Woo Jin-Hyun, Lee Hyun-Joo, Sung Il-Hoon, Kim Tae-Hwan
Division of Rheumatology, the Hospital for Rheumatic Diseases, The Institute of Rheumatism, Hanyang University, Seol, Korea.
J Rheumatol. 2007 Aug;34(8):1753-9. Epub 2007 Jun 15.
Tumor necrosis factor-alpha has a prominent role in the inflammatory process and bone resorption in patients with ankylosing spondylitis (AS). We evaluated the markers of clinical efficacy and bone biochemical changes in Korean patients with AS treated with etanercept therapy.
Serum samples from 26 patients receiving etanercept for refractory AS were obtained at baseline and 12 weeks after treatment. Clinical measures and serum levels of transforming growth factor-Beta (TGF-Beta), matrix metalloproteinase-3 (MMP-3), macrophage-colony stimulating factor (M-CSF), bone-specific alkaline phosphatase (BALP), osteocalcin, C-telopeptide (CTX), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were measured at each timepoint.
Significant improvement of the Bath AS Disease Activity Index (BASDAI) and Functional Index (BASFI) was achieved after 12 weeks (p < 0.001). ASsessments in Ankylosing Spondylitis Working Group (ASAS) 20 criteria were achieved by 22 patients (84.6%) after 12 weeks' treatment. ASAS 50 and 70 were achieved by 10 (38.5%) and 7 patients (26.9%). Serum levels of BALP and osteocalcin were significantly increased after 12 weeks of treatment (p < 0.05). Serum levels of CTX were not changed after treatment. Serum levels of TGF-Beta, MMP-3, and M-CSF were significantly decreased after 12 weeks of treatment (p < 0.05). Serum levels of OPG and RANKL were not changed. Change of MMP-3 had a high correlation coefficient with changes of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) upon etanercept treatment (CRP, r = 0.446, p = 0.022; ESR, r = 0.449, p = 0.021).
In patients with AS, etanercept therapy may be effective for reducing disease activity and improving bone biochemical markers. MMP-3 may be a useful biomarker for monitoring etanercept therapy.
肿瘤坏死因子-α在强直性脊柱炎(AS)患者的炎症过程和骨吸收中起重要作用。我们评估了接受依那西普治疗的韩国AS患者的临床疗效指标和骨生化变化。
收集26例接受依那西普治疗的难治性AS患者在基线和治疗12周后的血清样本。在每个时间点测量临床指标以及转化生长因子-β(TGF-β)、基质金属蛋白酶-3(MMP-3)、巨噬细胞集落刺激因子(M-CSF)、骨特异性碱性磷酸酶(BALP)、骨钙素、C-末端肽(CTX)、核因子-κB受体激活剂配体(RANKL)和骨保护素(OPG)的血清水平。
12周后,巴斯强直性脊柱炎疾病活动指数(BASDAI)和功能指数(BASFI)有显著改善(p<0.001)。12周治疗后,22例患者(84.6%)达到强直性脊柱炎工作组(ASAS)20标准。10例(38.5%)和7例(26.9%)患者分别达到ASAS 50和70标准。治疗12周后,BALP和骨钙素的血清水平显著升高(p<0.05)。治疗后CTX的血清水平未改变。治疗12周后,TGF-β、MMP-3和M-CSF的血清水平显著降低(p<0.05)。OPG和RANKL的血清水平未改变。依那西普治疗后,MMP-3的变化与C反应蛋白(CRP)和红细胞沉降率(ESR)的变化具有较高的相关系数(CRP,r=0.446,p=0.022;ESR,r=0.449,p=0.021)。
在AS患者中,依那西普治疗可能对降低疾病活动度和改善骨生化指标有效。MMP-3可能是监测依那西普治疗的有用生物标志物。