A research team from Italy conducted a phase II study evaluating the molecular and clinical effect of ketoprofen plus pegylated interferon with or without ribavirin in patients with genotype 1 chronic hepatitis C. Their results on hepatitis C virus kinetics and interferon signaling, together with the efficacy and safety data, offer the rationale to further explore this three-drug combination in chronic hepatitis C, especially in difficult to treat patients.
The current standard treatment for chronic hepatitis C with pegylated-interferon (PEG-IFN) and ribavirin is effective in approximately 50%-60% of patients, so that a substantial proportion of patients remain unresponsive. A rational approach to develop alternative therapeutic strategies for patients with chronic hepatitis C virus (HCV) infection demands a detailed knowledge of how the different drugs affect viral kinetics and IFN intracellular signaling. Non-steroidal antiinflammatory drugs (NSAIDs) have been demonstrated to amplify the IFN signaling pathways and to enhance the anti-viral effect of IFN.
Based on previous data, a research team from Italy evaluated the safety of adding ketoprofen to pegylated-interferon (PEG-IFN) with or without ribavirin and the effect on viral kinetics, signal transducer and activator of transcription 1 (STAT1) activity and expression of 2'-5'-oligoadenylate synthetase (2'-5'OAS) in genotype 1 chronic hepatitis C in a phase Ⅱ study. Their study will be published on December 21, 2009 in the World Journal of Gastroenterology.
Their research found that the addition of ketoprofen to the conventional combination therapy is associated with better viral kinetics and early activation of the IFNa signaling pathway, thus improving virological response rates. The authors postulated that a larger trial should be done with this three-drug combination, compared to the standard of care.
- Gramenzi A, Cursaro C, Margotti M, Balsano C, Spaziani A, Anticoli S, Loggi E, Salerno M, Galli S, Furlini G, Bernardi M, Andreone P. Ketoprofen, peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C: A phase II study. World Journal of Gastroenterology, 2009; 15 (47): 5946 DOI: 10.3748/wjg.15.5946
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