Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis

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 B

AU - Dehlendorff, C

AU - Hetland, M L

AU - Hørslev-Petersen, K

AU - Andersen, K K

AU - Junker, P

AU - Pødenphant, 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, Mikkel

AU - Stengaard-Pedersen, K

AU - Johansen, J S

PY - 2016/4/1

Y1 - 2016/4/1

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.

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.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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 - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

IS - 2

ER -