Maria Florencia Tanaka¹, Naval Gustad Daver¹ and Lawrence Rice^1,2

¹Baylor College of Medicine, Houston Texas, USA. ²Weill Cornell Medical College, The Methodist Hospital, Houston Texas, USA.

Abstract

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the production of antibodies to  circulating platelets. Traditionally it has been regarded as a disorder of increased platelet destruction, so therapies have targeted this mechanism, including corticosteroids, IVIG, splenectomy and rituximab. More recently, it has become clear that decreased platelet  production importantly contributes to the thrombocytopenia. The isolation of thrombopoietin (TPO), the ligand for the mpl receptor and the major hormone regulating platelet production, has shed new light on platelet homeostasis and facilitated the development of new therapeutic approaches. First generation TPO-mimetics were removed from clinical trials when some healthy volunteers and patients with cancer developed antibodies against these drugs that cross-reacted with native TPO, causing paradoxical thrombocytopenia. Two second  generation TPO-mimetics, romiplostim and eltrombopag, share no structural homology with endogenous TPO and are being studied in a variety of thrombocytopenic states. Romiplostim was approved by the US FDA in August 2008 for the treatment of patients with ITP who had failed at least one prior therapy. This was based on randomized, placebo-controlled phase III studies that showed increased platelet counts in more than 80% of treated patients, with a durable platelet response by stringent criteria in 38% of splenectomized and 61% of non-splenectomized patients compared to 0%–5% in patients receiving placebo. Being non-immunosuppressive, the toxicity profile is favorable, although there are concerns with this class of drugs with thrombotic risks, “rebound thrombocytopenia,” marrow reticulin fibrosis, or even hematopoietic clonal proliferation. Romiplostim may gain an increasing niche in the treatment of ITP.