Department of Rheumatology, CHRU de Tours, Tours, France.
EA 7501 GICC, Université de Tours, Tours, France.
RMD Open. 2021 Nov;7(3). doi: 10.1136/rmdopen-2021-001882.
To identify patient characteristics associated with responsiveness to tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA).
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.
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).
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.
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。
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。
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)。
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。