ITP、TTP诊治新进展 PPT课件

Results of Bone Marrow Examinations in Patients with Chronic Immune Thrombocytopenic Purpura Treated with Eltrombopag
RAISE, REPEAT和EXTEND 应用Eltrombopag18个月并未出现临床相关骨髓异常或骨髓纤维化 James B. et al . Poster Session: Disorders of Platelet Number or Function poster 2435.
分组
复发率
Dex单药组 Dex联合Rituximab组 Dex+Rituximab抢救治疗组
23%(3/13) 23%(6/26) 14%(2/14)
30月RD率
需特异性抗 ITP治疗率
77%
33%
71%
29%
85%
36%
长期随访发现，与Dex单药组相比， Dex联合Rituximab组在长期不良反应、 复发率、有效时间和所需进一步特异性抗ITP治疗等方面无显著性差异
Roberto Stasi, et al. Poster Session: Disorders of Platelet Number or Function poster 1311.
Long-Term Treatment of Chronic Immune Thrombocytopenic Purpura with Oral Eltrombopag: Results From the EXTEND Study
Agents
对象：治疗前组6例，促血小板生成物治疗组12例(Nplate n=5， eltrombopag n=2，AKR-501 n=5)，对照组15例
结果：治疗前后Treg数目无显著变化，但是用药后Treg抑制功能 明显改善并伴随细胞群(如分泌IL-2的Th细胞降低，Th1细胞降低) 和细胞因子表达的改变(如sCD40L下降和TGF-b上升)
Francesco Zaja et al. Poster Session: Disorders of Platelet Number or Function poster 2415.
High-Dose IgG Alters the Relative Expression of Fcgamma RIIA and Fcgamma RIIB On Human Macrophages: A Mechanism for IVIG Therapy in Human Immune Thrombocytopenia
结论：促血小板生成物能够改善 ITP患者Treg功能
Weili Bao et al. Oral Session: Disorders of Platelet Number or Function poster 684.
Subcutaneous Injections of Low-Dose Anti-CD20 Veltuzumab for Treatment of Relapsed Immune Thrombocytopenia (ITP)
James B. Bussel, et al. Oral Session: Disorders of Platelet Number or Function 681.
Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenia (ITP) Treated with Romiplostim in Two
6.6%(128) 1.1%(21)
13.1%(51) 6.9%(27)
6.1%(61) 14.6%(11 2)
10.8%(35) 8.9% (68)
0.2%(2)
-
-
1.2% (9)
Romiplostim明显降低BREs发生率，减少丙球使用率，在切脾 及未切脾两组效果相似
Antoine 百度文库roissart et al. Poster Session: Disorders of Platelet Number or Function poster 891.
发生在低于最高plt值， 18%(3/17)发生在接近最高plt值时 结论：TEEs发生于Eltrombopag组，与治疗前无显著性差异，TEEs与
plt不存在相关
James B. et al . Poster Session: Disorders of Platelet Number or Function poster 2433.
Platelet Counts Following Eltrombopag Discontinuation in Patients with Chronic Immune Thrombocytopenic Purpura
TRA100773A，TRA100773B和RAISE 停用Eltrombopag后血小板减低和安慰剂组相似，plt 短暂
多中心、I/II期临床试验 对象：25例ITP患者（病史>6月、对一种或以上标准治疗无效、plt<50 x
109/L) 结果：62%起效(CR+PR+MR), 29%获得CR 结论：低剂量veltuzumab (2次, 间隔2w) 在复发性ITP疗效可，
与静脉注射相比，皮下注射更方便
Mansoor N. Saleh el al. Poster Session: Disorders of Platelet Number or Function poster 1322.
降低可能与停用ltrombopag无关，而是反映ITP患者plt波动，且plt 降低与出血无关
Xingmin Feng, et al. Poster Session: Disorders of Platelet Number or Function poster 3517.
Improved Regulatory T Cell Activity in Patients with Chronic Immune Thrombocytopenia Purpura Treated with Thrombopoietic
5% 8%
Romiplostim 显著降低未切脾ITP患者切脾率和治疗失败率，安全性 与标准治疗组相似
David J Kuter, et al. Oral Session: Disorders of Platelet Number or Function 679.
