Abstract：
BACKGROUND: This is the first US-representative, retrospective, real-world propensity score (PS) matching study comparing the occurrence of TLS-associated fatalities following allopurinol monotherapy versus rasburicase monotherapy. We have previously found rasburicase significantly and more rapidly reduces uric acid exposure (AUC) compared to allopurinol in patients with or at risk of TLS (Goldman/Cairo et al., Blood, 2001).
OBJECTIVE: To determine if a significant difference exists in the proportion of TLS-associated fatalities following treatment with allopurinol or rasburicase monotherapy for having or being at risk of TLS.
METHODS: 282 rasburicase and allopurinol patients were PS-matched for TLS risk using eleven predictive covariates. Patients were matched 1:1 using calipers of width equal to 0.2 of the standard deviation of the logit of the PS (d score). The overall PS logit was almost 0.6 before matching but near 0.0 afterward; covariates exhibited only a small imbalance (|d|<0 .25), indicating patients were well matched.
METHODS: Anonymized patient information from our 2021 physician-based, blinded, retrospective study, provided by 266 oncologists from US physician-owned practices, academic and non-academic hospitals, and outpatient clinics.
METHODS: Fielded June-September, the 2021 study included 715 randomized liquid-tumor patients treated in the past year for hyperuricemia (HU) risk and TLS potential. The 2022 PSM analysis included only those receiving rasburicase or allopurinol monotherapy and excluded patients with spontaneous TLS or TLS before HU treatment, leaving 533 potential subjects. 282 were matched on PS and eleven pre-HU treatment covariates: acute renal failure, age, anti-cancer regimen, creatinine, gender, lactate dehydrogenase, perceived risk, renal disease, tumor type, uric acid, and white blood count. Unmatched cases were discarded.
METHODS: Proportions of mortalities that physicians said were the direct result of TLS. The null hypothesis before matching was no significant difference between the groups.
RESULTS: Analyzing all matched patients (n=141 in each group), regardless of TLS development following HU treatment, TLS-associated mortality was significantly less likely among rasburicase patients (2.1% vs. 7.1% [P-value 0.047]). Analyzing the subset who developed TLS after HU treatment, TLS-associated fatalities were even less likely among rasburicase patients, 3 of 36 rasburicase vs. 10 of 27 allopurinol patients [P-value 0.005].
CONCLUSIONS: Results indicate rasburicase compared to allopurinol significantly reduces TLS-associated fatalities.
OBJECTIVE: To determine if a significant difference exists in the proportion of TLS-associated fatalities following treatment with allopurinol or rasburicase monotherapy for having or being at risk of TLS.
METHODS: 282 rasburicase and allopurinol patients were PS-matched for TLS risk using eleven predictive covariates. Patients were matched 1:1 using calipers of width equal to 0.2 of the standard deviation of the logit of the PS (d score). The overall PS logit was almost 0.6 before matching but near 0.0 afterward; covariates exhibited only a small imbalance (|d|<0 .25), indicating patients were well matched.
METHODS: Anonymized patient information from our 2021 physician-based, blinded, retrospective study, provided by 266 oncologists from US physician-owned practices, academic and non-academic hospitals, and outpatient clinics.
METHODS: Fielded June-September, the 2021 study included 715 randomized liquid-tumor patients treated in the past year for hyperuricemia (HU) risk and TLS potential. The 2022 PSM analysis included only those receiving rasburicase or allopurinol monotherapy and excluded patients with spontaneous TLS or TLS before HU treatment, leaving 533 potential subjects. 282 were matched on PS and eleven pre-HU treatment covariates: acute renal failure, age, anti-cancer regimen, creatinine, gender, lactate dehydrogenase, perceived risk, renal disease, tumor type, uric acid, and white blood count. Unmatched cases were discarded.
METHODS: Proportions of mortalities that physicians said were the direct result of TLS. The null hypothesis before matching was no significant difference between the groups.
RESULTS: Analyzing all matched patients (n=141 in each group), regardless of TLS development following HU treatment, TLS-associated mortality was significantly less likely among rasburicase patients (2.1% vs. 7.1% [P-value 0.047]). Analyzing the subset who developed TLS after HU treatment, TLS-associated fatalities were even less likely among rasburicase patients, 3 of 36 rasburicase vs. 10 of 27 allopurinol patients [P-value 0.005].
