咖啡酸片联合大剂量地塞米松治疗ITP的疗效和安全性研究

发布时间：2018-08-07 09:33

【摘要】：研究背景原发免疫性血小板减少症(primary immune thrombocytopenia,ITP)是一种常见的出血性疾病,约占出血性疾病的33%。ITP主要临床表现为皮肤、粘膜自发性出血,严重者可出现颅内出血,甚至危及生命。目前公认的ITP发病机制是患者对自身抗原耐受性的丢失,进而导致血小板破坏增加及/或巨核细胞成熟障碍。大剂量地塞米松(high-doesdexamethasone,HD-DXM)冲击治疗(40mg/天,连用4天,2星期为1个周期)是当前治疗ITP的一线方案。但是大剂量地塞米松治疗ITP患者的长期缓解率不高。咖啡酸(caffeic acid,CFA)具有抗氧化、提升白细胞数目、抗炎、提升血小板数目、止血等作用。我们的一项多中心临床研究发现,咖啡酸能够显著提高ITP患者的血小板数量,对ITP可能具有一定的治疗价值。ITP的发病机制具有多样化的特点,单药治疗ITP存在不足与风险。研究目的评价咖啡酸片联合大剂量地塞米松治疗新诊断ITP的疗效和安全性。研究方法本试验采用系统性回顾分析的研究方法。共收集就诊于山东大学齐鲁医院60名新诊断的ITP患者,其中A组包含34人,B组包括26人。A组患者接受了大剂量地塞米松1个周期或2个周期冲击治疗,同时口服咖啡酸片(0.9g/天,每天3次)12周。B组患者仅接受大剂量地塞米松1个周期或2个周期冲击治疗。主要研究患者的总反应率(overall response,OR)、完全反应率(complete response,CR)、治疗后各时间点(第7天、第14天、第21天、第28天、2个月、3个月、4个月、5个月、6个月)血小板数目、出血评分、起效时间(time to response,TTR)及药物不良反应。同时统计患者的性别、年龄、初始血小板数目等基本情况。结果(1)A组患者中位年龄为45(18～69)岁,男女比例为8/26,初始血小板中位数为4.5(0～27)×109/L;B组患者中位年龄49.5(27～67)岁,男女比例为9/17,初始血小板中位数是7(0～28)×109/L。两组患者的性别、年龄及初始血小板数目均无显著统计学差异(P值分别为:0.87、0.35、0.54)。(2)治疗28天后,A组总反应率是79.4%(27/34),完全反应率是58.8%(20/34);B组总反应率是57.7%(15/26),完全反应率是50%(13/26),两组总反应率及完全反应率的差异无显著统计学差异(P值分别为0.069、0.496)。(3)治疗后,两组各时间点(第7天、第14天、第21天、第28天、第2个月、第3个月、第4个月、第5个月、第6个月)血小板数目差异无统计学意义(P 值分别为:0.84、0.21、0.90、0.75、0.62、0.23、0.46、0.56、0.52)。各时间点(第7天、第14天、第21天、第28天、第2个月、第3个月、第4个月、第5个月、第6个月)血小板数目增值也无显著统计学差异(P值分别为:0.90、0.19、0.86、0.81、0.79、0.18、0.18、0.33、0.32)。(4)A组患者出血评分的降低值明显大于B组(P=0.019),即咖啡酸联合大剂量地塞米松组比大剂量地塞米松单药组更好的改善患者的出血症状。(5)A组中位起效时间是4.5(1～22)天,B组中位起效时间是6(2～57)天,无显著统计学差异(P=0.95)。(6)A组和B组的不良反应轻微,无需停药,均可自行缓解。结论咖啡酸片联合大剂量地塞米松治疗成人新诊断的ITP的总反应率为79.4%,具有良好的疗效,但与单药组相比无统计学差异。咖啡酸片联合大剂量地塞米松比单用大剂量地塞米松可以更好的改善患者的出血症状。两组患者各时间点的血小板计数相比均无显著统计学差异。两组的起效时间无显著统计学差异。咖啡酸片联合大剂量地塞米松治疗ITP与大剂量地塞米松单药组相比,不良反应没有叠加,耐受性良好。
[Abstract]:Background primary immuno thrombocytopenia (primary immune thrombocytopenia, ITP) is a common hemorrhagic disease. The main clinical manifestation of 33%.ITP in hemorrhagic disease is skin and spontaneous bleeding of mucous membrane. Severe patients can appear intracranial hemorrhage and even endanger life. The present pathogenesis of ITP is that the pathogenesis of ITP is the patient's resistance to itself. Loss of primary tolerance leads to increased platelet destruction and / or megakaryocyte maturation. Large dose high-doesdexamethasone (HD-DXM) impact therapy (40mg/ days, 4 days, 2 weeks for 1 cycles) is the first line of current treatment for ITP, but the long-term remission rate of ITP patients with large dose of dexamethasone is not high. Caffeic acid (CFA) has antioxidation, increases the number of leukocytes, increases the number of white blood cells, increases the number of platelets, and stops blood. Our multicenter clinical study has found that caffeic acid can significantly increase the number of platelets in ITP patients, and the pathogenesis of ITP, which may have a certain therapeutic value, is characterized by a variety of characteristics, single drug treatment. The purpose of this study was to evaluate the efficacy and safety of ITP with a large dose of dexamethasone combined with a large dose of dexamethasone in the treatment of a new ITP. A systematic retrospective analysis was used in this study. A total of 60 newly diagnosed ITP patients diagnosed in Qilu Hospital of Shandong University were collected, including 34 in group A, and 26 in B group.A. Group patients received 1 cycles or 2 cycles of shock treatment with large dose of dexamethasone, and