一项随机、双盲、安慰剂对照研究，旨在评估甲氨蝶呤联合依那西普治疗中重度斑块状银屑病的疗效。

BACKGROUND

Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis.

OBJECTIVES

To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy.

METHODS

Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5-15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24.

RESULTS

In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician's Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm.

CONCLUSIONS

Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.

背景

依那西普联合甲氨蝶呤治疗银屑病尚未得到充分研究。

目的

评估依那西普联合甲氨蝶呤与依那西普单药治疗中重度斑块状银屑病患者的疗效，这些患者之前未接受过甲氨蝶呤或肿瘤坏死因子抑制剂治疗。

方法

患者接受依那西普每周两次 50mg 治疗 12 周，随后每周一次 50mg 治疗 12 周，随机 1:1 接受甲氨蝶呤（每周 7.5-15mg）或安慰剂。主要终点是第 24 周时达到银屑病面积和严重程度指数（PASI 75）改善≥75%的患者比例。

结果

每组共有 239 名患者入组。第 24 周时，联合治疗组的 PASI 75 显著高于单药治疗组（77.3% vs. 60.3%；P < 0.0001）。第 12 周时其他 PASI 改善评分[PASI 75，70.2% vs. 54.3%（P = 0.01）；PASI 50，92.4% vs. 83.8%（P = 0.01）；PASI 90，34.0% vs. 23.1%（P = 0.03）]也显示出类似的结果，第 24 周时 PASI 50（91.6% vs. 84.6%；P = 0.01）和 PASI 90（53.8% vs. 34.2%；P = 0.01）也显示出类似的结果。接受联合治疗的患者比接受单药治疗的患者有更多的静态医生整体评估为清除/几乎清除，第 12 周时为 65.5% vs. 47.0%（P = 0.01），第 24 周时为 71.8% vs. 54.3%（P = 0.01）。联合治疗组和单药治疗组分别有 74.9%和 59.8%的患者报告了不良事件（AE），每组均有 3 例严重 AE。