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类风湿关节炎对 TNF 抑制剂应答的预测因素:随机对照试验的个体患者数据汇总分析。

Predictors of response to TNF inhibitors in rheumatoid arthritis: an individual patient data pooled analysis of randomised controlled trials.

机构信息

Department of Rheumatology, CHRU de Tours, Tours, France.

EA 7501 GICC, Université de Tours, Tours, France.

出版信息

RMD Open. 2021 Nov;7(3). doi: 10.1136/rmdopen-2021-001882.

Abstract

OBJECTIVE

To identify patient characteristics associated with responsiveness to tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA).

MATERIALS AND METHODS

Individual patient data from 29 randomised controlled trials (RCTs) evaluating the efficacy of a TNFi versus placebo or conventional therapy were obtained. Response to treatment was assessed in subgroups according to the following baseline characteristics: smoking status, physical activity, sex, age, body mass index, autoantibody profile, disease duration, high initial disease activity defined by Disease Activity Score on 28 joints (DAS28)(C reactive protein (CRP)) >5.1. The primary outcome was the between-treatment group difference in DAS28(CRP) change from baseline to 6 months. The secondary endpoints were the between-treatment group difference in final DAS28(CRP) measured until 6 months and EULAR response criteria until 6 months. Data from each RCT were then pooled by the Mantel-Haenszel method using a random effects model. A linear metaregression was also carried out on two data-sharing platforms separately to support the results.

RESULTS

Individual data of 11 617 patients from 29 RCTs were analysed. Until 6 months, a significantly higher EULAR non-response rate was observed in obese patients (OR 0.52 vs 0.36 for non-obese, p=0.01). A multivariable regression model performed on 7457 patients indicated that patients treated by TNFi had a final DAS28(CRP) decreased by 0.02 for each year of disease duration (p<0.001), and a 0.21 decreased for patients with a baseline DAS28(CRP) >5.1 (p<0.001).

CONCLUSIONS

In RA, patients who are more responsive to TNFi are those who are non-obese, have a long disease duration and have a high initial disease activity.

摘要

目的

确定与类风湿关节炎(RA)中肿瘤坏死因子抑制剂(TNFi)反应相关的患者特征。

材料和方法

从评估 TNFi 与安慰剂或常规治疗疗效的 29 项随机对照试验(RCT)中获得了个体患者数据。根据以下基线特征,根据亚组评估治疗反应:吸烟状况、身体活动、性别、年龄、体重指数、自身抗体谱、疾病持续时间、高初始疾病活动定义为 28 关节疾病活动评分(DAS28)(C 反应蛋白(CRP))>5.1。主要结局是从基线到 6 个月时 DAS28(CRP)变化的治疗组间差异。次要终点是直到 6 个月时最终 DAS28(CRP)的治疗组间差异和直到 6 个月时 EULAR 反应标准。然后,通过 Mantel-Haenszel 方法使用随机效应模型汇总每个 RCT 的数据。还分别在两个数据共享平台上进行了线性荟萃回归,以支持结果。

结果

分析了来自 29 项 RCT 的 11617 名患者的个体数据。直到 6 个月,肥胖患者的 EULAR 无反应率明显更高(非肥胖患者的 OR 为 0.52,肥胖患者的 OR 为 0.36,p=0.01)。对 7457 名患者进行的多变量回归模型表明,TNFi 治疗的患者疾病持续时间每增加 1 年,DAS28(CRP)最终降低 0.02(p<0.001),DAS28(CRP)基线>5.1 的患者降低 0.21(p<0.001)。

结论

在 RA 中,对 TNFi 反应更好的患者是非肥胖患者、疾病持续时间较长且初始疾病活动较高的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44f7/8601061/34d82c823ab1/rmdopen-2021-001882f01.jpg

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