Brief Article
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Dec 21, 2009; 15(47): 5946-5952
Published online Dec 21, 2009. doi: 10.3748/wjg.15.5946
Ketoprofen, peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C: A phase II study
Annagiulia Gramenzi, Carmela Cursaro, Marzia Margotti, Clara Balsano, Alessandra Spaziani, Simona Anticoli, Elisabetta Loggi, Maddalena Salerno, Silvia Galli, Giuliano Furlini, Mauro Bernardi, Pietro Andreone
Annagiulia Gramenzi, Carmela Cursaro, Marzia Margotti, Elisabetta Loggi, Mauro Bernardi, Pietro Andreone, Department of Clinical Medicine, University of Bologna, 40138 Bologna, Italy
Clara Balsano, Alessandra Spaziani, Simona Anticoli, Molecular Virology and Oncology Laboratory, “A. Cesalpino” Foundation, University of Rome “La Sapienza”, 00161 Rome, Italy
Clara Balsano, Department of Internal Medicine, University of L’Aquila, 67100 L’Aquila, Italy
Maddalena Salerno, Hepatology Outpatient Clinic, Hospital of Paola, 87027 Paola (CS), Italy
Silvia Galli, Giuliano Furlini, Department of Hematology, Oncology and Laboratory Medicine, S.Orsola-Malpighi Hospital, 40138 Bologna, Italy
Author contributions: Gramenzi A designed the research, analyzed the data and wrote the paper; Cursaro C coordinated the clinical part of the study and participated in the development of the protocol; Margotti M coordinated the laboratory investigation and was responsible for IRB procedures; Balsano C contributed to the study design and supervised the laboratory molecular research; Spaziani A and Anticoli S were responsible for the laboratory molecular study; Loggi E collected laboratory data; Salerno M collected clinical data; Galli S and Furlini G were responsible for the virological assays; Bernardi M supervised and critically reviewed the manuscript; Andreone P conceived the study, supervised its realization and was responsible for the final approval of the manuscript; all authors read and approved the final manuscript.
Correspondence to: Pietro Andreone, Professor, Department of Clinical Medicine, University of Bologna, via Massarenti 9, 40138 Bologna, Italy.
Telephone: +39-51-6363618 Fax: +39-51-345806
Received: July 23, 2009
Revised: September 12, 2009
Accepted: September 19, 2009
Published online: December 21, 2009

AIM: 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.

CONCLUSION: The addition of ketoprofen to the standard therapy of chronic hepatitis C should be explored in larger randomized clinical studies.

Keywords: Liver, Viral hepatitis, Chronic hepatitis C, Clinical pharmacology, Non-steroidal antiinflammatory drugs