Optimized peg-interferon alpha-2a Treatment of Hepatitis C and Hepatitis B

Optimized peg-interferon alpha-2a Treatment of Hepatitis C and Hepatitis B

The funding for the PhD project is provided jointly be the Centre for Bayesian Statistics in Health Economics (CHEBS) and the School of Mathematics and Statistics (SoMaS) at the University Of Sheffield.

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are serious global health problems. According to WHO fact sheets, 2 billion people infected HBV worldwide, and 350 million suffering from chronic HBV infection. Similarly, HCV infection has an estimated prevalence of 2.35 per cent in 2011 (160 million chronically infected individuals).

Peg-interferon alpha-2a (Peg-IFN-a 2a) is effective antiviral drug for chronic liver diseases. However, it is associated with a number of side effects, including mild thrombocytopenia. The usual protocol to treat Peg-IFN-a 2a related thrombocytopenia is to reduce the Peg-IFN-a 2a dose if platelet count falls to < 30 × 109/L. Interferon therapy should be discontinued if platelet count falls to < 20 × 109/L. This leads to dose modification in approximately 19% of cases and discontinuation in 2% of cases. Peg-IFN-a 2a combined with a low dose of ribavirin is more effective than conventional interferon combined with a low dose of ribavirin. However, a significant number of patients fail to respond to respond to Peg-IFN-a 2a.

The objective of the present project is to develop an optimal dosing algorithm of Peg-IFN-a 2a. Two models will be formulated: 1) A model that describe the antiviral response to Peg-IFN-a 2a treatment (described using various response markers such as aminotransferase levels, antigen-antibody HBV profile, and viral load) and 2) A model that describe the change in platelet level following Peg-IFN-a 2a treatment. These models will be used to will identify the pharmacokinetic /pharmacodynamic (PK/PD) and physiologic factors important in predicting and maximizing Peg-IFN-a 2a’s effect in the treatment of Hepatitis B and Hepatitis C infections. We also identify factors that minimize the incidence of thrompocytopenia and hence avoid Peg-IFN-a 2a dose reduction or discontinuation. The model can also be used to identify predictors of non-responders to Peg-IFN-a 2a treatment so early measures can be taken to improve therapeutic outcomes. This project is expected to improve patient care by identifying proper treatment strategies and (sub)populations that may (or may not) benefit from Peg-IFN-a 2a. Additionally, and hence avoid antiviral therapy discontinuation.

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Medicine: peg-interferon alpha-2a, Condition: chronic hepatitis b, Phase: 2, Clinical Study ID: NV16037, Sponsor: Roche" },{ "PostingID": 1333, "Title": "ROCHE-WV16240", "Description": "A phase III partially double blind study evaluating the efficacy and safety of 40KD branched pegylated interferon alfa-2a (PEG-IFN, RO0258310) combined with placebo or lamivudine versus lamivudine in HBeAg positive patients with chronic hepatitis B

Medicine: peg-interferon alpha-2a, Condition: chronic hepatitis b, Phase: 3, Clinical Study ID: WV16240, Sponsor: Roche" },{ "PostingID": 1334, "Title": "ROCHE-WV16241", "Description": "A phase III partially double blinded study evaluating the efficacy and safety of 4okD branched pegylated inteferon alfa-2a (PEG-IGFN, Ro 25-8310) combined with placebo or lamivudine versus lamivudine in anti-HBe positive patients with chronic hepatitis B

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