TY - JOUR
T1 - Eltrombopag increases platelet numbers in thrombocytopenic patients with hcv infection and cirrhosis, allowing for effective antiviral therapy
AU - Afdhal, Nezam H.
AU - Dusheiko, Geoffrey M.
AU - Giannini, Edoardo G.
AU - Chen, Pei Jer
AU - Han, Kwang Hyub
AU - Mohsin, Aftab
AU - Rodriguez-Torres, Maribel
AU - Rugina, Sorin
AU - Bakulin, Igor
AU - Lawitz, Eric
AU - Shiffman, Mitchell L.
AU - Tayyab, Ghias Un Nabi
AU - Poordad, Fred
AU - Kamel, Yasser Mostafa
AU - Brainsky, Andres
AU - Geib, James
AU - Vasey, Sandra Y.
AU - Patwardhan, Rita
AU - Campbell, Fiona M.
AU - Theodore, Dickens
N1 - Funding Information:
Funding These studies ( NCT00516321 and NCT00529568 , available at www.clinicaltrials.gov ) were funded by GlaxoSmithKline. Editorial support in the development of the manuscript was provided by Ted Everson and Nancy Price of AOI Communications and was funded by GlaxoSmithKline.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - Blood Clot
KW - Complication
KW - Liver Disease
KW - Portal Hypertension
UR - http://www.scopus.com/inward/record.url?scp=84892769466&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892769466&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2013.10.012
DO - 10.1053/j.gastro.2013.10.012
M3 - Article
C2 - 24126097
AN - SCOPUS:84892769466
SN - 0016-5085
VL - 146
SP - 442-452.e1
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -