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慢性髓性白血病中一线酪氨酸激酶抑制剂的使用模式及转换至二线治疗的时间

Use patterns of first-line inhibitors of tyrosine kinase and time to change to second-line therapy in chronic myeloid leukemia.

作者信息

Machado-Alba Jorge Enrique, Machado-Duque Manuel Enrique

机构信息

Grupo de Investigación en Farmacoepidemiología y Farmacovigilancia, Facultad Ciencias de la Salud-Programa de Medicina, Universidad Tecnológica de Pereira- Audifarma S.A., Paraje la Julita, AA: 97, Pereira, Risaralda, 660003, Colombia.

出版信息

Int J Clin Pharm. 2017 Aug;39(4):851-859. doi: 10.1007/s11096-017-0484-9. Epub 2017 May 15.

Abstract

Background Chronic myeloid leukemia (CML) has a low incidence but a high burden of disease, and is treated with high-cost tyrosine kinase inhibitors (TKI). Objective To determine the time from the start of a first-line TKI until it passes to second-line, and to establish the reasons for the change of therapy time. Setting Patients with Philadelphia-positive CML treated with some TKI. Methods Retrospective cohort study, between January 1 2007 and July 31 2015, with information obtained from medical records, the time to change initial drugs to secondline therapy, and the reasons for change, were identified. Kaplan-Meier survival analysis was carried out. Main outcome measure A change in therapy to the secondline TKI and the final reason for the change of therapy. Results A total of 247 patients treated were found in 22 cities in Colombia with a mean age of 53.2 ± 15.2 years. The drug most used as initial therapy was imatinib; 53.8% of cases had to change to another TKI. 50% of patients changed therapy in 42 months, men in 24 and women in 67 months (95% CI 14.314-33.686; p = 0.001). Being male (OR 2.23; 95% CI 1.291-3.854; p = 0.004) and receiving hydroxyurea (OR 3.65; 95% CI 1.601-8.326; p = 0.002) were associated with a higher probability of switching to nilotinib or dasatinib, while receiving a new-generation TKI (OR 0.15; 95% CI 0.071-0.341; p < 0.001) reduced this risk. Conclusions A high proportion of patients needed to change to a second line with nilotinib and dasatinib management. It is necessary to obtain more real world evidence, to improve the effectiveness, adherence and safety of the treatment.

摘要

背景

慢性髓性白血病(CML)发病率低但疾病负担高,需使用高成本的酪氨酸激酶抑制剂(TKI)进行治疗。目的:确定一线TKI治疗开始至转为二线治疗的时间,并明确治疗时间改变的原因。研究地点:接受某种TKI治疗的费城染色体阳性CML患者。方法:回顾性队列研究,时间跨度为2007年1月1日至2015年7月31日,从病历中获取信息,确定初始药物更换为二线治疗的时间及更换原因,并进行Kaplan-Meier生存分析。主要观察指标:二线TKI治疗的改变及治疗改变的最终原因。结果:在哥伦比亚22个城市共发现247例接受治疗的患者,平均年龄为53.2±15.2岁。最常用作初始治疗的药物是伊马替尼;53.8%的病例不得不更换为另一种TKI。50%的患者在42个月时更换治疗,男性为24个月,女性为67个月(95%CI 14.314 - 33.686;p = 0.001)。男性(OR 2.23;95%CI 1.291 - 3.854;p = 0.004)和接受羟基脲治疗(OR 3.65;95%CI 1.601 - 8.326;p = 0.002)与改用尼罗替尼或达沙替尼的可能性较高相关,而接受新一代TKI治疗(OR 0.15;95%CI 0.071 - 0.341;p < 0.001)可降低这种风险。结论:很大一部分患者需要更换为尼罗替尼和达沙替尼管理的二线治疗。有必要获取更多真实世界证据,以提高治疗的有效性、依从性和安全性。

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