Evaluation of bleeding and thrombotic events during long‐term use of romiplostim in patients with chronic immune thrombocytopenia (ITP)

Abstract

thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP). J Thromb Haemost 2010; 8: 1372-82.Summary. Background: Romiplostim is a peptibody protein that raises platelet counts during long-term treatment of patients with chronic immune thrombocytopenia (ITP). Clinical outcomes related to increased platelet counts include a reduced risk of bleeding and a potential risk of thrombosis. Objective: To evaluate bleeding and thrombotic events occurring in chronic ITP patients during two phase 3, randomized, placebo-controlled, 24-week studies of romiplostim and during subsequent treatment in an open-label extension study. Patients/Methods: In the phase 3 trials, 125 patients were randomized to romiplostim or placebo; romiplostim dose was adjusted to maintain platelet counts of 50-200 · 10 9 L )1. Patients who completed the phase 3 trials could enroll in the extension study in which all patients received romiplostim. Results: In the phase 3 trials, a significantly greater percentage of patients treated with placebo (34%) had bleeding adverse events of moderate or greater severity than did patients treated with romiplostim (15%, P = 0.018). In the extension study, the incidence of bleeding adverse events of moderate or greater severity decreased from 23% of patients in the first 24 weeks to 12% after 24-48 weeks, remaining £ 6% thereafter. The exposure-adjusted incidence of thrombotic events was 0.1 per 100 patient-weeks in the phase 3 studies, and 0.08 per 100 patient-weeks in the extension study where patients received romiplostim for up to 144 additional weeks. Conclusions: The incidence and severity of bleeding was decreased in chronic ITP patients treated with romiplostim compared with placebo, and the incidence of thrombotic events was not different between the two groups.

Splenectomy as a curative treatment for immune thrombocytopenia: a retrospective analysis of 233 patients with a minimum follow up of 10 years

“…However, splenectomy did not seem to increase the rate of thrombotic complications, compared to medical treatments. [25][26][27][28][29][30] Overall, complications were less frequent than in previously reported cohorts, which were fatal in a minority of the cases and mainly affected non-responding patients. 27,29 It is likely that the low incidence of complications in our series was due to the early adoption of splenectomy (median time from diagnosis to surgery 13 months), which meant major pre-splenectomy toxicities were avoided and which was probably justified by the fact that rituximab and TPO-ra were not yet available.…”

Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate

“…Very few patients receiving long-term romiplostim treatment discontinue the drug because of adverse events [34,43]. There was no evidence of increased risk of thromboembolic events [34,45] and no evidence of antibodies that cross-reacted with endogenous TPO or affected the platelet response [34,43], except in one instance, where a patient transiently developed romiplostim-neutralizing antibodies. In two patients neutralizing antibodies to romiplostim were detected which did not cross-react with endogenous TPO.…”

A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy

“…40,41 Most thromboembolic events have been observed in patients with at least 1 additional risk factor for thrombosis, such as comorbidities, splenectomy, hospitalization, long-term steroid therapy, or previous history of vascular disease. 36,38,39,42 Pregnant women are subject to thrombosis because of their hypercoagulable state. Therefore, thrombosis is 1 of the major issues in the management of ITP in pregnancy with such agents.…”