Eltrombopag increases platelet numbers in thrombocytopenic patients with hcv infection and cirrhosis, allowing for effective antiviral therapy

Nezam H. Afdhal, Geoffrey M. Dusheiko, Edoardo G. Giannini, Pei Jer Chen, Kwang Hyub Han, Aftab Mohsin, Maribel Rodriguez-Torres, Sorin Rugina, Igor Bakulin, Eric Lawitz, Mitchell L. Shiffman, Ghias Un Nabi Tayyab, Fred Poordad, Yasser Mostafa Kamel, Andres Brainsky, James Geib, Sandra Y. Vasey, Rita Patwardhan, Fiona M. Campbell, Dickens Theodore

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Abstract

Background & Aims Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV. Methods Patients with HCV infection and thrombocytopenia (platelet count <75,000/μL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients whose platelet counts reached the predefined minimal threshold for the initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were assigned randomly (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary end point was sustained virologic response (SVR) 24 weeks after completion of antiviral therapy. Results More patients who received eltrombopag than placebo achieved SVRs (ENABLE-1: eltrombopag, 23%; placebo, 14%; P =.0064; ENABLE-2: eltrombopag, 19%; placebo, 13%; P =.0202). PEG was administered at higher doses, with fewer dose reductions, in the eltrombopag groups of each study compared with the placebo groups. More patients who received eltrombopag than placebo maintained platelet counts of 50,000/μL or higher throughout antiviral treatment (ENABLE-1, 69% vs 15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%) and thromboembolic events, which were more common in the eltrombopag group of ENABLE-2. Conclusions Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise ineligible or marginal patients to begin and maintain antiviral therapy, leading to significantly increased rates of SVR. Clinical trial no: NCT00516321, NCT00529568.

Original languageEnglish
Pages (from-to)442-452.e1
JournalGastroenterology
Volume146
Issue number2
DOIs
Publication statusPublished - 2014 Feb

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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    Afdhal, N. H., Dusheiko, G. M., Giannini, E. G., Chen, P. J., Han, K. H., Mohsin, A., Rodriguez-Torres, M., Rugina, S., Bakulin, I., Lawitz, E., Shiffman, M. L., Tayyab, G. U. N., Poordad, F., Kamel, Y. M., Brainsky, A., Geib, J., Vasey, S. Y., Patwardhan, R., Campbell, F. M., & Theodore, D. (2014). Eltrombopag increases platelet numbers in thrombocytopenic patients with hcv infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology, 146(2), 442-452.e1. https://doi.org/10.1053/j.gastro.2013.10.012