Gorman Jennifer D, Sack Kenneth E, Davis John C
Division of Rheumatology, University of California, San Francisco 94143, USA.
N Engl J Med. 2002 May 2;346(18):1349-56. doi: 10.1056/NEJMoa012664.
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.
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 (< or =10 mg per day), and disease-modifying antirheumatic drugs at stable doses during the trial.
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.
Treatment with etanercept for four months resulted in rapid, significant, and sustained improvement in patients with ankylosing spondylitis.
强直性脊柱炎的有效治疗方法很少，该病会导致严重的发病率。由于肿瘤坏死因子α在脊柱关节炎中起核心作用，我们对重组人肿瘤坏死因子受体（p75）：Fc融合蛋白依那西普在强直性脊柱炎患者中进行了一项随机、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毫克）或安慰剂，为期4个月。主要终点是晨僵、脊柱疼痛、功能、患者对疾病活动的整体评估及关节肿胀等指标的综合改善情况。试验期间允许患者继续服用非甾体抗炎药、口服皮质类固醇（≤10毫克/天）及剂量稳定的改善病情抗风湿药。
依那西普治疗带来了显著且持续的改善。4个月时，依那西普组80%的患者有治疗反应，而安慰剂组为30%（P = 0.004）。依那西普组在包括晨僵、脊柱疼痛、功能、生活质量、附着点炎、胸廓扩张度、红细胞沉降率及C反应蛋白等各项疾病活动指标上相对于基线值的改善明显更大。纵向分析显示治疗反应迅速且未随时间减弱。依那西普耐受性良好，两组不良事件发生率无显著差异。
依那西普治疗4个月可使强直性脊柱炎患者迅速、显著且持续地改善。
