Cole Ashley L, Wood William A, Muluneh Benyam, Lund Jennifer L, Elston Lafata Jennifer, Dusetzina Stacie B
Division of Pharmaceutical Outcomes and Policy, University of North Carolina (UNC) Eshelman School of Pharmacy, Chapel Hill, NC.
Cecil G. Sheps Center for Health Services Research, Chapel Hill, NC.
JCO Oncol Pract. 2020 May;16(5):e443-e455. doi: 10.1200/JOP.19.00301. Epub 2020 Mar 20.
Tyrosine kinase inhibitors (TKIs) have dramatically improved survival for patients with chronic myeloid leukemia (CML). No overall survival differences were observed between patients initiating first- and second-generation TKIs in trials; however, real-world safety and cost outcomes are unclear. We evaluated comparative safety and health care expenditures between first-line imatinib, dasatinib, and nilotinib among patients with CML.
Eligible patients had one or more fills for imatinib, dasatinib, or nilotinib in the MarketScan Commercial and Medicare Supplemental databases between January 1, 2011, and December 31, 2016 (earliest fill is the index date), 6 months pre-index continuous enrollment, CML diagnosis, and no TKI use in the pre-index period. Hospitalizations or emergency department visits (safety events) were compared across treatment groups using propensity-score-weighted 1-year relative risks (RRs) and subdistribution hazard ratios (HRs). Inflation-adjusted annual health care expenditures were compared using quantile regression.
Eligible patients included 1,417 receiving imatinib, 1,067 receiving dasatinib, and 647 receiving nilotinib. The 1-year risk of safety events was high: imatinib, 37%; dasatinib, 44%; and nilotinib, 40%, with higher risks among patients receiving dasatinib (RR, 1.17; 95% CI, 1.06 to 1.30) and nilotinib (RR, 1.07; 95% CI, 0.93 to 1.23) compared with those receiving imatinib. Over a median of 1.7 years, the cumulative incidence of safety events was higher among patients receiving dasatinib (HR, 1.23; 95% CI, 1.10 to 1.38) and nilotinib (HR, 1.08; 95% CI, 0.95 to 1.24) than among those receiving imatinib. One-year health care expenditures were high (median, $125,987) and were significantly higher among patients initiating second-generation TKIs compared with those receiving imatinib (difference in medians: dasatinib imatinib, $22,393; 95% CI, $17,068 to $27,718; nilotinib imatinib, $19,463; 95% CI, $14,689 to $24,236).
Patients receiving imatinib had the lowest risk of hospitalization or emergency department visits and 1-year health care expenditures. Given a lack of significant differences in overall survival, imatinib may represent the ideal first-line therapy for patients, on average.
酪氨酸激酶抑制剂（TKIs）显著提高了慢性髓性白血病（CML）患者的生存率。在试验中，起始使用第一代和第二代TKIs的患者之间未观察到总生存差异；然而，真实世界中的安全性和成本结果尚不清楚。我们评估了CML患者中一线使用伊马替尼、达沙替尼和尼洛替尼的安全性和医疗保健支出的比较情况。
符合条件的患者在2011年1月1日至2016年12月31日期间在MarketScan商业和医疗保险补充数据库中有一次或多次伊马替尼、达沙替尼或尼洛替尼的配药记录（最早配药日期为索引日期），索引前连续参保6个月，有CML诊断，且在索引前期未使用TKI。使用倾向评分加权的1年相对风险（RRs）和亚分布风险比（HRs）比较各治疗组的住院或急诊就诊情况（安全事件）。使用分位数回归比较经通胀调整的年度医疗保健支出。
符合条件的患者包括1417例接受伊马替尼治疗、1067例接受达沙替尼治疗和647例接受尼洛替尼治疗的患者。安全事件的1年风险较高：伊马替尼为37%；达沙替尼为44%；尼洛替尼为40%，接受达沙替尼（RR，1.17；95%CI，1.06至1.30）和尼洛替尼（RR，1.07；95%CI，0.93至1.23）的患者与接受伊马替尼的患者相比风险更高。在中位1.7年的时间里，接受达沙替尼（HR，1.23；95%CI，1.10至1.38）和尼洛替尼（HR，1.08；95%CI，0.95至1.24）的患者安全事件的累积发生率高于接受伊马替尼的患者。1年医疗保健支出较高（中位数为125,987美元），起始使用第二代TKIs的患者与接受伊马替尼的患者相比显著更高（中位数差异：达沙替尼-伊马替尼为22,393美元；95%CI，17,068美元至27,718美元；尼洛替尼-伊马替尼为19,463美元；95%CI，14,689美元至24,236美元）。
接受伊马替尼治疗的患者住院或急诊就诊风险以及1年医疗保健支出最低。鉴于总生存无显著差异，平均而言，伊马替尼可能是患者理想的一线治疗药物。
