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Effects of Eltrombopag On Thrombopietin Levels During Antiviral Therapy in HCV Patients with Cirrhosis
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Reported by Jules Levin
DDW, May 21, 2008, San Diego
Nezam Afdhal1, John G McHutchison2, Fiona M Campbell3, James B Bussel4, Gregory Cheng5, Nicole Blackman6, Julian M Jenkins6, Dickens Theodore7
1. Beth Israel Deaconess Medical Center, Boston, MA, USA, 2. Duke University and Duke Clinical Research Institute, Durham, NC, USA, 3. GlaxoSmithKline, Stockley Park, United Kingdom, 4. Weill Medical College of Cornell University, New York, NY, USA, 5. Prince of Wales Hospital, Shatin, China, 6. GlaxoSmithKline, Collegeville, PA, USA, 7. GlaxoSmithKline, Research Triangle Park, NC, USA
ABSTRACT from program book
Background and Aims: Thrombocytopenia is common in advanced liver disease and may be partially caused by inadequate TPO production by liver cells. Previous reports indicate that cirrhotic HCV patients have lower than normal TPO levels and a blunted TPO response to interferon-induced thrombocytopenia. Eltrombopag, a non-peptide platelet growth factor, increases platelet counts in chronic HCV patients and allows initiation and maintenance of pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy (McHutchison, NEJM 2007). We report an analysis of serum TPO levels in thrombocytopenic patients receiving eltrombopag treatment.
Methods: Baseline and on-treatment serum TPO levels were quantified by Quest Diagnostics using an ELISA (R&D Systems, Cat# DTP00B) in cirrhotic subjects with HCV (n=63) and non-cirrhotic subjects (eltrombopag-treated healthy volunteers [n=43], idiopathic thrombocytopenic purpura [ITP], n=87). In HCV subjects, TPO levels were examined during treatment with eltrombopag alone (30, 50 and 75mg) or placebo, and during subsequent concurrent eltrombopag and antiviral therapy (PEG-IFN/RBV).
Results: HCV patients were similar across treatment groups with respect to age (range 30- 74y), race (89% Caucasian), baseline platelet count (range 27-94Gi/L), and liver tests (ALT, AST, albumin). Baseline TPO levels in HCV patients were lower than those observed in other populations (median [range] TPO levels: HCV, 33ng/L [25-89]; ITP, 55ng/L [26-605]; healthy volunteers, 62ng/L [0-93]).
When administered alone, eltrombopag increased platelet counts, but did not affect TPO levels in cirrhotic and noncirrhotic patients. After 8 weeks of concurrent treatment with eltrombopag and PEG-IFN/RBV, HCV patients experienced an increase in TPO levels (median [range], 60ng/L [25-169]).
Conclusions: Baseline serum TPO levels were lower in HCV subjects with thrombocytopenia than in noncirrhotic subjects (ITP and healthy subjects). When eltrombopag was administered alone to HCV subjects, TPO levels were not affected. This was also true for ITP and healthy subjects. However, TPO levels increased in HCV patients administered eltrombopag in combination with PEG-IFN/RBV. In contrast, Peck-Radosavjevic et al. (Hepatology, 1998) showed that IFN-induced thrombocytopenia resulted in increased TPO levels in noncirrhotic HCV subjects but did not result in increased TPO levels in cirrhotic HCV subjects. These results suggest that eltrombopag may correct the blunted TPO response to IFN-induced thrombocytopenia.
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