ITP中国专家共课件.ppt

* * * * * * * * * * * * * * 两种统计方式均表明治疗组疗效显著高于对照组. * * * * * EXPLANATORY TEXT eltrombopag (SB 497115) is a novel, first in class, oral small molecule platelet growth factor In preclinical and clinical studies eltrombopag has been shown to stimulate megakaryocyte differentiation and proliferation and increases platelet counts in chimpanzees and humans in a dose dependent manner. As a small molecule, eltrombopag has lower immunogenic potential, an issue for peptidyl drugs. Ex vivo experiments with human platelets and in vivo studies in healthy volunteer studies have demonstrated that eltrombopag does not prime platelets for activation and does not adversely affect platelet function. * Eltrombopag interacts with the Tpo-R differently to endogenous Tpo, with the transmembrane region of the receptor important for the activity of the compound. Eltrombopag binding to the Tpo-R leads to signal transduction via the JAK-STAT pathway, resulting in proliferation and differentiation of cells in the megakaryocyte lineage and increased platelet production. * Adults with chronic ITP who had a platelet count 30,000/μL and ≥1 prior ITP therapy were eligible for RAISE. These patients were randomized 2:1 (eltrombopag:placebo) and stratified by splenectomy status, concomitant maintenance ITP therapy, baseline platelet count ≤15,000/μL. Safety assessments, bleeding, and platelet counts were monitored at weekly visits during the first 6 weeks of the study, and at visits every 4 weeks thereafter. Post-therapy visits were scheduled for 1, 2, and 4 weeks following discontinuation or completion of the study After Day 22, the dose of eltrombopag could be increased to 75 mg once daily or decreased to 25 mg once daily or less often based on each patient’s platelet response; after 6 weeks of treatment patients could reduce their concomitant ITP medication. Any change in eltrombopag or concomitant ITP medication dose resulted in weekly visits during the subsequent 4 weeks. * * * Patient