Durkin Michael, Blais Jaime
Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA.
Diabetes Ther. 2021 Feb;12(2):499-508. doi: 10.1007/s13300-020-00953-4. Epub 2020 Dec 18.
Diabetes is a common cause of end-stage kidney disease leading to dialysis or kidney transplantation. Estimated glomerular filtration rate (eGFR) measures kidney function, and differences in the rate (slope) of eGFR decline can be used to assess treatment effects on kidney function over time. In the CREDENCE trial, the sodium glucose co-transporter 2 inhibitor canagliflozin slowed the rate of eGFR decline by 60% compared to placebo in patients with diabetes and chronic kidney disease. This analysis utilized eGFR slopes from CREDENCE to estimate the difference in time to dialysis by treatment arm and estimated the economic value of that delay.
A linear decline in eGFR and maintenance of stable therapy were assumed for the canagliflozin and placebo arms in CREDENCE. Mean eGFR over time was calculated using acute (baseline to week 3) and chronic (week 3 onward) slopes. Reaching eGFR of 10 ml/min/1.73 m was assumed to represent the need for chronic dialysis. The difference in time to dialysis between treatments was calculated. Based on the average duration of dialysis, annual dialysis costs were determined, discounting 2020 US dollars at an inflation rate of 4%.
Following the acute and chronic eGFR slopes, the projected time to dialysis was 22.85 years for canagliflozin and 9.90 years for placebo. Based on 95% confidence intervals from CREDENCE, the model-estimated difference in time to dialysis was 9.27-17.48 years. With a mean baseline participant age of 63 years, the delay in dialysis with canagliflozin would be associated with a reduction in dialysis costs of approximately $170,000 per patient in 2020 dollars.
Using clinical trial data, canagliflozin treatment was projected to delay dialysis by approximately 13 years, which could translate to a substantial cost savings. More precise estimates should be investigated with considerations for nonlinear eGFR slope trajectory, competing risks, and patient characteristics.
ClinicalTrials.gov identifier, NCT02065791.
糖尿病是导致终末期肾病进而需要透析或肾移植的常见病因。估算肾小球滤过率（eGFR）可衡量肾功能，eGFR下降速率（斜率）的差异可用于评估一段时间内治疗对肾功能的影响。在CREDENCE试验中，与安慰剂相比，钠-葡萄糖协同转运蛋白2抑制剂卡格列净使糖尿病和慢性肾病患者的eGFR下降速率减缓了60%。本分析利用CREDENCE试验中的eGFR斜率来估计各治疗组至透析时间的差异，并估算该延迟的经济价值。
假定CREDENCE试验中卡格列净组和安慰剂组的eGFR呈线性下降且治疗维持稳定。使用急性（基线至第3周）和慢性（第3周及以后）斜率计算随时间变化的平均eGFR。假定eGFR达到10 ml/min/1.73 m²代表需要进行长期透析。计算各治疗组至透析时间的差异。根据透析的平均时长确定年度透析费用，按4%的通货膨胀率对2020年美元进行贴现。
按照急性和慢性eGFR斜率，卡格列净组预计至透析时间为22.85年，安慰剂组为9.90年。根据CREDENCE试验的95%置信区间，模型估计的至透析时间差异为9.27 - 17.48年。参与者的平均基线年龄为63岁，使用卡格列净延迟透析将使每位患者的透析费用在2020年美元的基础上减少约170,000美元。
根据临床试验数据，预计卡格列净治疗可使透析延迟约13年，这可能带来可观的成本节约。应考虑非线性eGFR斜率轨迹、竞争风险和患者特征，对更精确的估计进行研究。
ClinicalTrials.gov标识符，NCT02065791。
