TY - JOUR
T1 - Prediction of treatment response to adalimumab
T2 - a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis
AU - Krintel, Sophine Boysen
AU - Dehlendorff, C
AU - Hetland, Merete Lund
AU - Hørslev-Petersen, K
AU - Andersen, K K
AU - Junker, P
AU - Pødenphanth, Jan
AU - Ellingsen, T
AU - Ahlquist, P
AU - Lindegaard, H M
AU - Linauskas, A
AU - Schlemmer, A
AU - Dam, M Y
AU - Hansen, I
AU - Horn, H C
AU - Jørgensen, A
AU - Raun, J
AU - Ammitzbøll, C G
AU - Østergaard, M
AU - Stengaard-Pedersen, K
AU - Johansen, Julia Sidenius
PY - 2016
Y1 - 2016
N2 - 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.The Pharmacogenomics Journal advance online publication, 5 May 2015; doi:10.1038/tpj.2015.30.
AB - 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.The Pharmacogenomics Journal advance online publication, 5 May 2015; doi:10.1038/tpj.2015.30.
U2 - 10.1038/tpj.2015.30
DO - 10.1038/tpj.2015.30
M3 - Journal article
C2 - 25939484
SN - 1470-269X
VL - 16
SP - 141
EP - 146
JO - The pharmacogenomics journal
JF - The pharmacogenomics journal
IS - 2
ER -