@article {Sode53, author = {Jacob Sode and Sophine B. Krintel and Anting Liu Carlsen and Merete L. Hetland and Julia S. Johansen and Kim H{\o}rslev-Petersen and Kristian Stengaard-Pedersen and Torkell Ellingsen and Mark Burton and Peter Junker and Mikkel {\O}stergaard and Niels H.H. Heegaard}, title = {Plasma MicroRNA Profiles in Patients with Early Rheumatoid Arthritis Responding to Adalimumab plus Methotrexate vs Methotrexate Alone: A Placebo-controlled Clinical Trial}, volume = {45}, number = {1}, pages = {53--61}, year = {2018}, doi = {10.3899/jrheum.170266}, publisher = {The Journal of Rheumatology}, abstract = {Objective. The aim was to identify plasma (i.e., cell-free) microRNA (miRNA) predicting antitumor necrosis and/or methotrexate (MTX) treatment response in patients enrolled in an investigator-initiated, prospective, double-blinded, placebo-controlled trial (The OPERA study, NCT00660647).Methods. We included 180 disease-modifying antirheumatic drug{\textendash}naive patients with early rheumatoid arthritis (RA) randomized to adalimumab (ADA; n = 89) or placebo (n = 91) in combination with MTX. Plasma samples before and 3 months after treatment initiation were analyzed for 91 specific miRNA by quantitative reverse transcriptase-polymerase chain reaction on microfluidic dynamic arrays. A linear mixed-effects model was used to test for associations between pretreatment miRNA and changes in miRNA expression and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean (28 joints) remission at 3 and 12 months, applying false discovery rate correction for multiple testing. Using leave-one-out cross validation, we built predictive multivariate miRNA models and estimated classification performances using receiver-operating characteristics (ROC) curves.Results. In the ADA group, a higher pretreatment level of miR-27a-3p was significantly associated with remission at 12 months. The level decreased in remitting patients between pretreatment and 3 months, and increased in nonremitting patients. No associations were found in the placebo group receiving only MTX. Two multivariate miRNA models were able to predict response to ADA treatment after 3 and 12 months, with 63\% and 82\% area under the ROC curves, respectively.Conclusion. We identified miR-27a-3p as a potential predictive biomarker of ACR/EULAR remission in patients with early RA treated with ADA in combination with MTX. We conclude that pretreatment plasma-miRNA profiles may be of predictive value, but the results need confirmation in independent cohorts.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/45/1/53}, eprint = {https://www.jrheum.org/content/45/1/53.full.pdf}, journal = {The Journal of Rheumatology} }