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Plasma MicroRNA Profiles in Patients with Early Rheumatoid Arthritis Responding to Adalimumab plus Methotrexate vs Methotrexate Alone: A Placebo-controlled Clinical Trial

Authors :
Niels H. H. Heegaard
Julia S. Johansen
Peter Junker
Anting Liu Carlsen
Torkell Ellingsen
Mikkel Østergaard
Merete Lund Hetland
Mark Burton
Kristian Stengaard-Pedersen
Jacob Sode
Sophine B. Krintel
Kim Hørslev-Petersen
Source :
Sode, J, Krintel, S B, Carlsen, A L, Hetland, M L, Johansen, J S, Hørslev-Petersen, K, Stengaard-Pedersen, K, Ellingsen, T, Burton, M, Junker, P, Østergaard, M & Heegaard, N H H 2018, ' Plasma MicroRNA Profiles in Patients with Early Rheumatoid Arthritis Responding to Adalimumab plus Methotrexate vs Methotrexate Alone : A Placebo-controlled Clinical Trial ', Journal of Rheumatology, vol. 45, no. 1, pp. 53-61 . https://doi.org/10.3899/jrheum.170266, Sode, J, Krintel, S B, Carlsen, A L, Hetland, M L, Johansen, J S, HØrslev-Petersen, K, Stengaard-Pedersen, K, Ellingsen, T, Burton, M, Junker, P, Østergaard, M & Heegaard, N H H 2018, ' Plasma MicroRNA profiles in patients with early rheumatoid arthritis responding to adalimumab plus methotrexate vs methotrexate alone : A placebo-controlled clinical trial ', Journal of Rheumatology, vol. 45, no. 1, pp. 53-61 . https://doi.org/10.3899/jrheum.170266
Publication Year :
2017

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–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.

Details

ISSN :
0315162X and 00660647
Volume :
45
Issue :
1
Database :
OpenAIRE
Journal :
The Journal of rheumatology
Accession number :
edsair.doi.dedup.....0e0940ffd180a9ececbfbae29a6042da
Full Text :
https://doi.org/10.3899/jrheum.170266