来氟米特治疗强直性脊柱炎的随机双盲安慰剂对照临床试验

Leflunomide in treatment of ankylosing spondylitis:a double-blind,rando-mized,placebo-controlled clinical trial

目的探讨来氟米特治疗强直性脊柱炎(AS)的疗效和安全性。方法用随机、双盲、安慰剂对照的临床研究方法,将60例(其中29例伴周围关节炎)经柳氮磺吡啶和非甾体抗炎药治疗无效的活动性AS患者按2∶1的比例随机分为试验组(40例)和对照组(20例),分别口服来氟米特20 mg,qd和安慰剂,疗程12 wk,观察疗效和不良反应。结果治疗12 wk时试验组ASAS20有效率为39%,显著高于对照组(5%,P<0.01)。试验组中有周围关节炎AS与无周围关节炎AS比较,C反应蛋白、压痛周围关节数、肿胀周围关节数、Bath强直性脊柱炎患者整体评分、Bath强直性脊柱炎功能指数、Bath强直性脊柱炎疾病活动指数、医生和患者对疾病活动性的整体评价等指标有显著改善(均P<0.05),显著提高ASAS20有效率(P<0.05)。不良反应发生率在试验组与对照组间无显著差异(P>0.05)。结论来氟米特治疗伴有周围关节炎的AS安全有效。

AIM To evaluate the efficacy and safety of leflunomide （LFM） in the treatment of active ankylosing spondylitis （AS）. METHODS Sixty active AS patients, who were refractory to the treatment of sulfasalazine （SSZ） and non-steroidal anti-inflammatory drugs （NSAIDs） , were randomized at baseline to receive either LFM 20 mg, qd （trial group, n = 40） or matching placebo （control group, n = 20） for 12 weeks. For analysis of LFM effects on AS with peripheral arthritis （PA）, 29 AS patients with PA were involved in the 60 eligible patients. Both the therapeutic effects and adverse reactions were observed during the study period. RESULTS Effective rate in the trial group （39%） was higher （P 〈 0.01 ） than that in the control group （5%）. Compared with AS patients without PA, LFM significantly improved the following indexes in AS patients with PA： C-reactive protein, tenderness in the peripheral joints, swelling in the peripheral joints, Bath ankylosing spondylitis patient global score （BAS-G）, Bath ankylosing spondylitis functional index （BASFI）, Bath ankylosing spon-dylitis disease activity index （BASDAI）, patient＇s and physician＇s global assessment of disease activity, and the rate of ASAS 20% responders （P 〈 0.05）. The indexes reflecting the lesions of axial joints, including linear definition of the Bath ankylosing spondylitis metrology index （BASMI^n）, chest expansion, total pain in the spine and night pain in the spine, were not ameliorated in the patients with PA. There were no significant differences in adverse reaction between two groups （P 〉 0.05）. CONCLUSION LFM is effective and safe in the treatment of AS with PA, even these patients are refractory to SSZ and NSAIDs.