Brandt Jan, Khariouzov Andre, Listing Joachim, Haibel Hildrun, Sörensen Helmut, Rudwaleit Martin, Sieper Joachim, Braun Jurgen
Department of Gastroenterology/Rheumatology, Benjamin Franklin Hospital, Free University (FU) Berlin, Germany.
J Rheumatol. 2004 Mar;31(3):531-8.
Anti-tumor necrosis factor-a (TNF-alpha) therapy has been successfully used in patients with active ankylosing spondylitis (AS) and other subtypes of spondyloarthritis (SpA). Treatment options for patients with severe forms of undifferentiated spondyloarthritis (uSpA), a rather frequent SpA subset, are limited. In this open study we examined the efficacy of the TNF-alpha receptor fusion protein etanercept in patients with uSpA.
Ten patients classified to have uSpA according to modified European Spondylarthropathy Study Group criteria in a severe and active stage of disease were included in the study and received etanercept in a dosage of 25 mg two times a week for 12 weeks, followed by an observation period of 12 weeks. The following outcome variables were used: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Functional Index (BASFI), pain on a numerical rating scale, disability by the Funktionsfragebogen Hannover (FFbH), a validated questionnaire to assess functional disability, and quality of life (Medical Outcome Study Short Form-36, SF-36). The primary outcome variable was defined as >or= 50% improvement of the BASDAI.
Treatment with etanercept resulted in a >or= 50% regression of disease activity in 60% (95% CI 31-83%) of the patients. The mean BASDAI at baseline of 6.1 (range 3.7-9.2) dropped significantly to 3.5 at Week 12 (0.8-8.7; p = 0.01). Function, spinal pain, peripheral arthritis, enthesitis, quality of life, and acute phase reactants improved similarly. The FFbH improved from 62.8% to 69.7%. After cessation of anti-TNF therapy, 4 out of 8 patients relapsed after an average of 4.5 weeks (range 3-6). Two patients went into longstanding remission. No severe adverse events or major infections were observed.
This study strongly suggests that treatment with etanercept has short term efficacy in patients with active and severe uSpA. Since it is known that 30-50% of uSpA patients develop AS over time, it will be important to study whether this can be prevented by anti-TNF-alpha therapy.
抗肿瘤坏死因子-α（TNF-α）疗法已成功应用于活动性强直性脊柱炎（AS）患者及其他脊柱关节炎（SpA）亚型患者。未分化脊柱关节炎（uSpA）是一种较为常见的SpA亚型，针对病情严重的uSpA患者，治疗选择有限。在这项开放性研究中，我们检测了TNF-α受体融合蛋白依那西普对uSpA患者的疗效。
本研究纳入了10例根据改良欧洲脊柱关节病研究组标准分类为处于疾病重度活动期的uSpA患者，给予依那西普，剂量为25mg，每周2次，共12周，随后进入12周的观察期。采用以下结局变量：巴斯强直性脊柱炎疾病活动指数（BASDAI）、功能指数（BASFI）、数字评定量表疼痛评分、汉诺威功能问卷（FFbH）评估的残疾程度（FFbH是一种用于评估功能残疾的有效问卷）以及生活质量（医学结局研究简表-36，SF-36）。主要结局变量定义为BASDAI改善≥50%。
依那西普治疗使60%（95%可信区间31%-83%）的患者疾病活动度下降≥50%。基线时平均BASDAI为6.1（范围3.7-9.2），在第12周时显著降至3.5（0.8-8.7；p=0.01）。功能、脊柱疼痛、外周关节炎、附着点炎、生活质量和急性期反应物均有类似改善。FFbH从62.8%改善至69.7%。停用抗TNF治疗后，8例患者中有4例在平均4.5周（范围3-6周）后复发。2例患者进入长期缓解期。未观察到严重不良事件或重大感染。
本研究强烈提示，依那西普治疗对活动期和重度uSpA患者有短期疗效。由于已知30%-50%的uSpA患者随时间推移会发展为AS，研究抗TNF-α疗法是否能预防这一情况将很重要。
