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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
- 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.
- Subjects :
- 0301 basic medicine
Adult
Male
medicine.medical_specialty
Immunology
Placebo
Gastroenterology
Arthritis, Rheumatoid
03 medical and health sciences
Young Adult
Rheumatology
Double-Blind Method
Internal medicine
medicine
Adalimumab
Immunology and Allergy
Humans
Prospective Studies
Plasma micro-RNA
Rheumatoid arthritis
Aged
Biological markers
Receiver operating characteristic
business.industry
Remission Induction
Middle Aged
medicine.disease
Clinical trial
MicroRNAs
030104 developmental biology
Logistic Models
Methotrexate
Treatment Outcome
ROC Curve
Antirheumatic Agents
Multivariate Analysis
Linear Models
Drug Therapy, Combination
Female
business
Rheumatism
Biomarkers
medicine.drug
Subjects
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