Cuppen Bart V J, Rossato Marzia, Fritsch-Stork Ruth D E, Concepcion Arno N, Schenk Yolande, Bijlsma Johannes W J, Radstake Timothy R D J, Lafeber Floris P J G
Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Arthritis Res Ther. 2016 Aug 24;18(1):189. doi: 10.1186/s13075-016-1085-z.
In rheumatoid arthritis, prediction of response to TNF-alpha inhibitor (TNFi) treatment would be of clinical value. This study aims to discover miRNAs that predict response and aims to replicate results of two previous studies addressing this topic.
From the observational BiOCURA cohort, 40 adalimumab- (ADA) and 40 etanercept- (ETN) treated patients were selected to enter the discovery cohort and baseline serum profiling on 758 miRNAs was performed. The added value of univariately selected miRNAs (p < 0.05) over clinical parameters in prediction of response was determined by means of the area under the receiver operating characteristic curve (AUC-ROC). Validation was performed by TaqMan single qPCR assays in 40 new patients.
Expression of miR-99a and miR-143 predicted response to ADA, and miR-23a and miR-197 predicted response to ETN. The addition of miRNAs increased the AUC-ROC of a model containing only clinical parameters for ADA (0.75 to 0.97) and ETN (0.68 to 0.78). In validation, none of the selected miRNAs significantly predicted response. miR-23a was the only overlapping miRNA compared to the two previous studies, however inversely related with response in one of these studies. The reasons for the inability to replicate previously proposed miRNAs predicting response to TNFi and replicate those from the discovery cohort were investigated and discussed.
To date, no miRNA consistently predicting response to TNFi therapy in RA has been identified. Future studies on this topic should meet a minimum of standards in design that are addressed in this study, in order to increase the reproducibility.
在类风湿性关节炎中，预测对肿瘤坏死因子-α抑制剂（TNFi）治疗的反应具有临床价值。本研究旨在发现可预测反应的微小RNA（miRNA），并旨在重复之前两项针对该主题的研究结果。
从观察性BiOCURA队列中，选择40例接受阿达木单抗（ADA）治疗和40例接受依那西普（ETN）治疗的患者进入发现队列，并对758种miRNA进行基线血清分析。通过受试者工作特征曲线下面积（AUC-ROC）确定单变量选择的miRNA（p < 0.05）在预测反应方面相对于临床参数的附加值。在40例新患者中通过TaqMan单重定量PCR分析进行验证。
miR-99a和miR-143的表达预测了对ADA的反应，miR-23a和miR-197预测了对ETN的反应。添加miRNA增加了仅包含ADA（从0.75至0.97）和ETN（从0.68至0.78）临床参数的模型的AUC-ROC。在验证中，所选的miRNA均未显著预测反应。与之前的两项研究相比，miR-23a是唯一重叠的miRNA，然而在其中一项研究中与反应呈负相关。对无法重复先前提出的预测对TNFi反应的miRNA以及无法重复发现队列中的miRNA的原因进行了调查和讨论。
迄今为止，尚未鉴定出一致预测类风湿性关节炎中对TNFi治疗反应的miRNA。未来关于该主题的研究应符合本研究中提出的最低设计标准，以提高可重复性。
