Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C.
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.)
McHutchison
John G
JG
Duke University and Duke Clinical Research Institute, Durham, NC 27705, USA. mchut001@mc.duke.edu
Dusheiko
Geoffrey
G
Shiffman
Mitchell L
ML
Rodriguez-Torres
Maribel
M
Sigal
Samuel
S
Bourliere
Marc
M
Berg
Thomas
T
Gordon
Stuart C
SC
Campbell
Fiona M
FM
Theodore
Dickens
D
Blackman
Nicole
N
Jenkins
Julian
J
Afdhal
Nezam H
NH
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011994:Recombinant Proteins; D013921:Thrombocytopenia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology
D000998:Antiviral Agents; D001565:Benzoates; D006834:Hydrazines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a; C520809:eltrombopag