University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
N Engl J Med. 2010 Jan 14;362(2):118-28. doi: 10.1056/NEJMoa0810652.
Biologic agents offer a range of new therapeutic options for patients with psoriasis; however, the relative benefit-risk profiles of such therapies are not well known. We compared two biologic agents, ustekinumab (an interleukin-12 and interleukin-23 blocker) and etanercept (an inhibitor of tumor necrosis factor alpha), for the treatment of psoriasis.
We randomly assigned 903 patients with moderate-to-severe psoriasis to receive subcutaneous injections of either 45 or 90 mg of ustekinumab (at weeks 0 and 4) or high-dose etanercept (50 mg twice weekly for 12 weeks). The primary end point was the proportion of patients with at least 75% improvement in the psoriasis area-and-severity index (PASI) at week 12; a secondary end point was the proportion with cleared or minimal disease on the basis of the physician's global assessment. Assessors were unaware of the treatment assignments. The efficacy and safety of a crossover from etanercept to ustekinumab were evaluated after week 12.
There was at least 75% improvement in the PASI at week 12 in 67.5% of patients who received 45 mg of ustekinumab and 73.8% of patients who received 90 mg, as compared with 56.8% of those who received etanercept (P=0.01 and P<0.001, respectively). Similarly, 65.1% of patients who received 45 mg of ustekinumab and 70.6% of patients who received 90 mg of ustekinumab had cleared or minimal disease according to the physician's global assessment, as compared with 49.0% of those who received etanercept (P<0.001 for both comparisons). Among patients who did not have a response to etanercept, 48.9% had at least 75% improvement in the PASI within 12 weeks after crossover to ustekinumab. One or more adverse events occurred through week 12 in 66.0% of patients who received 45 mg of ustekinumab and 69.2% of patients who received 90 mg of ustekinumab and in 70.0% who received etanercept; 1.9%, 1.2%, and 1.2%, respectively, had serious adverse events. Safety patterns were similar before and after crossover from etanercept to ustekinumab.
The efficacy of ustekinumab at a dose of 45 or 90 mg was superior to that of high-dose etanercept over a 12-week period in patients with psoriasis. (ClinicalTrials.gov number, NCT00454584.)
生物制剂为中重度银屑病患者提供了一系列新的治疗选择，但这些治疗方法的相对获益风险尚不清楚。我们比较了两种生物制剂，乌司奴单抗（一种白细胞介素-12 和白细胞介素-23 抑制剂）和依那西普（一种肿瘤坏死因子-α 抑制剂），用于治疗银屑病。
我们将 903 名中重度银屑病患者随机分为两组，分别接受 45 或 90 mg 乌司奴单抗（第 0 周和第 4 周）或高剂量依那西普（每周 2 次，每次 50 mg，共 12 周）皮下注射。主要终点是治疗 12 周后 PASI 至少改善 75%的患者比例；次要终点是根据医生的总体评估，清除或最小疾病的患者比例。评估者不知道治疗分配。在第 12 周后评估了依那西普交叉至乌司奴单抗的疗效和安全性。
接受 45 mg 乌司奴单抗治疗的患者中至少有 75%的 PASI 在第 12 周改善，接受 90 mg 乌司奴单抗治疗的患者中至少有 73.8%的 PASI 改善，而接受依那西普治疗的患者中仅有 56.8%（P=0.01 和 P<0.001）。同样，接受 45 mg 乌司奴单抗治疗的患者中 65.1%和接受 90 mg 乌司奴单抗治疗的患者中 70.6%的患者根据医生的总体评估达到清除或最小疾病，而接受依那西普治疗的患者中仅有 49.0%（两者比较均 P<0.001）。在对依那西普无反应的患者中，有 48.9%的患者在交叉至乌司奴单抗后 12 周内 PASI 至少改善 75%。接受 45 mg 乌司奴单抗治疗的患者中 66.0%和接受 90 mg 乌司奴单抗治疗的患者中 69.2%以及接受依那西普治疗的患者中 70.0%在第 12 周前出现 1 次或多次不良事件；分别有 1.9%、1.2%和 1.2%的患者发生严重不良事件。依那西普交叉至乌司奴单抗前后的安全性模式相似。
在 12 周内，乌司奴单抗的疗效优于高剂量依那西普，剂量为 45 或 90 mg，用于治疗银屑病患者。（临床试验.gov 编号，NCT00454584）
