Machado-Alba Jorge Enrique, Machado-Duque Manuel Enrique
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.
Int J Clin Pharm. 2017 Aug;39(4):851-859. doi: 10.1007/s11096-017-0484-9. Epub 2017 May 15.
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.
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。
