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 tolerability 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.