastname: Galli
authors.forename: Giuliano
authors.initials: G
authors.lastname: Furlini
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007660:Ketoprofen / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D011092:Polyethylene Glycols; D012254:Ribavirin; D007660:Ketoprofen; D015088:2',5'-Oligoadenylate Synthetase; C100416:peginterferon alfa-2a