Romiplostim: A Novel Thrombopoiesis-stimulating Agent

Sarah Perreault; Julianna Burzynski


Am J Health Syst Pharm. 2009;66(9):817-824. 

In This Article

Abstract and Introduction


Purpose: The pharmacology, pharmacokinetics, dosage and administration, efficacy, safety, effects on quality of life, and place in therapy of romiplostim are reviewed.
Summary: Romiplostim is a second- generation thrombopoietic agent that stimulates the thrombopoietin receptor and platelet production without inducing production of autoantibodies. Romiplostim, a peptibody, bears no structural resemblance to endogenous thrombopoietin, thus minimizing the risk for development of thrombopoietin autoantibodies. Clinical trials have shown that romiplostim increases platelet counts compared with placebo in both splenectomized and non-splenectomized adult patients with chronic idiopathic thrombocytopenic purpura (ITP). Clinical trials with romiplostim are ongoing for patients with myelodysplastic syndrome and those receiving chemotherapy for treatment of malignancies. Romiplostim may confer an increased risk of bone marrow reticulin formation or fibrosis, malignancy, thrombosis, and thrombocytopenia that is more severe than the level present before initiation of romiplostim.
While all patients receiving romiplostim in clinical trials experienced at least one adverse event, most were mild to moderate in severity. The most frequent adverse effects were ecchymosis, headache, and petechiae. Romiplostim is initiated at a dosage of 1 µg/kg subcutaneously once weekly and titrated to achieve platelet counts between 50 and 200 x 109 platelets/L, with a maximum dose of 10 µg/kg. Romiplostim is only available through the manufacturer's risk-management program. The current wholesale price of romiplostim is $1,062.50 for a single-use vial of 250 µg or $2,125 for a single-use vial of 500 µg. The extrapolated drug cost for weekly dosing for one year is approximately $55,250.
Conclusion: Romiplostim is a novel thrombopoietic-stimulating agent for use in patients with chronic ITP who have not responded to other therapies.


Idiopathic (immune) thrombocytopenic purpura (ITP) is an auto-immune disorder characterized by immune-mediated platelet destruction and decreased platelet production.[1] The prevalence of ITP in adults is estimated to be 2 in 100,000 people per year, with a female predominance among middle-aged adults.[2,3] ITP is a diagnosis of exclusion. It is most often diagnosed in healthy individuals with isolated thrombocytopenia, an unremarkable peripheral blood smear, evidence of bleeding on physical examination consistent with the degree of thrombocytopenia, and no underlying source of thrombocytopenia (e.g., drugs or disorder associated with secondary immune thrombocytopenia, family history).[4] The focus of this review is adult ITP, which differs from childhood ITP in that it has a low rate of spontaneous remission and is not associated with viral illnesses or immunization.[5]

Therapy for ITP is generally initiated when the platelet count is < 30 x 109 platelets/L or when patients are having bleeding episodes, regardless of platelet count. Standard first-line treatment for ITP in adults includes corticosteroids with intravenous immune globulin (IVIG) or anti-D immune globulin for patients who have significant risk for active bleeding.[4] Although the increase in platelet count after transfusion is often not optimal and patient response is transient, platelet transfusion may help patients with life-threatening bleeding achieve hemostasis.[6] Complete response rates after corticosteroid therapy range from 50% to 90%, but only 10-30% of patients achieve a durable remission after corticosteroids are tapered or discontinued.[4] Splenectomy has been shown to provide durable complete responses for two thirds of patients whose ITP does not respond to corticosteroids, with a median duration of follow-up of seven years.[7] In patients who do not achieve a durable complete response after splenectomy, ITP often becomes a chronic condition where the goal of treatment is to maintain a hemostatic platelet count while minimizing the toxicity associated with therapy.[5] Approximately 30-40% of patients do not respond to or relapse after splenectomy and have a degree of thrombocytopenia that requires therapy.[5] Corticosteroids and IVIG are the initial options for treating acute episodes of bleeding or severe thrombocytopenia in patients with refractory ITP. Long-term use of corticosteroids is limited by complications, including osteoporosis, cataracts, hyperlipidemia, and hyperglycemia.[5]

Options to manage chronic ITP refractory to splenectomy include rituximab, danazol, azathioprine, cyclophosphamide, cyclosporine, and accessory splenectomy.[8] Rituximab, a monoclonal antibody targeting CD20 antigen, depletes B cells that produce antiplatelet antibodies.[5] A complete response rate of 46% was observed in splenectomized and non-splenectomized patients receiving rituximab. The drug was generally well tolerated, with 18% of patients experiencing grade 1 or 2 infusion reactions.[9] Azathioprine, cyclosporine, and cyclophosphamide are used to suppress T-cell production or activation.[10,11,12,13] Cyclosporine use is limited by nephrotoxicity and headaches.[10] Azathioprine use may lead to hepatotoxicity and neutropenia, and cyclophosphamide may cause myelosuppression and infections.[11,12] Danazol impairs clearance of antibody-coated platelets; however, patients receiving danazol may experience weight gain, hirsutism, and liver dysfunction.[13] These agents are associated with complete response rates of 6-39% in patients with platelet counts of < 30 x 109 platelets/L and partial responses in up to 70% of patients.[8] Patients generally need to continue therapy with azathioprine and danazol to sustain a response. Oprelvekin (recombinant human interleukin 11) stimulates thrombopoiesis in patients with chemotherapy-induced thrombocytopenia.[14] However, when studied in patients with chronic ITP, no patients responded to oprelvekin treatment and significant toxicity was reported.[15]

Until recently, agents used to manage ITP have targeted immune-mediated platelet destruction. A new class of agents has been developed to target decreased platelet production in patients with chronic ITP. First-generation thrombopoietic agents included recombinant human thrombopoietin and nonglycosylated thrombopoietin.[16] The development of these entities halted after thrombopoietin autoantibodies were found in patients repeatedly treated with these drugs. These autoantibodies developed in both healthy volunteers and patients with cancer and led to severe, persistent thrombocytopenia.[17,18] Romiplostim and eltrombopag stimulate the thrombopoietin receptor and platelet production without inducing the production of autoantibodies.[16] Romiplostim, a subcutaneous injection, and eltrombopag, an oral small molecule, are second-generation thrombopoietic growth factors.[5] They bear no structural resemblance to endogenous thrombopoietin, thus minimizing patients' risk of developing thrombopoietin autoantibodies.[5,16]


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