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

• Published in: The pharmacogenomics journal Vol. 16; no. 2; pp. 141 - 146
• Main Authors: Krintel, S B, Dehlendorff, C, Hetland, M L, Hørslev-Petersen, K, Andersen, K K, Junker, P, Pødenphant, J, Ellingsen, T, Ahlquist, P, Lindegaard, H M, Linauskas, A, Schlemmer, A, Dam, M Y, Hansen, I, Horn, H C, Jørgensen, A, Raun, J, Ammitzbøll, C G, Østergaard, M, Stengaard-Pedersen, K, Johansen, J S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2016; Nature Publishing Group
• Subjects: 45/77; 692/53/2423; Adalimumab; Adalimumab - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Biomarkers; Biomedical and Life Sciences; Biomedicine; Double-Blind Method; Double-blind studies; Drug metabolism; Drug therapy; Female; Gene Expression; Genetic aspects; Human Genetics; Humans; Male; Methotrexate; MicroRNAs; MicroRNAs - blood; Middle Aged; miRNA; Monoclonal antibodies; Oncology; original-article; Patient outcomes; Patients; Pharmacotherapy; Placebos; Prospective Studies; Psychopharmacology; Rheumatoid arthritis; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2015.30

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.