Romiplostim: a review of its use in immune thrombocytopenia.
ABSTRACT 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.
Article: Thrombocytopenia[Show abstract] [Hide abstract]
ABSTRACT: Thrombocytopenia means low platelet count. This is the most frequent cause of bleeding abnormalities. Petechias, purpuras, mucosal bleeding are typical clinical findings. Severe, even life threatening gastrointestinal or intracranial bleeding may also occur. Diagnostic laboratory finding is the prolonged bleeding time. There are several causes of thrombocytopenia. The major mechanisms for a reduced platelet count are decreased production and increased destruction of platelets, or both. The major task is to reveal the underlying cause. Examination of the bone marrow and the peripheral blood smear can be helpful as well as special diagnostics of the assumed disease. Therapy targets the underlying disease, and also involves platelet transfusion. However, in case of diseases with increased platelet activation and consumption, platelet transfusion is forbidden because it may lead to aggravation of the pathologic process. Orv. Hetil., 2014, 155(8), 291-303.Orvosi Hetilap 02/2014; 155(8):291-303. DOI:10.1556/OH.2014.29822
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ABSTRACT: Thrombopoietin-receptor agonists (TPOra) are the only treatments for immune thrombocytopenia (ITP) for which evidence of efficacy and safety from randomized, placebo-controlled trials is available. We sought to determine the long-term tolerability of the TPOra romiplostim, with a particular focus on thrombosis, bleeding, bone marrow reticulin, neoplasms/haematological malignancies and fatal events. Data from 13 romiplostim clinical trials in which 653 ITP patients received romiplostim for up to 5 years (921.5 patient-years) were pooled; subject incidence rates and exposure adjusted event rates (per 100 patient-years) were calculated. The rate of thrombotic events (6% of patients; 7.5 events/100 patient-years) did not appear to increase over time; 7 events were associated with platelet counts >400 x 10(9) /L and 10 with romiplostim doses exceeding current recommendations. Serious and grade ≥3 bleeding each occurred in approximately 8% of patients (~11 events/100 patient-years). Adverse events of bone marrow reticulin were recorded for 12 patients (1.8%; 1.3 events/100 patient-years; confirmed by bone biopsy in 10 patients), and bone marrow collagen for 1 patient (0.2%; 0.1 events/100 patient-years; confirmed by trichrome staining). Neoplasms and haematological malignancies occurred in 2.1% and 0.8% of patients, respectively (2.2 and 0.7 events/100 patient-years). Fatal events occurred in 3.7% of patients (2.6 events/100 patient-years; 4 events treatment-related). Romiplostim is the TPOra for which the longest duration of safety data is available. Our data demonstrate that long-term romiplostim treatment is well tolerated, with no new safety signals, even in patients treated for up to 5 years. This article is protected by copyright. All rights reserved.European Journal Of Haematology 08/2013; DOI:10.1111/ejh.12181 · 2.41 Impact Factor