Determining Optimum Medical Therapy for ITP

描述(申请人提供)：患有免疫性血小板减少症(ITP)的成年人通常最初使用类固醇治疗。然而，绝大多数人要么没有改善，要么没有持久的回应。当类固醇逐渐减少或停止时，血小板计数会下降，因此，大多数患者需要进一步治疗才能维持止血血小板计数。然而，目前对于服用类固醇后的最佳选择还没有达成共识。目前的选择包括医疗选择，更多的大剂量类固醇，利妥昔单抗(Ritux)或促血小板生成剂(TPO试剂)；或外科选择，脾切除术。泼尼松在第二个疗程后对极少数患者有持久影响；在单臂研究中被吹捧为有疗效的大剂量地塞米松(Dex)，在最近的一项对比试验中只有17%的患者有持久效果。抗CD20抗体(利妥昔单抗，Ritux)最初对50%的ITP患者有效，但治疗3年后，似乎只有20%的成年人保持了令人满意的血小板计数。与标准/安慰剂相比，TPO制剂刺激骨髓血小板生成，多项研究证明其疗效。这些药物显然提供了一种有用的治疗方法，但价格昂贵，长期效果尚不清楚，而且人们认为这种治疗永远不会被取消。由于脾切除是不可逆转的，具有已知的医学后果，而且大多数患者不希望接受脾切除，我们已经探索了可能提供令人满意的替代方案的医疗选择的组合。我们发现，在最近的一项先导性研究中，在接受治疗的患者中，有一半的患者联合使用美罗华和地塞米松(地塞米松)可导致一年或一年以上的完全缓解。与人们的看法相反，TPO制剂似乎在某些情况下导致持续的止血血小板计数，可能是通过诱导调节性T细胞(Tregs)。因此，总体而言，这项拟议的规划赠款的目标是为 一项临床试验比较了地塞米松、抗CD20和TPO制剂的组合，以了解哪一种手臂可以导致更多的患者，从最初的治疗起3年内持续有效。正如2009年9月由美国国立卫生研究院主办的科学状况会议上指出的那样，迫切需要对当前最好的医疗疗法进行比较。我们在这份U34拨款中建议，通过让指导委员会就研究方案达成共识，并与U24资源小组建立联系，以获得统计输入，实施IRB和IND，设计病例报告表格和其他材料，如程序手册，并积累成功完成研究所需的场地，为多中心研究做准备。

DESCRIPTION (provided by applicant): Adults with Immune Thrombocytopenia (ITP) are usually treated initially with steroids. However, the great majority either do not improve or do no have a lasting response. The platelet count falls as the steroids are tapered or stopped and as a result, most patients require further therapy to maintain a hemostatic platelet count. However, there is no current consensus about the best option following steroids. The current choices consist of the medical options, more high dose steroids, rituximab (ritux), or thrombopoietic agents (TPO agents); or the surgical option, splenectomy. Prednisone leads to lasting effects in very few patients following a second course; high dose dexamethasone (dex), touted in single arm studies to have curative effects, had lasting effects in only 17% of patients in a recent comparative trial. Anti-CD20 (Rituximab, ritux) leads to initial benefit in 50% of ITP patients but3 years after treatment, it appears that only 20% of adults sustain satisfactory platelet counts. TPO agents stimulate bone marrow platelet production and multiple studies demonstrate efficacy as compared to standard /placebo. These agents clearly provide a useful therapy, but are expensive, have still unclear long-term effects, and it is believed that this treatment can never be withdrawn. As removal of the spleen is irreversible, has known medical consequences, and most patients do not wish to undergo splenectomy, we have explored combinations of medical options that may offer satisfactory alternatives. We have found that ritux in combination with dexamethasone (dex) resulted in complete remissions for one or more years in half of the patients treated in a recent pilot study. Contrary to belief, TPO agents appear to lead a sustained off treatment hemostatic platelet count in some cases, possibly via the induction of regulatory T cells (Tregs). Thus overall the goal of this proposed planning grant is to prepare for a clinical trial comparing the combination of dex with anti- CD20 to a TPO agent to see which arm leads to more patients with a lasting effect at 3 years from initial treatment. As pointed out at the NIH-sponsored State of the Science meeting in September 2009, a comparison of the best current medical therapies is urgently needed. We propose in this U34 grant to prepare for a multicenter study by having the Steering Committee form a consensus on the study protocol and interface with the U24 Resource group to gain statistical input, implement an IRB and IND, and design case report forms and other material such as a manual of procedures and to accrue the sites required to successfully complete the study.