Haibel Hildrun, Rudwaleit Martin, Listing Joachim, Heldmann Frank, Wong Robert L, Kupper Hartmut, Braun Jürgen, Sieper Joachim
Charité Medical University Hospital, Campus Benjamin Franklin, Berlin, Germany.
Arthritis Rheum. 2008 Jul;58(7):1981-91. doi: 10.1002/art.23606.
To evaluate the efficacy and safety of the tumor necrosis factor (TNF) antagonist adalimumab in patients with axial spondylarthritis (SpA) without radiographically defined sacroiliitis refractory to conventional treatment.
Patients with active axial SpA (n = 46) were randomized to receive placebo or adalimumab at a dosage of 40 mg subcutaneously every other week for 12 weeks, followed by an open-label extension that continued up to week 52. The diagnosis of axial SpA required the presence of 3 of 6 diagnostic criteria, including 2 of the following 3 criteria: inflammatory back pain, HLA-B27 positivity, or acute inflammation of the spine or sacroiliac joints on magnetic resonance imaging, in the absence of radiographic evidence of sacroiliitis. The primary end point was a 40% response according to the improvement criteria of the Assessment of SpondyloArthritis international Society (ASAS40).
All 46 patients (22 receiving adalimumab and 24 receiving placebo) completed the 12-week trial; 38 patients completed the extension period to week 52. At week 12, an ASAS40 response was achieved by 54.5% of the adalimumab-treated patients, as compared with 12.5% of the placebo-treated patients (P = 0.004). After switching to adalimumab, a similar degree of efficacy was also achieved by the patients who were initially treated with placebo. Efficacy was maintained in all patients until week 52. Young age at study entry and an elevated C-reactive protein concentration were the best predictors of achieving an ASAS40 response. Serious adverse events occurred in 5 patients, none of which was related to the study drug.
Adalimumab is the first TNF antagonist to demonstrate good clinical efficacy and safety in patients with axial SpA without radiographically defined sacroiliitis.
评估肿瘤坏死因子（TNF）拮抗剂阿达木单抗在传统治疗无效且无影像学确诊骶髂关节炎的中轴型脊柱关节炎（SpA）患者中的疗效和安全性。
46例活动性中轴型SpA患者被随机分为两组，一组接受安慰剂治疗，另一组接受皮下注射剂量为40mg、每两周一次的阿达木单抗治疗，为期12周，随后进入开放标签扩展期，持续至第52周。中轴型SpA的诊断需要满足6项诊断标准中的3项，包括以下3项标准中的2项：炎性背痛、HLA-B27阳性或磁共振成像显示脊柱或骶髂关节急性炎症，且无骶髂关节炎的影像学证据。主要终点是根据国际脊柱关节炎评估协会（ASAS40）改善标准达到40%的缓解率。
46例患者（22例接受阿达木单抗治疗和24例接受安慰剂治疗）均完成了12周的试验；38例患者完成了至第52周的扩展期。在第12周时，接受阿达木单抗治疗的患者中有54.5%达到ASAS40缓解，而接受安慰剂治疗的患者中这一比例为12.5%（P = 0.004）。最初接受安慰剂治疗的患者改用阿达木单抗后，也取得了相似程度的疗效。所有患者的疗效一直维持到第52周。研究开始时年龄较小和C反应蛋白浓度升高是达到ASAS40缓解的最佳预测指标。5例患者发生了严重不良事件，均与研究药物无关。
阿达木单抗是首个在无影像学确诊骶髂关节炎的中轴型SpA患者中显示出良好临床疗效和安全性的TNF拮抗剂。
