Background: Immune thrombocytopenic purpura (ITP) is characterized by platelet deficiency due to platelet destruction and/or inadequate production. Initial therapy consists of corticosteroids or intravenous immunoglobulin (IVIg). Patients with chronic refractory disease might undergo splenectomy. Although there is no treatment of choice in those who do not respond to splenectomy, immunosuppressive agents are typically prescribed. Romiplostim is the first available drug in a recently developed class of agents that work through stimulation of the thrombopoietin (TPO) receptor (c-Mpl) to increase platelet production.
Objective: The aim of this report was to review the mechanism of action, pharmacology, clinical activity, and adverse events associated with the use of romiplostim for the treatment of thrombocytopenia in patients with chronic ITP.
Methods: MEDLINE, Google Scholar, International Pharmaceutical Abstracts, and Web of Science were searched for English-only clinical trials and reviews (publication dates: 2000-June 1, 2009; key terms: romiplostim, Nplate, ITP, and idiopathic and immune thrombocytopenic purpura). Abstracts from the 2000-2008 meetings of the American Society of Hematology and references from relevant articles were reviewed.
Results: A total of 6 studies were included. Romiplostim is the first marketed agent developed to directly stimulate the bone marrow to produce platelets. Produced in Escherichia coli using recombinant DNA technology, it is an Fc-peptide fusion protein. It works intracellularly in a manner similar to that of the naturally occurring TPO to activate the transcriptional pathways, leading to increased platelet production via stimulation of the c-Mpl receptor. Romiplostim was approved by the US Food and Drug Administration for the treatment of chronic ITP primarily based on the findings from 2 multicenter, randomized, placebo-controlled, parallel-group studies in 125 adult patients with chronic ITP and an insufficient response to corticosteroids, IVIg, and/or splenectomy. The most common prior treatments were corticosteroids (94%) and IVIg (80%). Sixty-three patients (50%) were splenectomized a median of 6.6 years earlier. Baseline platelet counts were <30 x 10(9) cells/L. The initial dose of romiplostim was 1 microg/kg/wk SC, with adjustments to maintain platelet counts between 50 and 200 x 10(9) cells/L. The primary end point was a durable platelet response (>or=50 x 10(9) cells/L for >or=6 of the last 8 weeks of treatment). The proportion of patients in whom a durable platelet response was achieved was significantly greater with romiplostim than with placebo (49% vs 2%, respectively; P < 0.001). Overall platelet responses (durable plus transient) were achieved in 83% (69/83) with romiplostim and 7% (3/42) with placebo (P < 0.001). An interim report of findings from an ongoing extension study found that response was maintained for up to 156 weeks (median, 69 weeks) with romiplostim. The most common adverse events were headache (37%), nasopharyngitis (32%), contusion (30%), epistaxis (30%), fatigue (30%), arthralgia (25%), and diarrhea (25%).
Conclusions: Based on the findings from this review, romiplostim administration has been associated with a durable platelet response in these patients with refractory chronic ITP. Romiplostim has been found to be generally well tolerated.