Eltrombopag increases platelet numbers in thrombocytopenic patients with hcv infection and cirrhosis, allowing for effective antiviral therapy
Journal
Gastroenterology
Journal Volume
146
Journal Issue
2
Pages
442-4520
Date Issued
2014
Author(s)
Afdhal N.H.
Dusheiko G.M.
Giannini E.G.
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.
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. ? 2014 by the AGA Institute.
Subjects
Blood Clot; Complication; Liver Disease; Portal Hypertension
SDGs
Other Subjects
aspartate aminotransferase; bilirubin; eltrombopag; hemoglobin; peginterferon alpha2a; peginterferon alpha2b; placebo; ribavirin; adult; aged; anemia; antiviral therapy; article; ascites; aspartate aminotransferase blood level; asthenia; bacterial peritonitis; bilirubin blood level; cataract; chronic liver disease; controlled study; coughing; decompensated liver cirrhosis; decreased appetite; diarrhea; drug dose escalation; drug dose reduction; drug efficacy; drug fatality; drug safety; esophagus varices bleeding; fatigue; female; fever; flu like syndrome; gastroenteritis; gastrointestinal hemorrhage; genotype; headache; hematemesis; hemoglobin blood level; hepatic encephalopathy; hepatitis C; human; hyperbilirubinemia; insomnia; leukocyte count; leukopenia; liver cell carcinoma; liver cirrhosis; liver failure; lymphocytopenia; maintenance therapy; major clinical study; male; middle aged; nausea; neutropenia; neutrophil count; outcome assessment; pancytopenia; pneumonia; portal vein thrombosis; priority journal; pruritus; randomized controlled trial; sepsis; sudden death; thrombocyte count; thrombocytopenia; treatment duration; treatment response; unspecified side effect; upper gastrointestinal bleeding; urinary tract infection; young adult; adverse event; AE; Blood Clot; CI; Complication; confidence interval; early virologic response; Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease; ENABLE; end-of-treatment response; ETR; EVR; HCC; HCV; hepatitis C virus; hepatocellular carcinoma; Liver Disease; patient-year; PEG; peginterferon alfa; Portal Hypertension; portal vein thrombosis; PVT; PY; rapid virologic response; RBV; ribavirin; RVR; SAE; serious adverse event; sustained virologic response; SVR; TCP; TEE; thrombocytopenia; thromboembolic event; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Benzoates; Drug Administration Schedule; Female; Follow-Up Studies; Hematologic Agents; Hepatitis C, Chronic; Humans; Hydrazines; Induction Chemotherapy; Intention to Treat Analysis; Interferon-alpha; Liver Cirrhosis; Maintenance Chemotherapy; Male; Middle Aged; Platelet Count; Polyethylene Glycols; Pyrazoles; Recombinant Proteins; Ribavirin; Thrombocytopenia; Treatment Outcome; Young Adult
Publisher
W.B. Saunders
Type
journal article