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艾曲泊帕在成人原发免疫性血小板减少症中的治疗进展
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Abstract:
原发免疫性血小板减少症(ITP)是以孤立性外周血血小板计数减少为主要特点的一种自身免疫性疾病，患者出血风险高，严重影响患者生存质量，且该病暂无根治的治疗方法，故ITP的治疗应以提高血小板计数为目标，从而减少出血风险，减少与治疗相关的不良事件。目前成人原发性血小板减少的治疗取得了一定进展，其中艾曲泊帕作为第二代血小板生成素受体激动剂(TPO-RAs)是一种可靠的二线免疫性血小板减少症(ITP)治疗药物，不仅协同TPO生成血小板，还可增强造血干细胞增殖，另外还具有调节免疫功能，为了更有效地治疗ITP患者，目前有许多研究提出了艾曲泊帕联合其他用药的新攻略，本文就艾曲泊帕在成人ITP的治疗中的进展作一综述。
Primary Immune thrombocytopenia (ITP) is a prevalent autoimmune disorder characterized by isolated thrombocytopenia. Patients with ITP are at high risk for bleeding events, which severely affect the long-term survival of patients. There is no curative treatment available to date, so ITP treatment should aim at raising the platelet count, thereby reducing bleeding and other treat-ment-related adverse events. Currently, progress has been made in improving the treatment of adult ITP. The second-generation thrombopoietin receptor agonist eltrombopag is approved for second-line use in ITP, which synergizes with TPO to generate platelet, enhances proliferation of hematopoietic stem cells and regulates immune functions. Therefore, numerous studies have pro-posed a novel therapeutic strategy to effectively treat ITP through combined use of eltrombopag with other drugs. Here, we review the research progress of eltrombopag toward the treatment of ITP.
| [1] | Neunert, C., Terrell, D., Arnold, D., et al. (2019) American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia. Blood Advances, 3, 3829-3866. https://doi.org/10.1182/bloodadvances.2019000966 |
| [2] | 任丹薇, 刘文君. 巨核细胞发育和血小板生成的调控[J]. 中国实验血液学杂志, 2018, 26(6): 1876-1880. |
| [3] | Gudbrandsdottir, S., Ghanima, W., Nielsen, C., et al. (2017) Effect of Thrombopoietin-Receptor Ago-nists on Circulating Cytokine and Chemokine Levels in Patients with Primary Immune Thrombocytopenia (ITP). Platelets, 28, 478-483.
https://doi.org/10.1080/09537104.2016.1235691 |
| [4] | Sunohara, M., Sato, I. and Morikawa, S. (2017) Promoter Motifs Required for c-mpl Gene Expression Induced by Thrombopoietin in CMK Cells. Cellular and Molecular Biology, 63, 119-123.
https://doi.org/10.14715/cmb/2017.63.11.21 |
| [5] | Kao, Y.R., Chen, J.H., Narayanagari, S., et al. (2018) Thrombo-poietin Receptor-Independent Stimulation of Hematopoietic Stem Cells by Eltrombopag. Science Translational Medicine, 10, eaas9563.
https://doi.org/10.1126/scitranslmed.aas9563 |
| [6] | Vishnu, P. and Aboulafia, D. (2016) Long-Term Safety and Ef-ficacy of Romiplostim for Treatment of Immune Thrombocytopenia. Journal of Blood Medicine, 7, 99-106. https://doi.org/10.2147/JBM.S80646 |
| [7] | Gómez-Almaguer, D. (2018) Eltrombopag-Based Combination Treat-ment for Immune Thrombocytopenia. Therapeutic Advances in Hematology, 9, 309-317. https://doi.org/10.1177/2040620718798798 |
| [8] | Bussel, J., Kulasekararaj, A., Cooper, N., et al. (2019) Mecha-nisms and Therapeutic Prospects of Thrombopoietin Receptor Agonists. Seminars in Hematology, 56, 262-278. https://doi.org/10.1053/j.seminhematol.2019.09.001 |
| [9] | 杨默, 邱明慧. 血小板生成素的发现及应用[J]. 中国小儿血液与肿瘤杂志, 2018, 23(4): 217-219. |
| [10] | 刘建新, 江滨. 艾曲波帕在血小板减少中的临床应用[J]. 中国实用内科杂志, 2019, 39(8): 724-727. |
| [11] | 胡星月, 赵彤, 张思源, 乐丽霞, 宋朋飞, 李洁. 联合用药治疗成人原发免疫性血小板减少症[J]. 中国医药科学, 2023, 13(14): 45-48, 85. |
| [12] | Ashok, R. (2017) Immune Thrombocyto-penia: Pathogenesis and Treatment Approaches. Journal of Hematology & Transfusion, 5, Article 1056. |
| [13] | Erickson-Miller, C., DeLorme, E., Tian, S., et al. (2005) Discovery and Characterization of a Selective, Non-peptidyl Thrombopoietin Receptor Agonist. Experimental Hematology, 33, 85-93.
