Ketoprofen, peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C: a phase II study.
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.
Gramenzi
Annagiulia
A
Department of Clinical Medicine, University of Bologna, 40138 Bologna, Italy.
Cursaro
Carmela
C
Margotti
Marzia
M
Balsano
Clara
C
Spaziani
Alessandra
A
Anticoli
Simona
S
Loggi
Elisabetta
E
Salerno
Maddalena
M
Galli
Silvia
S
Furlini
Giuliano
G
Bernardi
Mauro
M
Andreone
Pietro
P
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
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