人重组白细胞介素-1受体拮抗剂在类风湿关节炎治疗中的继发性失效  

Secondary failure to treatment with recombinant human interleukin-1 receptor antagonist in Chinese patients with rheumatoid arthritis

作　　者：张清[1] 岳涛 周凌[1] 刘玮[1] 包军[1] 徐沪济[1] 

机构地区：[1]第二军医大学附属长征医院风湿免疫科,上海200003 [2]上海市光华中西医结合医院风湿科

出　　处：《中华风湿病学杂志》2012年第5期335-338,共4页Chinese Journal of Rheumatology

基　　金：基金项目：国家自然科学基金（81172782）;上海市自然科学基金（10ZR1422500）

摘　　要：目的观察人重组白细胞介素-1受体拮抗剂（IL-IRa）联合甲氨蝶呤治疗活动期类风湿关节炎（RA）患者的疗效。方法54例经甲氨蝶呤治疗至少12周以上的活动期RA患者，随机接受每日皮下注射IL-1Ra80mg或安慰剂，每4周进行随访，按照美国风湿病学会制订的疗效标准评估临床疗效，共24周。应用矿检验比较2治疗组间疗效达到ACR20、ACR50和ACR70的患者比例的差异。应用t检验（参数分析）或者秩和检验（非参数分析）比较2治疗组间基线值变量和28个关节的疾病活动指数（DAS28）的差异。结果在治疗第24周，IL-1Ra联合甲氨蝶呤治疗组中27例（64％）的患者疗效改善达到ACR20，显著高于安慰剂组2例（17％）（P=0．004）。IL-1Ra治疗组中，38％的患者疗效改善达到ACR50，17％达到ACR70；而安慰剂组中无一例达到ACR50或ACR70改善。然而，接受IL．1Ra治疗的42例患者中有9例在初始治疗时病情显著改善，但之后却出现疗效下降。结论IL，1Ra通过阻断IL-1，可有效改善活动期RA患者的临床表现。然而，大约1／5接受IL-1Ra治疗的患者发生继发性失效。Objective To assess the efficacy of interleukin （IL）-IRa, a recombinant human IL-1 receptor antagonist, plus methotrexate （MTX） in patients with active rheumatoid arthritis （RA） refractory to MTX therapy. Methods A total of 54 patients with active RA, who had been taking MTX at a stable dosage, were randomized to receive daily subcutaneous injections of IL-IRa （80 rag） or placebo. The proportion of patients who had a response as assessed by ACR20, ACR50 and ACR70 was analyzed using Chi-square test measures.Baseline variables and DAS28 were analyzed using Student＇s t-test （parametric） or Wilcoxon＇s rank sum test （nonparametric） as appropriate. Results After 24 weeks, more patients achieved clinical benefits treated with IL-1Ra plus MTX compared with MTX alone （64% vs 17%, P=0.004） as determined by the ACR20 improvement. In the IL-1Ra group, an ACR50 response was observed in 38% and an ACRT0 response in 17%. None of the patients treated with MTX alone achieved ACR50 or ACR 70 improvement. However, 9 of 42 （21%） patients in the IL-1Ra group, who showed therapeutic response initially, had secondary drug failure to IL-1Ra therapy thereafter. A significant increase in mean responders to IL-1Ra, compared with placebo. Conclusion DAS28 from baseline was found in the non- IL-1Ra is effective for the treatment of patients with active RA by blocking IL-1. However, the efficacy of IL-1Ra is lost soon in about one-fifth of patients in spite of initial good response.

关 键 词：关节炎 类风湿 药物疗法 联合 药物耐受性 白细胞介素1受体拮抗剂 

分 类 号：R593[医药卫生—内科学]