Immune thrombocytopenic purpura is an autoimmune disease (app. 100 cases / 1 million people/year) characterized by platelet destruction caused by auto-antibodies. In normal haematopoiesis, the liver produces thrombopoietin (TPO), which stimulates megakaryocytes via the thrombopoietin receptor (also known as cMpl) and activates a signal transduction pathway via the tyrosine kinase Janus 2 (JAK2) and STAT5. This results in megakaryocyte proliferation, differentiation and platelet production.

Romiplostim - possessing a recombinant TPO receptor binding domain - is able to activate the same pathway as the endogenous TPO, although there is no amino acid sequence homology. The subsequent increase in platelet production outpaces the rate of platelet destruction by the disease.

Romiplostim (59 KDa) is a recombinant fusion protein composed of two subunits, each consisting of a human immunoglobulin IgG1 Fc domain linked to a peptide chain containing two thrombopoietin receptor binding domains. The coupling with the Fc region prolongs half-life and is designed to prevent the formation of TPO cross-reacting antibodies.The goal of romiplostim therapy is to reduce serious bleeding events, not to achieve normal thrombocyte counts. Compared to placebo, romiplostim lowered the frequency of serious bleeding

events (grade 2 and 3) in ITP patients. The overall incidence of bleeding was not significantly altered by romiplostim compared to placebo.

Increased bone marrow reticulin, the main risk following romiplostim therapy, is probably due to TPO receptor stimulation at the megakaryocytes. Bone marrow abnormalities such as fibrosis and blood cell abnormalities might be the result. Therefore, monitoring of the peripheral blood smear and complete blood count should be performed. The most frequent treatment-related adverse effects include headache, myalgia, fatigue, and arthralgia. Other risks which require close monitoring are thrombocythemia and thromboembolic events, malignancies, immunogenicity and effects on renal function. Bleeding should be considered as a result ineffective romiplostim therapy. Recurrence of thrombocytopenia after discontinuation of romiplostim can be expected.

Romiplostim is indicated for the treatment of thrombocytopenia in patients with immune thrombocytopenic purpura (ITP) who have been shown to be unresponsive to traditional treatments such as corticosteroids and immunoglobulins or splenectomy. Romiplostim might as well be effective in cancer and liver patients suffering from thrombocytopenia.

EPAR of romiplostim.