PF699 LUSUTROMBOPAG IS A SAFE TREATMENT OPTION FOR THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC LIVER DISEASE UNDERGOING A SCHEDULED INVASIVE PROCEDURE: POOLED SAFETY ANALYSIS FROM 3 STUDIES

Abstract

Background:Lusutrombopag is a thrombopoietin receptor agonist approved in Japan and US for improvement of thrombocytopenia, and in EU for severe thrombocytopenia, associated with chronic liver disease in patients undergoing planned invasive procedures. In an integrated analysis of 2 Phase 3 studies, lusutrombopag reduced the need for platelet transfusions compared to placebo.Aims:Treatment with thrombopoietin receptor agonists has been associated with an increased risk of thrombotic events in patients with chronic liver disease. Thus, a thorough safety assessment of new agents is critical. A pooled retrospective analysis of 3 clinical studies was performed to assess safety of lusutrombopag.Methods:Safety data from 3 double‐blind, randomized, placebo‐controlled studies in patients with chronic liver disease and thrombocytopenia undergoing a scheduled invasive procedure (Phase 2b: M0626 [Japan; JapicCTI‐121944], Phase 3: L‐PLUS 1 [Japan; JapicCTI‐132323] and L‐PLUS 2 [global; NCT02389621]) were pooled. Adults with platelet counts <50x109/L at baseline received lusutrombopag 3 mg or placebo for up to 7 days before a procedure scheduled 9–14 days after randomization. Platelet transfusion was given if the platelet count remained <50x109/L no more than 2 days prior to procedure. Adverse event data were collected from signing of informed consent until the end of the post‐treatment period or early termination.Results:The pooled safety population included 341 patients (n = 171, lusutrombopag; n = 170 placebo). Approximately 65% of patients in the lusutrombopag and placebo groups experienced an adverse event (Table). Thrombotic and thromboembolic adverse events occurred in 1.8% (3/171) of lusutrombopag patients (cardiac ventricular thrombosis, n = 1 [patient had prior history of cardiac ventricular thrombosis]; portal vein thrombosis, n = 2) and 2.4% (4/170) of placebo patients (mesenteric vein thrombosis, n = 2; portal vein thrombosis, n = 2). Overall, bleeding‐related adverse events occurred in less lusutrombopag vs placebo patients (15 [8.8%] vs 27 [15.9%]), respectively. The 3 adverse events leading to death were not considered treatment‐related but due to the progression of underlying disease.Summary/Conclusion:In this pooled safety analysis, lusutrombopag was safe and well‐tolerated in patients with thrombocytopenia and chronic liver disease undergoing invasive procedures. Approximately 50% fewer bleeding‐related adverse events and no increased risk of thrombotic and thromboembolic adverse events were observed in patients treated with lusutrombopag vs placebo.image