Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Rheumatology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Ann Rheum Dis. 2018 Sep;77(9):1261-1267. doi: 10.1136/annrheumdis-2018-213035. Epub 2018 May 14.
To identify and validate clinical baseline predictors associated with inadequate response (IR) to methotrexate (MTX) therapy in newly diagnosed patients with rheumatoid arthritis (RA).
In U-Act-Early, 108 disease-modifying antirheumatic drug (DMARD)-naive patients with RA were randomised to initiate MTX therapy and treated to target until sustained remission (disease activity score assessing 28 joints (DAS28) <2.6 with four or less swollen joints for ≥24 weeks) was achieved. If no remission, hydroxychloroquine was added to the treatment regimen (ie, 'MTX+') and replaced by tocilizumab if the target still was not reached thereafter. Regression analyses were performed to identify clinical predictors for IR, defined as needing addition of a biological DMARD, to 'MTX+'. Data from the treatment in the Rotterdam Early Arthritis Cohort were used for external validation of the prediction model.
Within 1 year, 56/108 (52%) patients in U-Act-Early showed IR to 'MTX+'. DAS28 (adjusted OR (OR) 2.1, 95% CI 1.4 to 3.2), current smoking (OR 3.02, 95% CI 1.1 to 8.0) and alcohol consumption (OR 0.4, 95% CI 0.1 to 0.9) were identified as baseline predictors. The area under the receiver operator characteristic curve (AUROC) of the prediction model was 0.75 (95% CI 0.66 to 0.84); the positive (PPV) and negative predictive value (NPV) were 65% and 80%, respectively. When applying the model to the validation cohort, the AUROC slightly decreased to 0.67 (95% CI 0.55 to 0.79) and the PPV and NPV to 54% and 80%, respectively.
Higher DAS28, current smoking and no alcohol consumption are predictive factors for IR to step-up 'MTX+' in DMARD-naive patients with new-onset RA.
NCT01034137; Post-results, ISRCTN26791028; Post-results.
确定并验证与新诊断的类风湿关节炎（RA）患者甲氨蝶呤（MTX）治疗反应不足（IR）相关的临床基线预测因素。
在 U-Act-Early 中，108 名初治的疾病修饰抗风湿药物（DMARD）患者被随机分配接受 MTX 治疗，并在达到持续缓解（28 个关节疾病活动评分（DAS28）<2.6，且≥24 周内有 4 个以下肿胀关节）的目标之前接受治疗。如果没有缓解，则将羟氯喹添加到治疗方案中（即“MTX+”），如果此后仍未达到目标，则用托珠单抗替代。进行回归分析以确定需要添加生物 DMARD 的 IR 的临床预测因素，定义为需要添加生物 DMARD。使用鹿特丹早期关节炎队列的治疗数据对预测模型进行外部验证。
在 1 年内，U-Act-Early 中 108 例患者中的 56 例（52%）对“MTX+”表现出 IR。DAS28（调整后的 OR（OR）2.1，95%CI 1.4 至 3.2）、当前吸烟（OR 3.02，95%CI 1.1 至 8.0）和饮酒（OR 0.4，95%CI 0.1 至 0.9）被确定为基线预测因素。预测模型的接收者操作特征曲线下面积（AUROC）为 0.75（95%CI 0.66 至 0.84）；阳性（PPV）和阴性预测值（NPV）分别为 65%和 80%。当将该模型应用于验证队列时，AUROC 略有下降至 0.67（95%CI 0.55 至 0.79），PPV 和 NPV 分别下降至 54%和 80%。
较高的 DAS28、当前吸烟和不饮酒是 DMARD 初治新发 RA 患者对“MTX+”升级治疗反应不足的预测因素。
NCT01034137；结果公布后，ISRCTN26791028；结果公布后。
