Wang Xuetong, Ma Cuili, Li Ping, Zhao Feng, Bi Liqi
Department of Rheumatology and Immunology, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, 130033, China.
Clin Rheumatol. 2017 Jun;36(6):1369-1377. doi: 10.1007/s10067-017-3668-8. Epub 2017 May 4.
This study aims to investigate the effect of iguratimod, a novel disease-modifying antirheumatic drug, alone or combined with methotrexate (MTX), on the serum levels of regulators of bone remodeling (receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and Dickkopf-1 (DKK-1)) and bone remodeling markers (C-telopeptide of type I collagen (CTX-I) and procollagen type I N-terminal propeptide (PINP)) in patients with rheumatoid arthritis (RA). Patients with RA were treated with iguratimod, MTX, or their combination for 12 months. Serum samples were collected before treatment and 6 and 12 months afterwards. RANKL, OPG, DKK-1, CTX-I, and PINP levels were measured, and radiographic progression was assessed. The serum RANKL levels decreased after treatment for 6 and 12 months with iguratimod (median: baseline 565.00 pmol/L vs. 6 months 411.00 pmol/L vs. 12 months 212.00 pmol/L), MTX (median: baseline 562.50 pmol/L vs. 6 months 399.50 pmol/L vs. 12 months 163.50 pmol/L), and their combination (median: baseline 971.00 pmol/L vs. 6 months 272.50 pmol/L vs. 12 months 241.50 pmol/L). Combination therapy showed greater effects 6 months post-treatment compared to single-drug therapy. PINP levels increased significantly 12 months post-treatment with all therapies, but only the combination therapy led to decreased CTX-I levels. OPG and DKK-1 levels showed no significant changes. The three treatments showed no significant differences in radiographic progression. Iguratimod could stimulate bone formation and regulate the RANKL/RANK/OPG system rather than DKK-1levels. Its effects are comparable to those of MTX, and combination therapy showed stronger effects.
本研究旨在调查新型抗风湿药物艾拉莫德单独或联合甲氨蝶呤（MTX）对类风湿关节炎（RA）患者血清骨重塑调节因子（核因子κB受体活化因子配体（RANKL）、骨保护素（OPG）和Dickkopf-1（DKK-1））水平及骨重塑标志物（I型胶原C端肽（CTX-I）和I型前胶原N端前肽（PINP））的影响。RA患者接受艾拉莫德、MTX或二者联合治疗12个月。在治疗前以及治疗后6个月和12个月采集血清样本。检测RANKL、OPG、DKK-1、CTX-I和PINP水平，并评估影像学进展。使用艾拉莫德治疗6个月和12个月后血清RANKL水平降低（中位数：基线565.00 pmol/L vs. 6个月411.00 pmol/L vs. 12个月212.00 pmol/L），MTX治疗后（中位数：基线562.50 pmol/L vs. 6个月399.50 pmol/L vs. 12个月163.50 pmol/L），以及二者联合治疗后（中位数：基线971.00 pmol/L vs. 6个月272.50 pmol/L vs. 12个月241.50 pmol/L）。与单药治疗相比，联合治疗在治疗后6个月显示出更大效果。所有治疗在治疗后12个月时PINP水平均显著升高，但只有联合治疗导致CTX-I水平降低。OPG和DKK-1水平无显著变化。三种治疗在影像学进展方面无显著差异。艾拉莫德可刺激骨形成并调节RANKL/RANK/OPG系统，而非DKK-1水平。其效果与MTX相当，联合治疗效果更强。