Long-Term Efficacy and Safety of Romiplostim for the Treatment of Patients with Chronic Immune Thrombocytopenia (ITP): 5-Year Update From an Open-Label Extension Study
与GPIIbIIIa相比，GPIb抗体介导的ITP患者对IVIG和激素治疗疗效 差
影响巨噬细胞FcgammaRIIA/FcgammaRIIB平衡可能是 IVIG 在ITP治疗中的机制之一
Salley Pels, et al. Oral Session: Disorders of Platelet Number or Function poster 683.
Relative Efficacy of Steroid Therapy in Ameliorating Autoimmune Thrombocytopenia Mediated by Anti-Platelet GPIIbIIIa Versus GPIbαAntibodies
结论：2年随访发现，口服Eltrombopag耐受性好，能够有效提升plt 数目、减少出血症状
Mansoor N. Saleh el al. Oral Session: Disorders of Platelet Number or Function 682.
Thromboembolic Events Observed in Eltrombopag Clinical Trials in Chronic Immune Thrombocytopenic Purpura
对象：299例患者，起始剂量50mg/d,调整剂量(25-75mg/d)， 使plt在 50-200x109/L
结果：86%患者plt≥50 x 109/L，切脾和未切脾患者效果相似(89%和 82%)
不良反应：83%出现轻到中度不良反应，最常见的是头痛(23%)、上 呼吸道感染(17%)、鼻咽炎(17%)、疲乏(13%)、关节痛(12%)、腹泻 (11%)等。此外肝功改变(8%)、血栓(4%)。86例骨髓活检(开始治疗1 年后)中未发现治疗相关改变。
Long Term Follow up Analysis Following Front Line Therapy with Dexamethasone or Dexamethasone Plus Rituximab in Adults
with Primary Immune Thrombocytopenia
Phase 3 Placebo-Controlled Clinical Trials
BREs 发生率
切脾 N=42
Romiplosti m
未切脾 N=42
5.4%(53) 7.8%(75)
应用丙球率 1.3%(13) 0.8%(8)
相关住院率
-
-
安慰剂组
总体 N=84
切脾 N=20
未切脾 N=21
总体 N=41
最常见不良事件：头痛(32%)、鼻咽炎(30%)、挫伤(28%)、疲 惫(28%) 等;
17例发生血栓( 6% )，随随访时间延长发生率并未增加；9例骨髓 网状蛋白增多，但未发展为纤维化；2例出现中和性抗体，停药后 消失;
结论：5年随访发现，应用Romiplostim长期治疗ITP能够维持 plt数目，剂量调节方便，耐受性好，不良事件发生率并未随时间 延长而增加;
Treatment and 6-Month Safety Follow-up
分组
Romiplostim 标准治疗组
切脾率
治疗失败率
严重不良 事件率
9% (14/157) 12%(18/157)
23%
36%（28/77） 30%（23/77）
37%
p<0.0001
p=0.0005
治疗相关严重 不良事件率
对象：成人未切脾ITP患者， Romiplostim组154例， SOC组70例，治疗52w
结果：与SOC组相比，Romiplostim组患者BREs发生 率下降67%（3.1% vs 9.4%)，应用免疫球蛋白率下降 95%（0.2% vs 4.8%）
结论：与SOC相比，Romiplostim能够显著降低 BREs发生率及应用免疫球蛋白率
Part I: ITP诊治新进展
Comparison of Splenectomy and Treatment Failure Incidence in Nonsplenectomized Patients with Immune Thrombocytopenia (ITP) Receiving Romiplostim or Medical Standard of Care: 1-Year
Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenic Purpura (ITP) Receiving Romiplostim or Medical Standard of Care
TRA100773A, TRA100773B, RAISE， REPEAT和EXTEND 治疗前TEEs(血栓事件)发生率为3.2%(16/493), 治疗后Eltrombopag组发
生率为3.8%(17/446),而安慰剂组无TEEs发生 最常见的TEEs是深静脉血栓(n=8)和肺动脉血栓(n=6)82%(14/17)的TEEs