BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.