Novel treatments in the management of immune thrombocytopenic purpura (ITP)

Abstract

ITP is generally considered an antibody mediated condition with platelet destruction characterised by an abnormally low platelet count. More recently it has also been shown that insufficient or inadequate platelet production also plays a role. Less than 10% with chronic ITP experience spontaneous remission and need long-term management. Conventional first line management is with corticosteroids or intravenous immune globulins (including anti-D) followed by a variety of agents including cytotoxic and immune suppressive agents for refractory and relapsed patients. Splenectomy may also be considered but one-third fail to respond. However, up to 50% of the mortality seen in ITP is due to infection secondary to immune suppression and treatment is generally unsatisfactory. In view of the recognised suboptimal platelet production there has been a search for treatments that enhance platelet production. The identification of thrombopoietin, the key regulator of megakaryopoiesis, in 1994, led to its evaluation in ITP. The first studies were discontinued because of the development of cross-reacting antibodies, leading to severe thrombocytopenia. Nevertheless, this paved the way for the development of the next generation of agents, including the peptibody, romiplostim and the small-molecule TPO receptor agonist, eltrombopag. Both showed promising results in early studies, confirmed in Phase III clinical trials, and are now being evaluated for their place in the treatment pathway.