Kristian Stengaard-Pedersen

Plasma MicroRNA profiles in patients with early rheumatoid arthritis responding to adalimumab plus methotrexate vs methotrexate alone: A placebo-controlled clinical trial

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Jacob Sode, Statens Serum Institut
  • ,
  • Sophine B. Krintel, Frederiksberg Hospital
  • ,
  • Anting Liu Carlsen, Syddansk Universitet
  • ,
  • Merete L. Hetland, Rigshospitalet
  • ,
  • Julia S. Johansen, Københavns Universitet, Rigshospitalet
  • ,
  • Kim HØrslev-Petersen, Gentofte Hospital, University of Copenhagen, Faculty of Health Sciences
  • ,
  • Kristian Stengaard-Pedersen
  • Torkell Ellingsen
  • ,
  • Mark Burton, Odense Universitetshospital
  • ,
  • Peter Junker, Odense Universitetshospital, Syddansk Universitet
  • ,
  • Mikkel Østergaard, Rigshospitalet
  • ,
  • Niels H.H. Heegaard, Odense Universitetshospital

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.

Original languageEnglish
JournalJournal of Rheumatology
Volume45
Issue1
Pages (from-to)53-61
Number of pages9
ISSN0315-162X
DOIs
Publication statusPublished - Jan 2018

    Research areas

  • Biological markers, Plasma micro-RNA, Rheumatoid arthritis

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