GENEVA—A recent trial shows that eltrombopag can, with minimal toxicity, improve platelet levels and reduce bleeding in patients with chronic idiopathic thrombocytopenic purpura (ITP).
The phase 3, randomized, controlled trial evaluated the safety and efficacy of eltrombopag treatment in patients with chronic idiopathic thrombocytopenic purpura (ITP).
James B. Bussel, MD, from Weill Medical College of Cornell University in New York, presented the results at the recent meeting of the International Society on Thrombosis and Haemostasis.
A phase 1 study, reported in a 2007 issue of Blood, administered eltrombopag in active doses of 30, 50, and 75 mg. In normal volunteers, it takes a week for platelet counts to increase. Although increases were seen at all 3 dose levels, the optimal dose of 50 mg was chosen for subsequent studies.
In the phase 3 study, patients were randomized to receive placebo (n=38) or 50 mg of eltrombopag (n=76) once daily for 6 weeks (dose increase to 75 mg allowed). Investigators assessed bleeding according to the World Health Organization bleeding scale.
At the end of treatment (day 43), there was a significant increase in platelet levels in the eltrombopag arm vs the placebo arm. The median platelet count at the end of study was 18,000/μL in the placebo arm and 69,000/μL in the eltrombopag arm. The endpoint of >50,000 platelets/μL was reached in up to 42 days of dosing.
Eighteen out of 76 patients achieved platelet increases to >200,000/μL. The platelet counts fell 2 weeks after the end of therapy. There was a reduction in grade 2/4 bleeding of 18% in the placebo arm, and there were no specific findings of adverse events.
Platelet antibodies are still present as platelet levels fall after the cessation of therapy. Dr Bussel said this study confirmed previous findings with eltrombopag. Treatment not only increased platelet levels, but was able to reduce bleeding.
ITP results in reduced production of marrow platelets and platelet destruction by antibodies. Treatment of ITP is necessary to avoid major bleeding by increasing platelets to >50,000/μL. Eltrombopag is a small molecule, can be used orally, binds to a different region of receptor than thrombopoietin, and signals through the JAK/STAT pathway.
