Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy.
Abstract | BACKGROUND & AIMS: 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.
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Authors | 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 |
Journal | Gastroenterology
(Gastroenterology)
Vol. 146
Issue 2
Pg. 442-52.e1
(Feb 2014)
ISSN: 1528-0012 [Electronic] United States |
PMID | 24126097
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Antiviral Agents
- Benzoates
- Hematologic Agents
- Hydrazines
- Interferon alpha-2
- Interferon-alpha
- Pyrazoles
- Recombinant Proteins
- Polyethylene Glycols
- Ribavirin
- peginterferon alfa-2b
- peginterferon alfa-2a
- eltrombopag
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antiviral Agents
(therapeutic use)
- Benzoates
(therapeutic use)
- Drug Administration Schedule
- Female
- Follow-Up Studies
- Hematologic Agents
(therapeutic use)
- Hepatitis C, Chronic
(blood, complications, drug therapy)
- Humans
- Hydrazines
(therapeutic use)
- Induction Chemotherapy
- Intention to Treat Analysis
- Interferon alpha-2
- Interferon-alpha
(therapeutic use)
- Liver Cirrhosis
(blood, complications, virology)
- Maintenance Chemotherapy
- Male
- Middle Aged
- Platelet Count
- Polyethylene Glycols
(therapeutic use)
- Pyrazoles
(therapeutic use)
- Recombinant Proteins
(therapeutic use)
- Ribavirin
(therapeutic use)
- Thrombocytopenia
(blood, drug therapy, virology)
- Treatment Outcome
- Young Adult
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