CONCLUSIONS: Results indicate rasburicase compared to allopurinol significantly reduces TLS-associated fatalities.
摘要：
背景：这是第一位美国代表，回顾性,真实世界倾向评分(PS)匹配研究,比较别嘌呤醇单药治疗与rasburicase单药治疗后TLS相关死亡发生率.我们以前发现，在患有TLS或有TLS风险的患者中，与别嘌呤醇相比，rasburicase显着且更快地降低了尿酸暴露（AUC）（Goldman/Cairo等人。,血，2001).
目的：确定使用别嘌呤醇或rasburicase单药治疗后，TLS相关死亡比例是否存在显著差异。
方法：282例rasburicase和别嘌醇患者使用11个预测协变量对TLS风险进行PS匹配。使用宽度等于PS的logit的标准偏差的0.2(d评分)的卡尺以1:1匹配患者。总体PSlogit在匹配前几乎为0.6，但在匹配后接近0.0；协变量仅表现出很小的不平衡(|d|<0.25)，表明患者匹配良好。
方法：匿名的患者信息来自我们2021年的医师，失明,回顾性研究,由266名美国医师拥有的肿瘤学家提供，学术和非学术医院，和门诊诊所。
方法：6月至9月，2021年的研究包括715例过去一年接受过高尿酸血症(HU)风险和TLS潜能治疗的随机液体肿瘤患者.2022年PSM分析仅包括接受rasburicase或别嘌呤醇单药治疗的患者，并在HU治疗前排除自发性TLS或TLS的患者。留下533个潜在的受试者。282在PS和11个HU治疗前协变量上匹配：急性肾衰竭，年龄,抗癌方案，肌酐,性别,乳酸脱氢酶,感知风险，肾脏疾病,肿瘤类型,尿酸,和白细胞计数。不匹配的病例被丢弃。
方法：医生所说的死亡率是TLS的直接结果。匹配前的零假设在各组之间没有显着差异。
结果：分析所有匹配的患者（每组n=141），无论HU治疗后的TLS发展如何，在rasburicase患者中，与TLS相关的死亡率显着降低（2.1％与7.1%[P值0.047])。分析HU治疗后出现TLS的子集，在rasburicase患者中，TLS相关死亡的可能性更小，3of36rasburicasevs.27例别嘌醇患者中的10例[P值0.005]。
结论：结果表明，与别嘌呤醇相比，rasburicase可显著降低TLS相关死亡率。
目的：确定使用别嘌呤醇或rasburicase单药治疗后，TLS相关死亡比例是否存在显著差异。
方法：282例rasburicase和别嘌醇患者使用11个预测协变量对TLS风险进行PS匹配。使用宽度等于PS的logit的标准偏差的0.2(d评分)的卡尺以1:1匹配患者。总体PSlogit在匹配前几乎为0.6，但在匹配后接近0.0；协变量仅表现出很小的不平衡(|d|<0.25)，表明患者匹配良好。
方法：匿名的患者信息来自我们2021年的医师，失明,回顾性研究,由266名美国医师拥有的肿瘤学家提供，学术和非学术医院，和门诊诊所。
方法：6月至9月，2021年的研究包括715例过去一年接受过高尿酸血症(HU)风险和TLS潜能治疗的随机液体肿瘤患者.2022年PSM分析仅包括接受rasburicase或别嘌呤醇单药治疗的患者，并在HU治疗前排除自发性TLS或TLS的患者。留下533个潜在的受试者。282在PS和11个HU治疗前协变量上匹配：急性肾衰竭，年龄,抗癌方案，肌酐,性别,乳酸脱氢酶,感知风险，肾脏疾病,肿瘤类型,尿酸,和白细胞计数。不匹配的病例被丢弃。
方法：医生所说的死亡率是TLS的直接结果。匹配前的零假设在各组之间没有显着差异。
结果：分析所有匹配的患者（每组n=141），无论HU治疗后的TLS发展如何，在rasburicase患者中，与TLS相关的死亡率显着降低（2.1％与7.1%[P值0.047])。分析HU治疗后出现TLS的子集，在rasburicase患者中，TLS相关死亡的可能性更小，3of36rasburicasevs.27例别嘌醇患者中的10例[P值0.005]。
结论：结果表明，与别嘌呤醇相比，rasburicase可显著降低TLS相关死亡率。
