Document Type
Article
Original Publication Date
2007
Journal/Book/Conference Title
The New England Journal of Medicine
Volume
357
DOI of Original Publication
10.1056/NEJMoa073255
Date of Submission
January 2015
Abstract
Background
Eltrombopag is a new, orally active thrombopoietin-receptor agonist that stimulates thrombopoiesis. We evaluated its ability to increase platelet counts and facilitate treatment for hepatitis C virus (HCV) infection in patients with thrombocytopenia associated with HCV-related cirrhosis.
Methods
Seventy-four patients with HCV-related cirrhosis and platelet counts of 20,000 to less than 70,000 per cubic millimeter were randomly assigned to receive eltrombopag (30, 50, or 75 mg daily) or placebo daily for 4 weeks. The primary end point was a platelet count of 100,000 per cubic millimeter or more at week 4. Peginterferon and ribavirin could then be initiated, with continuation of eltrombopag or placebo for 12 additional weeks.
Results
At week 4, platelet counts were increased to 100,000 per cubic millimeter or more in a dose-dependent manner among patients for whom these data were available: in 0 of the 17 patients receiving placebo, in 9 of 12 (75%) receiving 30 mg of eltrombopag, in 15 of 19 (79%) receiving 50 mg of eltrombopag, and in 20 of 21 (95%) receiving 75 mg of eltrombopag (P<0.001). Antiviral therapy was initiated in 49 patients (in 4 of 18 patients receiving placebo, 10 of 14 receiving 30 mg of eltrombopag, 14 of 19 receiving 50 mg of eltrombopag, and 21 of 23 receiving 75 mg of eltrombopag) while the administration of eltrombopag or placebo was continued. Twelve weeks of antiviral therapy, with concurrent receipt of eltrombopag or placebo, were completed by 36%, 53%, and 65% of patients receiving 30 mg, 50 mg, and 75 mg of eltrombopag, respectively, and by 6% of patients in the placebo group. The most common adverse event during the initial 4 weeks was headache; thereafter, the adverse events were those expected with interferon-based therapy.
Conclusions
Eltrombopag therapy increases platelet counts in patients with thrombocytopenia due to HCV-related cirrhosis, thereby permitting the initiation of antiviral therapy. (ClinicalTrials.gov number, NCT00110799.)
Rights
From The New England Journal of Medicine, McHutchison, J. G., Dusheiko, G., Shiffman, M. L. et al., Eltrombopag for Thrombocytopenia in Patients with Cirrhosis Associated with Hepatitis C, Vol. 357, Page 2227, Copyright © 2007 Massachusetts Medical Society. Reprinted with permission.
Is Part Of
VCU Medical Center Publications
Comments
Originally Published at http://dx.doi.org/10.1056/NEJMoa073255
This article has been updated on March 6, 2008 at NEJM.org. The correction was published in response to a letter to the editor as follows:
Dr. McHutchison replies: Lawson cites the report by Heathcote et al., which indicates that only 2 to 4% of patients treated with peginterferon alfa-2a required a dose reduction for thrombocytopenia.1 That study, however, excluded patients with baseline platelet counts of less than 75,000 per cubic millimeter and hence does not represent the population studied in our trial or the population targeted in ongoing trials.
Of the five patients with baseline platelet counts that were 70,000 or more per cubic millimeter (with the numbers according to study group listed correctly in Table 1 of our article but incorrectly in the legend for Fig. 1), three initiated and completed the antiviral therapy phase (one in the 30-mg group and two in the 75-mg group). Two patients did not enter the antiviral therapy phase: one (in the 30-mg group) did not enter this phase because of an adverse event, and one (in the placebo group) had insufficient platelets for initiation of antiviral therapy.
John G. McHutchison, M.D. Duke Clinical Research Institute, Durham, NC 27715 mchut001@mc.duke.edu