Gastroenterology. 2013 Oct 11. pii: S0016-5085(13)01436-4. doi: 10.1053/j.gastro.2013.10.012. [Epub ahead of print]
Afdhal NH, Dusheiko GM, Giannini EG, Chen PJ, Han KH, Mohsin A, Rodriguez-Torres M, Rugina S, Bakulin I, Lawitz E, Shiffman ML, Tayyab GU, Poordad F, Kamel YM, Brainsky A, Geib J, Vasey SY, Patwardhan R, Campbell FM, Theodore D.
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. Electronic address: email@example.com.
BACKGROUND & AIMS: Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-α (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 -2, investigated the ability of eltrombopag to increase numbers of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV.
METHODS: Patients with HCV infection and thrombocytopenia (platelets <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 daily) for ≤9 weeks. Patients whose platelet counts reached the predefined minimal threshold for initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were randomly assigned (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary endpoint 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 platelets ≥50,000/μL 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.
Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS: AEs, CIs, ETR, EVR, HCV, IRs, ITT, PEG, PYs, RBV, RVR, SAEs, SVR, TCP, TEEs, TPO-R, ULN, adverse events, blood clot, cEVR, complete early virologic response, complication, confidence intervals, early virologic response, end of treatment response, hepatitis C virus, incidence rates, intent-to-treat, liver disease, patient years, peginterferon alfa, portal hypertension, rapid virologic response, ribavirin, serious adverse events, sustained virologic response, thrombocytopenia, thromboembolic events, thrombopoietin receptor, upper limit normal
PMID: 24126097 [PubMed - as supplied by publisher]