Etanercept联合甲氨蝶呤对类风湿关节炎的疗效观察

Observation of efficacy of Etanercept combined with methotrexate against rheumatoid arthritis

目的：探讨生物制剂肿瘤坏死因子α（tumor necrosis factor α，TNFα）抑制剂（Etanercept）联合甲氨蝶呤（methotrexate, MTX）对类风湿关节炎（rheumatoid arthritis, RA）患者的治疗效果及对血清基质金属蛋白酶3 （ matrix metalloproteinase 3, MMP-3）和血清淀粉样蛋白A（serum amyloid A, SAA）的影响。方法：45例RA患者经过MTX或者MTX和TNFα抑制剂Etanercept联合治疗，采用ELISA方法检测治疗6个月前后血清中MMP-3和SAA的滴度，采用DAS28评分评价疾病活动度和治疗效果，并检测治疗前后患者的血沉、血清C反应蛋白、类风湿因子和抗环瓜氨酸多肽抗体等水平。结果：经6个月治疗，MTX和TNFα抑制剂Etanercept联合治疗组患者显著有效率（48.1%）明显高于MTX治疗组（27.8%）（P〈0.05）。2组患者MMP-3滴度在治疗后均有下降：联合治疗组由治疗前73.3（19.9-135.3）ng·mL^-1下降到40.7（6.7-127.9） ng·ml^-1；MTX组由治疗前75.9 （17.8-133.5） ng·ml^-1下降到48.1 （16.4-126.0） ng·ml^-1。而对45例患者综合分析发现MMP-3下降程度与治疗后DAS28评分呈负相关（r=-0.577，P〈0.01）。SAA在治疗前疾病活动时高滴度，治疗后明显下降与ESR，CRP和DAS28成正相关。2组治疗的不良反应发生率无显著性差异。结论：生物制剂Etanercept联合MTX治疗RA优于单药MTX治疗。

OBJECTIVE To investigate the efficacy of tumor necrosis factor a （TNFα） inhibitor Etanercept combined with methotrexate （MTX） in treatment against rheumatoid arthritis （RA）, and to evaluate its influence on serum matrix metallopro- teinase 3（MMP-3） and serum amyloid A （SAA）. METHODS A total of 45 RA patients were enrolled to receive two different treatments for 6 months, patients in one group received MTX and the other TNFα inhibitor Etanercept combined with MTX. Clinical response to the therapy was evaluated by DAS28. Serum MMP-3, SAA and the other laboratory variables including ESR, CRP and anti-CCP were assessed at baseline and after 6 months of treatment. RESULTS Patients with good response were more in group receiving Etanercept combined treatment （48.1%） than in group receiving MTX （27. 8%）, the difference was statistically significant （P〈0. 05）. The serum level of MMP 3 was decreased in both groups after 6 months of treatment.. MMP-3 was reduced from 7. 33（1.99 - 13. 53） ng·ml^-1 to 4. 07（0. 67 - 12. 79） ng·ml^-1 in combined treatment group and from 7. 59（1.78 - 13.35） ng·ml^-1 to 4. 81 （1.64 - 12. 60） ng·ml^-1 in MTX group. The reduction of MMP-3 was negatively correla- ted with DAS28 after treatment by analyzing all patients （r= - 0. 577, P〈0. 01）. SAA level was high when the disease was active, and decreased after treatment, which might be correlated with ESR, CRP and DAS28. The incidences of side effects showed no significant difference between MTX group and combined treatment group. CONCLUSION TNFα inhibitor Etaner- cept combining MTX is better than MTX alone against RA.