Emerging strategies to treat chronic immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is a fairly common hematological disorder and is a minor disease for many affected patients; most are in good health, and many can tolerate low platelet counts without the need for treatment. For the majority of patients who do undergo treatment, first-line therapies, including corticosteroids, are effective in increasing platelet counts, although long-term use can be associated with adverse effects. Second-line therapies, such as immunosuppressants, have been largely untested in controlled studies of ITP patients. Like first-line therapies, splenectomy is effective for many patients; however, it is frequently avoided by physicians who prefer the use of alternative drug therapies due to concerns about safety risks and is often declined by patients reluctant to undergo surgery. Thus, approaches to avoid or defer the use of splenectomy have been actively pursued. An anti-CD20 antibody, rituximab, can limit the production of autoantibodies, but reactivated viral infections have been reported with its use. Agents that directly stimulate platelet production, such as thrombopoietin (TPO) receptor-binding agents, have shown promise in clinical trials of ITP patients as well as in hepatitis C virus-infected individuals with thrombocytopenia. Two TPO receptor agonists in advanced clinical development--eltrombopag and AMG 531--are discussed here. Both eltrombopag and AMG 531 appear to be effective in raising platelet counts and both have been well tolerated in clinical trials to date. However, potential safety issues with thrombopoietic growth factors include thrombocytosis, rebound thrombocytopenia, and increased bone marrow fibrosis. Further testing will determine which safety issues--if any--are of clinical concern.