, Volume 72, Issue 3, pp 415-435
Date: 12 Dec 2012


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Romiplostim (Nplate®) is an Fc-peptide fusion protein (peptibody) that acts as a thrombopoietin receptor agonist; it has no amino acid sequence homology with endogenous thrombopoietin. This article reviews the clinical efficacy and toler-ability of subcutaneous romiplostim in adults with immune thrombocytopenia (ITP), as well as summarizing its pharmacological properties.

The efficacy of 12 or 24 weeks’ therapy with subcutaneous romiplostim was compared with that of placebo in patients with ITP in three randomized, double-blind, multicentre, phase III trials. In the two 24-week trials, the durable platelet response rate (primary endpoint) was significantly higher with romiplostim than with placebo in both splenectomized and nonsplenectomized patients. In addition, the majority of romiplostim recipients were able to discontinue or reduce their concurrent ITP therapy, and romiplostim improved health-related quality of life (HR-QOL). In the 12-week trial in splenectomized or nonsplenectomized Japanese patients with ITP, the median number of weeks with a platelet response (primary endpoint) was significantly higher with romiplostim than with placebo. Two extension studies (with median durations of romiplostim treatment of 78 and 100 weeks) demonstrated that long-term therapy with romiplostim maintained platelet counts in the target range in patients with ITP.

In a randomized, open-label, multicentre, 52-week, phase IIIb trial, romiplostim was more effective than the medical standard of care in nonsplenectomized patients with ITP who had received at least one prior ITP treatment. Significantly fewer patients receiving romiplostim versus the medical standard of care experienced treatment failure or required splenectomy (co-primary endpoints), and clinically meaningful improvements from baseline in HR-QOL scores were seen with romiplostim.

Subcutaneous romiplostim was generally well tolerated in patients with ITP; in short-term trials, the majority of adverse events were of mild to moderate severity and appeared to be related to the underlying thrombocytopenia. The incidence of bleeding events of at least grade 3 severity did not significantly differ between romiplostim and placebo recipients, and was significantly lower with romiplostim than with the medical standard of care. Romiplostim did not appear to be associated with an increased risk of haematological malignancies or an increased risk of thrombotic events. Although binding antibodies against romiplostim or thrombopoietin developed in some romiplostim recipients, with neutralizing antibodies to romiplostim detected in two romiplostim recipients, antibodies cross reacting to thrombopoietin have not been detected. Romiplostim was associated with modest increases in bone marrow reticulin in some patients with ITP; reductions in reticulin were usually seen when romiplostim was discontinued.

In conclusion, subcutaneous romiplostim is a valuable agent for use in patients with refractory chronic ITP.

Various sections of the manuscript reviewed by: D.M. Arnold, Department of Medicine, McMaster University, Hamilton, ON, Canada; P.H. Bolton-Maggs, Department of Clinical Haematology, Manchester Royal Infirmary, Manchester, UK; A. Janssens, Department of Hematology, University Hospitals Leuven, Leuven, Belgium; M. Khellaf, Department of Internal Medicine, CHU Henri-Mondor, Creteil, France.
Data Selection
Sources: Medical literature (including published and unpublished data) on romiplostim was identified by searching databases (including MEDLINE, EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE and EMBASE search terms were ‘romiplostim’ and (‘immune thrombocytopenic purpura’ or ‘idiopathic thrombocytopenic purpura’ or ‘purpura, thrombocytopenic, idiopathic’). Searches were last updated 23 January 2012.
Selection: Studies in patients with immune thrombocytopenia who received romiplostim. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Romiplostim, immune thrombocytopenia, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.