Zhou Xiaolei, Davenport Eric, Ouyang John, Hoke Molly E, Garbinsky Diana, Agarwal Indra, Krasa Holly B, Oberdhan Dorothee
RTI Health Solutions, Research Triangle Park, North Carolina, USA.
Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland, USA.
Kidney Int Rep. 2022 Feb 19;7(5):1037-1048. doi: 10.1016/j.ekir.2022.02.009. eCollection 2022 May.
In 1- and 3-year randomized trials, tolvaptan slowed kidney function decline in subjects with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. The 3-year trial also evaluated effects on total kidney volume (TKV); slowing of TKV growth was demonstrated. Subjects were followed in open-label extension trials. To characterize longer-term effects of treatment, an analysis was conducted comparing tolvaptan-treated subjects with subjects from standard of care (SOC) ADPKD studies without tolvaptan.
This was a pooled, longitudinal analysis of data from 8 tolvaptan clinical trials and 5 studies without tolvaptan (natural history or SOC) in ADPKD. Data from subjects who participated in multiple studies were linked for longer follow-up. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and TKV over 5.5 years. To control for heterogeneity in disease characteristics between tolvaptan and SOC treatment groups, analysis populations matched for baseline demographic and disease characteristics were constructed.
Matched analysis ( 1186 in each treatment group) indicated that tolvaptan slowed annualized eGFR decline by 1.01 ml/min per 1.73 m ( < 0.001) versus SOC over 5.5 years. An analysis conducted on the full, unmatched data set (tolvaptan: 2928; SOC: 4189) confirmed significant reduction in annual eGFR decline. Among subjects with TKV data, TKV was significantly reduced at years 1, 3, and 5 for tolvaptan versus SOC in both matched and full data sets.
Comparison of a pooled tolvaptan cohort to a pooled control cohort with ADPKD supports longer-term treatment effects of tolvaptan.
在1年和3年的随机试验中，托伐普坦减缓了有快速进展风险的常染色体显性多囊肾病（ADPKD）患者的肾功能下降。3年试验还评估了对总肾体积（TKV）的影响；证实了TKV生长减缓。在开放标签延长试验中对受试者进行了随访。为了描述治疗的长期效果，进行了一项分析，将接受托伐普坦治疗的受试者与未使用托伐普坦的常染色体显性多囊肾病标准治疗（SOC）研究中的受试者进行比较。
这是一项对8项托伐普坦临床试验和5项ADPKD中未使用托伐普坦（自然病史或SOC）研究的数据进行汇总的纵向分析。参与多项研究的受试者的数据被关联起来以进行更长时间的随访。结局指标是5.5年内估计肾小球滤过率（eGFR）和TKV的变化率。为了控制托伐普坦和SOC治疗组之间疾病特征的异质性，构建了基线人口统计学和疾病特征匹配的分析人群。
匹配分析（每个治疗组1186例）表明，在5.5年的时间里，与SOC相比，托伐普坦使eGFR年化下降速度减慢了1.01 ml/min/1.73 m²（P<0.001）。对完整的、未匹配的数据集（托伐普坦组：2928例；SOC组：4189例）进行的分析证实，年度eGFR下降显著减少。在有TKV数据的受试者中，在匹配和完整数据集中，托伐普坦组与SOC组相比，在第1、3和5年时TKV均显著降低。
将托伐普坦汇总队列与ADPKD对照汇总队列进行比较，支持托伐普坦的长期治疗效果。