https://doi.org/10.1016/j.exphem.2004.09.006 |
| [14] | Di Paola, A., Palumbo, G., Tortora, C., et al. (2022) Eltrom-bopag in Paediatric Immune Thrombocytopenia: Iron Metabolism Modulation in Mesenchymal Stromal Cells. British Journal of Haematology, 197, 110-119.
https://doi.org/10.1111/bjh.18012 |
| [15] | U.S. Food and Drug Administration (2015) FDA Extends Use of Promacta in Young Children with Rare Blood Disorder. https://www.fda.gov/news-events/fda-newsroom/press-announcements |
| [16] | Cheng, G. (2012) Eltrom-bopag, a Thrombopoietinreceptor Agonist in the Treatment of Adult Chronic Immune Thrombocytopenia: A Review of the Efficacy and Safety Profile. Therapeutic Advances in Hematology, 3, 155-164.
https://doi.org/10.1177/2040620712442525 |
| [17] | Kim, T., Despotovic, J. and Lambert, M. (2018) Eltrombopag for Use in Children with Immune Thrombocytopenia. Blood Advances, 2, 454-461. https://doi.org/10.1182/bloodadvances.2017010660 |
| [18] | 刘锋, 房洪英, 谢冉, 等. 儿童原发性免疫性血小板减少症的二线治疗药物新选择: 艾曲波帕与罗米司亭[J]. 儿科药学杂志, 2023, 29(11): 56-60. |
| [19] | Young, J., Fan, X., Groarke, E., et al. (2022) Long-Term Eltrombopag for Bone Marrow Failure Depletes Iron. American Journal of Hematology, 97, 791-801. https://doi.org/10.1002/ajh.26543 |
| [20] | Ghanima, W., Godeau, B., Cines, D. and Bussel, J.B. (2012) How I Treat Immune Thrombocytopenia: The Choice between Splenectomy or a Medical Therapy as a Sec-ond-Line Treatment. Blood, 120, 960-969.
https://doi.org/10.1182/blood-2011-12-309153 |
| [21] | Yang, R., Li, J., Jin, J., et al. (2017) Multicentre, Randomised Phase III Study of the Efficacy and Safety of Eltrombopag in Chinese Patients with Chronic Immune Thrombocytopenia. British Journal of Haematology, 76, 101-110.
https://doi.org/10.1111/bjh.14380 |
| [22] | 孙慧平, 范青叶, 游建华, 等. 艾曲泊帕长期治疗成人慢性免疫性血小板减少症的疗效和安全性[J]. 临床血液学杂志, 2020, 33(1): 39-43. |
| [23] | Boyers, D., Jia, X., Crowther, M., et al. (2011) Eltrombopag for the Treatment of Chronic Idiopathic Thrombo-Cyto- penic Purpura. New England Journal of Medicine, 357, 2237-2247. |
| [24] | Grainger, J., Locatelli, F., Chots, T., et al. (2015) Eltrombopag for Children with Chronic Immune Thrombocy-Topenia (PETIT2): A Randomised, Multicentre, Placebo-Controlled Trial. Lancet, 2, e315-e325. |
| [25] | Iino, M., Sakamoto, Y. and Sato, T. (2020) Treatment-Free Remission after Thrombopoietin Receptor Agonist Discontinuation in Patients with Newly Diagnosed Immune Thrombocytopenia: An Observational Retrospective Analysis in Real-World Clinical Practice. International Journal of Hematology, 112, 159-168.
https://doi.org/10.1007/s12185-020-02893-y |
| [26] | Wong, R., Saleh, M., Khelif, A., et al. (2017) Safety and Effica-cy of Long-Term Treatment of Chronic/Persistent ITP with Eltrombopag: Final Results of the EXTEND Study. Blood, 130, 2527-2536.
https://doi.org/10.1182/blood-2017-04-748707 |
| [27] | 张紫婵, 毛琳, 周鹭. 艾曲波帕在血小板减少症中的治疗进展[J]. 交通医学, 2023, 37(2): 142-145. |
| [28] | Bolton-Maggs, P. and George, J. (2021) Immune Thrombocytopenia Treatment. New England Journal of Medicine, 385, 948-950. https://doi.org/10.1056/NEJMe2110953 |
| [29] | 张义霞, 蔡亚云, 周敏. 艾曲波帕联合激素治疗成人原发免疫性血小板减少症有效性及安全性分析[J]. 世界复合医学, 2022, 8(2): 22-25, 30. |
| [30] | 杜桂贤. 艾曲波帕与大剂量地塞米松治疗原发免疫性血小板减少症患者的临床疗效及安全性评价[J]. 甘肃科技, 2023, 39(2): 132-134. |
| [31] | Gómez-Almaguer, D., Herrera-Rojas, M., Jaime-Pérez, J., et al. (2014) Eltrombopag and High-Dose Dexamethasone as Frontline Treatment of Newly Diagnosed Immune Thrombo-cytopenia in Adults. Blood, 123, 3906-3908.
