Spotlight on eltrombopag in treatment-refractory chronic primary immune thrombocytopenia

Eltrombopag (Revolade®) is an orally bioavailable, low molecular weight, synthetic nonpeptide thrombopoietin receptor agonist, which selectively binds to the transmembrane and juxtamembrane domains of the thrombopoietin receptor on the surface of platelets, megakaryocytes, and megakaryocyte precursor cells, resulting in responses similar to those induced by recombinant human thrombopoietin. Eltrombopag does not compete with thrombopoietin for its binding domain on the thrombopoietin receptor, and is highly selective. This article provides an overview of the pharmacological properties of eltrombopag and reviews the clinical efficacy and tolerability of the drug in adult patients with chronic primary immune thrombocytopenia (ITP). In well designed 6-week and 6-month trials, eltrombopag was more effective than placebo at increasing platelet count and decreasing the incidence of bleeding in patients with treatment-refractory chronic ITP, and was generally well tolerated in these patients. Long-term (median duration 100 weeks) data from a noncomparative trial support these results. Importantly, previous splenectomy did not appear to have an effect on the efficacy of eltrombopag. As the first licensed oral thrombopoietin receptor agonist, eltrombopag may be a more convenient option than other ITP medications; however, it may be a costly option long term, as platelet counts generally return to baseline levels following treatment cessation, implying that continued treatment may be advised. Long-term treatment is often necessary in patients with chronic ITP, as curative rates with any treatment are very low. Eltrombopag was generally well tolerated in clinical trials in patients with chronic ITP. Hepatobiliary abnormalities occurred in a greater proportion of eltrombopag than placebo recipients; however, these were usually mild and reversible. Other potential concerns, such as thromboembolic events, cataracts, and increased bone marrow reticulin, need to be further investigated. Eltrombopag is an effective treatment option for adult patients with chronic ITP and an increased risk of bleeding who are refractory to previous treatments, including splenectomy, as demonstrated in well designed clinical trials.