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
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.
Pharmacogenomics J. 2016 Apr;16(2):141-6. doi: 10.1038/tpj.2015.30. Epub 2015 May 5.
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.
至少30%的类风湿关节炎（RA）患者对生物制剂无反应，这凸显了预测性生物标志物的必要性。我们旨在确定在180例初治RA患者中预测阿达木单抗反应的微小RNA（miRNA），这些患者参与了早期RA患者优化治疗算法（OPERA）研究，这是一项由研究者发起的前瞻性、双盲、安慰剂对照研究。患者被随机分为皮下注射40mg阿达木单抗组（n = 89）或安慰剂-阿达木单抗组（n = 91），并联合甲氨蝶呤治疗。使用TaqMan Human MicroRNA LDA, A Card v2.0（应用生物系统公司）测定377种miRNA的表达。使用交互分析测试miRNA与治疗反应之间的关联。使用三种不同归一化方法且P值<0.05的miRNA被纳入多变量模型。经过向后剔除，miR-22低表达与miR-886.3p高表达的组合与欧洲抗风湿病联盟（EULAR）良好反应相关。需要进一步研究以评估这些miRNA作为预测性生物标志物的效用。