https://doi.org/10.1182/blood-2014-01-549360 |
| [32] | 汤虎成. 艾曲波帕联合大剂量地塞米松治疗原发免疫性血小板减少症的效果及安全性分析[J]. 当代医药论丛, 2021, 19(6): 105-106. |
| [33] | 洪攀, 傅佳萍, 封蔚莹, 等. 艾曲泊帕联合大剂量地塞米松治疗ITP疗效分析[J]. 浙江临床医学, 2020, 22(7): 1025-1027. |
| [34] | Zhang, L.Q., Zhang, M.J., Du, X., et al. (2020) Safety and Efficacy of Eltrombopag plus Pulsed Dexamethasone as First-Line Therapy for Immune Thrombocytopenia. British Journal of Haematology, 189, 369-378.
https://doi.org/10.1111/bjh.16327 |
| [35] | Liu, X.G., Hou, Y. and Hou, M. (2023) How We Treat Primary Immune Thrombocytopenia in Adults. Journal of Hematology & Oncology, 16, Article No. 4. https://doi.org/10.1186/s13045-023-01401-z |
| [36] | Lucchini, E., Zaja, F. and Bussel, J. (2019) Rituximab in the Treatment of Immune Thrombocytopenia: What Is the Role of This Agent in 2019? Haematologica, 104, 1124-1135. https://doi.org/10.3324/haematol.2019.218883 |
| [37] | 樊凤娇, 何继祥, 黄月婷, 等. 小剂量利妥昔单抗联合艾曲波帕治疗激素无效/复发成人原发免疫性血小板减少症的临床观察[J]. 临床内科杂志, 2021, 38(11): 773-775. |
| [38] | 白浩成, 冯静, 袁忠涛, 等. 小剂量利妥昔单抗联合艾曲波帕治疗激素耐药性ITP的临床疗效[J]. 西部医学, 2020, 32(1): 121-124. |
| [39] | Gómez-Almaguer, D., Colugna-Pedraza, P., Gómez-De, L., et al. (2019) Eltrombopag, Lowdose Rituximab, and Dexamethasone Combination as Frontline Treatment of Newly Diagnosed Immune Thrombo-cytopaenia. British Journal of Haematology, 184, 288-290. https://doi.org/10.1111/bjh.15070 |
| [40] | Kuter, D. and Begley, C. (2002) Recombinant Human Thrombopoietin: Basic Biology and Evaluation of Clinical Studies. Blood, 100, 3457-3469. https://doi.org/10.1182/blood.V100.10.3457 |
| [41] | 顾小慧, 赵凤晓, 尹淑荣. 艾曲波帕联合重组人血小板生成素治疗难治性血小板减少性紫癜的疗效分析[J]. 中外医疗, 2020, 39(2): 101-103. |
| [42] | 李蒲, 胡锦芳. 艾曲泊帕乙醇胺片联合重组人血小板生成素注射液治疗血小板减少症患者的临床研究[J]. 中国临床药理学杂志, 2020, 36(7): 750-752. |
| [43] | 安博文. 艾曲泊帕乙醇胺片联合重组人血小板生成素注射液治疗原发免疫性血小板减少症患者的效果和安全性分析[J]. 黑龙江医学, 2023, 47(14): 1717-1720. |
| [44] | 刘雪娜. TPO受体激动剂治疗原发免疫性血小板减少症的相关研究[D]: [博士学位论文]. 济南: 山东大学, 2017.
https://doi.org/10.7666/d.Y3238702 |
| [45] | Kahan, B. (1989) Cyclosporine. New England Journal of Medicine, 321, 1725-1738.
https://doi.org/10.1056/NEJM198912213212507 |
| [46] | 周茉, 邵钰, 单学赟, 等. 艾曲泊帕联合环孢素治疗难治性免疫性血小板减少症的效果观察[J]. 实用临床医药杂志, 2022, 26(10): 51-53. |
| [47] | 曹利红, 潘琦, 范翠华, 等. 艾曲波帕联合环孢素A治疗免疫性血小板减少症的效果观察[J]. 浙江医学, 2021, 43(9): 996-998, 1002. |
| [48] | 张浩, 薛阿利, 冯爱梅, 等. 环孢素A联合硫唑嘌呤治疗对糖皮质激素或脾切除无效的免疫性血小板减少症[J]. 浙江临床医学, 2014(10): 1625-1626. |
| [49] | 马永华, 罗达似, 夏天, 等. 艾曲波帕与硫唑嘌呤联合治疗难治性ITP的效果[J]. 深圳中西医结合杂志, 2021, 31(24): 101-103. |
| [50] | 罗洪强, 钟永根, 封蔚莹. 艾曲波帕联合硫唑嘌呤治疗难治性特发性血小板减少性紫癜的疗效及其对细胞免疫功能的影响研究[J]. 中国全科医学, 2019, 22(21): 2588-2592. |
| [51] | 徐露露, 黄建尧, 蔡露青, 等. 艾曲波帕联合硫唑嘌呤治疗RITP的疗效及其作用机制研究[J]. 现代生物医学进展, 2021, 21(5): 911-914. |
| [52] | 曹新甜, 胡晓梅, 孙妍, 等. 艾曲波帕联合用药治疗成人原发免疫性血小板减少症的有效性及安全性系统评价[J]. 临床血液学杂志, 2021, 34(7): 495-501. |
