Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor α
Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor α
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DOI：
10.1056/nejmoa012664
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发表时间：
2002-05-02
影响因子：
158.5
通讯作者：
Davis, JC
中科院分区：
文献类型：
--
作者：
Gorman, JD;Sack, KE;Davis, JC
背景：强直性脊柱炎的发病率较高，但目前尚无有效的治疗方法。由于肿瘤坏死因子（α）在脊柱关节炎中的中心作用，我们对强直性脊柱炎患者进行了一项依那西普（一种重组人肿瘤坏死因子受体（p75）：Fc融合蛋白）的随机、双盲、安慰剂对照试验。40例活动性，炎性强直性脊柱炎患者被随机分配接受每周两次皮下注射依那西普（25 mg）或安慰剂，持续4个月。主要终点是晨僵、脊柱疼痛、功能、患者对疾病活动性的总体评估和关节肿胀的改善。患者被允许继续服用非甾体类抗风湿药物，口服皮质类固醇（小于或等于10毫克，每天），和疾病缓解抗风湿药物在稳定的剂量在trial.Results：治疗与依那西普导致显着和持续的改善。在四个月时，依那西普组80%的患者有治疗反应，而安慰剂组只有30%（P=0.004）。依那西普组疾病活动度的各种指标（包括晨僵、脊柱疼痛、功能、生活质量、附着点炎、胸部扩张、红细胞沉降率和C-反应蛋白）的基线值改善显著更大。纵向分析表明，治疗反应迅速，并没有随着时间的推移而减弱。依那西普耐受性良好，两组之间的不良事件发生率无显着差异。结论：治疗与依那西普四个月导致强直性脊柱炎患者快速，显着，持续改善。
Background: There are few effective treatments for ankylosing spondylitis, which causes substantial morbidity. Because of the central role of tumor necrosis factor (alpha) in the spondyloarthritides, we performed a randomized, double-blind, placebo-controlled trial of etanercept, a recombinant human tumor necrosis factor receptor (p75):Fc fusion protein, in patients with ankylosing spondylitis.Methods: Forty patients with active, inflammatory ankylosing spondylitis were randomly assigned to receive twice-weekly subcutaneous injections of etanercept (25 mg) or placebo for four months. The primary end point was a composite of improvements in measures of morning stiffness, spinal pain, functioning, the patient's global assessment of disease activity, and joint swelling. Patients were allowed to continue taking nonsteroidal antiinflammatory drugs, oral corticosteriods (less than or equal to10 mg per day), and disease-modifying antirheumatic drugs at stable doses during the trial.Results: Treatment with etanercept resulted in significant and sustained improvement. At four months, 80 percent of the patients in the etanercept group had a treatment response, as compared with 30 percent of those in the placebo group (P=0.004). Improvements over base-line values for various measures of disease activity, including morning stiffness, spinal pain, functioning, quality of life, enthesitis, chest expansion, erythrocyte sedimentation rate, and C-reactive protein, were significantly greater in the etanercept group. Longitudinal analysis showed that the treatment response was rapid and did not diminish over time. Etanercept was well tolerated, with no significant differences in rates of adverse events between the two groups.Conclusions: Treatment with etanercept for four months resulted in rapid, significant, and sustained improvement in patients with ankylosing spondylitis.