Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA.
Br J Dermatol. 2012 Apr;166(4):861-72. doi: 10.1111/j.1365-2133.2012.10901.x.
An unmet need remains for safe and effective long-term treatments of psoriasis.
To evaluate ustekinumab efficacy and safety for up to 3 years in the PHOENIX 1 trial.
Patients (n = 766) with moderate-to-severe psoriasis were randomized to ustekinumab 45 mg or 90 mg at weeks 0 and 4, and then every 12 weeks, or placebo at weeks 0 and 4, with crossover to ustekinumab at week 12. Ustekinumab responders [≥ 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at weeks 28 and 40] were re-randomized at week 40 to continue or withdraw from treatment until psoriasis recurrence. Partial responders (week 28: PASI 50-74; week 40: < PASI 75) switched to dosing every 8 weeks. Clinical efficacy was assessed by PASI, the Physician's Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI) measures.
Overall, 79·8% of the ustekinumab-treated patients remained in the study for 3 years. PASI 75 response rates (45 mg: 61·2%; 90 mg: 72·4%) at week 76 were maintained through year 3 (45 mg: 62·7%; 90 mg: 72·2%); PGA response was similarly durable. At year 3, 80·9% (45 mg) and 82·7% (90 mg) of week 40 responders continuing treatment every 12 weeks achieved a PASI 75 response, while 42·6% (45 mg) and 58·0% (90 mg) achieved a PASI 90 response. Among partial responders adjusted to dosing every 8 weeks, 50·9% (45 mg) and 52·0% (90 mg) had a PASI 75 response at year 3. DLQI responses paralleled the PASI responses. Through year 3, no dose response was observed in rates of adverse events (AEs), overall infections, serious AEs, or AEs leading to discontinuation; nor was there evidence of cumulative organ toxicity. CONCLUSIONS; Continuous, stable, maintenance dosing with ustekinumab was generally well tolerated and sustained durable efficacy for up to 3 years of treatment.
仍需要安全有效的长期治疗银屑病的方法。
评估乌司奴单抗在 PHOENIX 1 试验中的疗效和安全性，最长可达 3 年。
766 例中重度银屑病患者随机接受乌司奴单抗 45 mg 或 90 mg，每 12 周 1 次，或安慰剂，每 4 周 1 次，在第 12 周交叉至乌司奴单抗治疗。乌司奴单抗应答者（第 28 周和第 40 周时基于银屑病面积和严重程度指数（PASI 75）较基线至少改善 75%）在第 40 周时重新随机继续或停止治疗直至银屑病复发。部分应答者（第 28 周：PASI 50-74；第 40 周：<PASI 75）转换为每 8 周给药。通过 PASI、医生总体评估（PGA）和皮肤病生活质量指数（DLQI）评估临床疗效。
总体而言，79.8%的乌司奴单抗治疗患者在研究中持续 3 年。第 76 周时的 PASI 75 应答率（45 mg：61.2%；90 mg：72.4%）在第 3 年仍保持不变（45 mg：62.7%；90 mg：72.2%）；PGA 应答同样持久。第 3 年时，45 mg 组和 90 mg 组中第 40 周时每 12 周接受治疗的应答者继续治疗时，80.9%（45 mg）和 82.7%（90 mg）达到 PASI 75 应答，而 42.6%（45 mg）和 58.0%（90 mg）达到 PASI 90 应答。在调整为每 8 周给药的部分应答者中，45 mg 组和 90 mg 组在第 3 年时分别有 50.9%（45 mg）和 52.0%（90 mg）达到 PASI 75 应答。DLQI 应答与 PASI 应答一致。第 3 年时，不良事件（AE）、总体感染、严重 AE 或导致停药的 AE 发生率、累积器官毒性均无剂量反应。
乌司奴单抗持续、稳定、维持剂量治疗通常具有良好的耐受性，可在长达 3 年的治疗中持续获得持久疗效。
