Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.
At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.
Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.|Department of Medicine, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.
S B
SB
Krintel
Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
C
C
Dehlendorff
Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
M L
ML
Hetland
King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Graasten, Denmark.
K
K
Hørslev-Petersen
Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
K K
KK
Andersen
Department of Rheumatology, Odense University Hospital, Odense, Denmark.
P
P
Junker
Department of Rheumatology, Copenhagen University Hospital at Gentofte, Copenhagen, Denmark.
J
J
Pødenphant
Diagnostic Centre, Regional Hospital Silkeborg, Silkeborg, Denmark.
T
T
Ellingsen
Department of Rheumatology, Vejle Hospital, Vejle, Denmark.
P
P
Ahlquist
Department of Rheumatology, Odense University Hospital, Odense, Denmark.
H M
HM
Lindegaard
Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark.
A
A
Linauskas
Department of Rheumatology, Aalborg Hospital, Aalborg, Denmark.
A
A
Schlemmer
Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
M Y
MY
Dam
Department of Rheumatology, Viborg Hospital, Viborg, Denmark.
I
I
Hansen
Department of Rheumatology, Vejle Hospital, Vejle, Denmark.
H C
HC
Horn
Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
A
A
Jørgensen
King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Graasten, Denmark.
J
J
Raun
Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
C G
CG
Ammitzbøll
Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
M
M
Østergaard
Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
K
K
Stengaard-Pedersen
Department of Medicine, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Oncology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.
J S
JS
Johansen
D000068879:Adalimumab / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; C548375:MIRN22 microRNA, human; C559060:MIRN886 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab