Clinical and biochemical factors associated with risk of total joint replacement and radiographic progression in osteoarthritis: Data from two phase III clinical trials
Clinical and biochemical factors associated with risk of total joint replacement and radiographic progression in osteoarthritis: Data from two phase III clinical trials
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DOI：
10.1016/j.semarthrit.2020.03.002
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发表时间：
2020-12-01
影响因子：
5
通讯作者：
Bay-Jensen, Anne-Christine
中科院分区：
文献类型：
--
作者：
Bihlet, Asger Reinstrup;Bjerre-Bastos, Jonathan Jetsmark;Bay-Jensen, Anne-Christine
目的：骨关节炎的新疾病改善治疗的临床试验必须证明对功能结果或减少关节衰竭有积极作用，才能被认为是成功的。全关节置换术（TJR）手术可能被认为是关节衰竭，但TJR发生率的巨大差异使其作为研究终点复杂化。预测TJR风险升高的因素可能被用来丰富这类结果试验。方法：使用来自1255例膝关节OA患者尿液样本的两项三期临床试验的累积数据，我们评估了一系列基线临床变量的价值，包括ucx - ii生物标志物，作为关节间隙狭窄、kellgren - lawrence级进展和全关节置换术的预测因子。结果：结合年龄、性别、BMI、CTX-II和kl分级的预测模型预测两年内TJR的AUC为0.75 （95% CI: 0.72-0.77）。在研究期间，膝关节间累积kl等级为5,6或7的参与者发生TJR的风险比较低的参与者高出3倍以上（HR: 3.03, 95% CI: 1.54至5.96,p = 0.001）。年龄与TJR风险增加相关（每5岁：HR: 1.28, 95% CI: 1.03-3.79, p = 0.05）。基线u-CTX-II与JSN和kl级放射学进展风险升高相关。结论：结合基线年龄、性别、BMI、u-CTX-II和kl分级的复合模型能够在两年内可接受地预测TJR。在没有基线骨关节炎严重程度的情况下，u-CTX-II独立地预测了TJR。基线尿液CTX-II与影像学进展风险相关。(C) 2020爱思唯尔公司版权所有。
Objectives: Clinical trials of new disease-modifying treatments for osteoarthritis should demonstrate a positive effect on a functional outcome or reduction in joint failure in order to be considered successful. Total joint replacement (TJR) surgery may be considered as joint failure, but great variation in the incidence of TJR complicates its use as a study endpoint. Factors predicting elevated risk of TJR could potentially be used to enrich such outcome-trials.Methods: Using cumulative data from two phase three clinical trials with urine samples from 1255 knee OA patients followed for two years, we assessed the value of a series of baseline clinical variables including the uCTX-II biomarker, as predictors of joint-space narrowing, Kellgren-Lawrence-grade progression, and total joint replacement.Results: A prediction-model incorporating age, sex, BMI, CTX-II and KL-grade predicted TJR within the two-year period with an AUC of 0.75 (95% CI: 0.72-0.77). The participants with a cumulative KL-grade between knees of 5, 6, or 7 had a more than 3 times higher risk of TJR in the study period compared to lower (HR: 3.03, 95% CI: 1.54 to 5.96, p = 0.001). Age was associated with increased TJR risk (per 5 years of age: HR: 1.28, 95% CI: 1.03-3.79, p = 0.05). Baseline u-CTX-II was associated with elevated risk of radiographic progression in terms of both JSN and KL-grade.Conclusions: A composite model combining baseline age, sex, BMI, u-CTX-II and KL-grade was able to acceptably predict TJR during a two-year period. In the absence of baseline radiographic OA severity, u-CTX-II independently contributed to prediction of TJR. Baseline urine CTX-II was associated with risk of radiographic progression. (C) 2020 Elsevier Inc. All rights reserved.