Eltrombopag: An oral thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura

Background: Idiopathic thrombocytopenic purpura (ITP) is a relatively rare acquired autoimmune disease characterized by either decreased platelet production or increased platelet destruction leading to reduced platelet counts and increased risk of bleeding. Immune modulators have been used in treatment; however, a novel class of thrombopoietin mimetics has recently been developed. Eltrombopag is approved for patients with chronic ITP who have failed initial treatments with traditional immune modulators or splenectomy. Objectives: The goals of this review were to summarize the pharmacology, pharmacokinetic properties, efficacy, and tolerability of eltrombopag and review the approved and investigational uses of this drug. Methods: A search of Cochrane Central Register of Clinical Trials and clinicaltrials.gov was conducted using the terms eltrombopag or SB-497115-GR. In addition, all reviews and preclinical and clinical studies published in English between January 1980 and January 2011 were identified in PubMed and Cochrane Database of Systemic Reviews using the same terms. Results: A total of 153 publications and 13 clinical trials were identified; 14 publications were excluded because they were not published in English. A Phase III trial randomized 114 patients with ITP 2:1 to eltrombopag 50 mg or placebo and demonstrated by day 43 a significantly greater proportion of patients responding in the eltrombopag group than in the placebo group (59% vs 16%, odds ratio [OR] = 9.61; 95% CI, 3.31-27.86; P < 0.0001). The mean percentage change of platelets from baseline in the eltrombopag group was double that of the placebo group at day 8 and was sustained several-fold higher throughout the remainder of the treatment period. Another Phase III trial evaluated the efficacy and safety of eltrombopag compared with placebo over 6 months. The odds of responding (defined as a platelet count of 50-400 × 10 ⁹/L) were 8 times higher in patients receiving eltrombopag than in those in the placebo group (95% CI, 3.59-18.73; P < 0.0001). Bone marrow fibrosis and hepatotoxicity are the most serious adverse effects, and nausea and vomiting are the most common. Eltrombopag is also being evaluated in the treatment of thrombocytopenia secondary to hepatitis C infection, chemotherapy, acute leukemia, and myelodysplasias. Conclusion: Eltrombopag is well tolerated and effective in raising platelet counts in patients with chronic ITP.