Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy
Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy
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DOI：
10.2215/cjn.08600718
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发表时间：
2019-03-07
影响因子：
9.8
通讯作者：
Nachman, Patrick H.
中科院分区：
文献类型：
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作者：
Thompson, Aliza;Carroll, Kevin;Nachman, Patrick H.
IgA 肾病 (IgAN) 是 ESKD 的一个重要原因，目前尚无批准的治疗方法。评估 IgAN 治疗的一个挑战是进展为 ESKD 的通常较长时间过程。该肾脏健康倡议项目的目的是确定替代终点，这些终点可以作为治疗对 IgAN 长期肾脏结局影响的可靠预测指标，并用作批准的基础。蛋白尿被认为是 IgAN 进展为 ESKD 的最广泛认可和充分研究的危险因素。该工作组对蛋白尿减少的数据进行了严格审查，将其作为治疗对 IgAN 进展为 ESKD 的影响的替代终点。流行病学数据表明蛋白尿的水平和持续时间与肾功能丧失之间存在密切且一致的关系。对 13 项对照试验数据的试验水平分析还显示，蛋白尿减少百分比的治疗效果与血清肌酐倍增时间、ESKD 或死亡的综合治疗效果之间存在关联。我们得出的结论是，数据支持使用蛋白尿减少作为治疗对 IgAN 进展为 ESKD 的影响的合理可能的替代终点。在美国，合理可能的替代终点可用作加速批准旨在治疗严重或危及生命的疾病（例如 IgAN）的疗法的基础。根据该计划批准的产品的临床益处需要在上市后验证性试验中得到验证。
IgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgAN is the usual long time course for progression to ESKD. The aim of this Kidney Health Initiative project was to identify surrogate end points that could serve as reliable predictors of a treatment's effect on long-term kidney outcomes in IgAN and be used as a basis for approval. Proteinuria was identified as the most widely recognized and well studied risk factor for progression to ESKD in IgAN. The workgroup performed a critical review of the data on proteinuria reduction as a surrogate end point for a treatment's effect on progression to ESKD in IgAN. Epidemiologic data indicate a strong and consistent relationship between the level and duration of proteinuria and loss of kidney function. Trial-level analyses of data from 13 controlled trials also show an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death. We conclude that data support the use of proteinuria reduction as a reasonably likely surrogate end point for a treatment's effect on progression to ESKD in IgAN. In the United States, reasonably likely surrogate end points can be used as a basis for accelerated approval of therapies intended to treat serious or life-threatening conditions, such as IgAN. The clinical benefit of products approved under this program would need to be verified in a postmarketing confirmatory trial.