oral caffeic acid tablets (0.9g/ days, 3 times per day) for 12 weeks of group.B patients received only 1 cycles or 2 cycles of severe dexamethasone. The total response rate (overall response, OR), the total response rate (complete response, CR), and the cure rate (complete response, CR) were studied. Each time point (seventh days, fourteenth days, twenty-first days, twenty-eighth days, 2 months, 3 months, 4 months, 5 months, 6 months) the number of platelets, bleeding score, time to response, TTR and adverse drug reactions. Meanwhile, statistics of sex, age, and initial platelet count in patients (1) the median age of patients in group A was 45 (18~69) years. The proportion of men and women was 8/26, the median of the initial platelets was 4.5 (0~27) x 109/L; the median age of the B group was 49.5 (27~67) years and the male and female ratio was 9/17. The median of the initial platelets was 7 (0~28) x 109/L. two, and there was no significant difference between the age and the initial platelets (P value, 0.87,0.35,0.54). (2) after 28 days, A The total reaction rate was 79.4% (27/34), the total reaction rate was 58.8% (20/34), the total reaction rate in the B group was 57.7% (15/26), the total reaction rate was 50% (13/26). There was no significant difference between the two groups of total reaction rate and complete reaction rate (P value 0.069,0.496 respectively). (3) after treatment, the two groups of time points (seventh days, fourteenth days, twenty-first days, twenty-eighth days, second months,) There was no significant difference in the number of platelets in third months, fourth months, fifth months and sixth months (P value was 0.84,0.21,0.90,0.75,0.62,0.23,0.46,0.56,0.52). There was no significant difference in the number of platelets at all time points (seventh days, fourteenth days, twenty-first days, twenty-eighth days, second months, third months, fourth months, fifth, sixth months) (P The value of 0.90,0.19,0.86,0.81,0.79,0.18,0.18,0.33,0.32). (4) the decrease value of bleeding score in group A was significantly greater than that of group B (P=0.019), that is, caffeic acid combined with large dose dexamethasone group was better than the large dose of dexamethasone single drug group to improve the patient's bleeding symptoms. (5) the onset time of the A group was 4.5 (1~22) days, and the middle effect time of group B was at the middle level. 6 (2~57) days, no significant statistical difference (P=0.95). (6) the adverse reaction of group A and group B was mild, no need to stop drugs, and it could be relieved. Conclusion the total reaction rate of caffeic acid tablets combined with large dose of dexamethasone in the treatment of adult newly diagnosed ITP has good effect, but there is no statistical difference compared with that of the single drug group. There was no significant difference in the platelet count at all time points between the two groups. There was no significant difference in the onset time between the two groups. There was no significant difference in the onset time between the two groups. The combination of the caffeic acid tablets combined with the large dose of dexamethasone was compared with the large dose of the dexamethasone group. The adverse reactions were not superimposed and well tolerated.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R558.2

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