Mount Sinai School of Medicine, New York, NY, U.S.A.
Br J Dermatol. 2010 Jan;162(1):137-46. doi: 10.1111/j.1365-2133.2009.09491.x. Epub 2009 Nov 9.
Background PHOENIX 1 was a phase III, randomized, double-blind, placebo-controlled study that demonstrated the long-term efficacy and safety of ustekinumab in patients with moderate-to-severe psoriasis. Objectives To assess the effect of ustekinumab maintenance therapy on health-related quality of life (HRQoL) in PHOENIX 1 patients. Patients and methods Patients (n = 766) were randomized to receive ustekinumab 45 mg (n = 255) or 90 mg (n = 256) at weeks 0 and 4 and every 12 weeks thereafter, or placebo (n = 255) at weeks 0 and 4 with crossover to ustekinumab at week 12. Ustekinumab-randomized patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI) 75 at weeks 28 and 40 were re-randomized at week 40 to continue ustekinumab or be withdrawn until loss of therapeutic effect. HRQoL was assessed using the SF-36 and Dermatology Life Quality Index (DLQI). Results At baseline, more than 97% had a DLQI > 1 and the average DLQI was > 10, indicating a significant impact on patients' HRQoL. Significantly greater proportions of patients receiving ustekinumab 45 and 90 mg achieved a normalized DLQI score (< or = 1) compared with placebo (53.2%, 52.4% and 6.0%, respectively, both P < 0.001) at week 12 and achieved a clinically meaningful improvement (increase of at least five points) in SF-36 physical (23.1%, 33.7% and 15.6%) and mental (25.5%, 31.3% and 14.8%) component summary scores. At week 12, changes in individual DLQI and SF-36 domains were significantly better in each ustekinumab group vs. placebo (P < 0.001). The magnitude of improvement across SF-36 scales was greatest for the bodily pain and social functioning domains. Improvements in HRQoL were sustained with maintenance ustekinumab therapy through at least 1 year. Regression analysis showed that, after adjustment for improvement in PASI or Physician's Global Assessment (PGA), ustekinumab-treated patients demonstrated significant improvements in DLQI. Conclusions Ustekinumab improves HRQoL in patients with moderate-to-severe psoriasis. Patient-reported outcomes measured a treatment effect beyond that indicated by clinical measures.
PHOENIX 1 是一项 III 期、随机、双盲、安慰剂对照研究，证明了乌司奴单抗在中重度银屑病患者中的长期疗效和安全性。目的：评估乌司奴单抗维持治疗对 PHOENIX 1 患者健康相关生活质量（HRQoL）的影响。方法：患者（n = 766）按 2:2:1 的比例随机接受乌司奴单抗 45 mg（n = 255）、90 mg（n = 256）或安慰剂（n = 255）治疗，在第 0 和 4 周时给药，此后每 12 周给药 1 次，接受安慰剂治疗的患者在第 12 周时交叉至乌司奴单抗治疗。在第 28 和 40 周时达到银屑病面积和严重程度指数（PASI）75 改善≥75%的乌司奴单抗治疗患者在第 40 周时再次随机分组，继续接受乌司奴单抗治疗或停药直至治疗效果丧失。采用 SF-36 和皮肤病生活质量指数（DLQI）评估 HRQoL。结果：基线时，超过 97%的患者 DLQI > 1，平均 DLQI > 10，表明对患者 HRQoL 有显著影响。与安慰剂组相比，接受乌司奴单抗 45 和 90 mg 治疗的患者在第 12 周时达到正常 DLQI 评分（<或= 1）的比例显著更高（分别为 53.2%、52.4%和 6.0%，均 P < 0.001），在 SF-36 躯体（23.1%、33.7%和 15.6%）和精神（25.5%、31.3%和 14.8%）成分总分中实现了有临床意义的改善（至少提高 5 分）。在第 12 周时，与安慰剂组相比，乌司奴单抗治疗组的每个 DLQI 和 SF-36 域的变化均显著更好（P < 0.001）。SF-36 各量表的改善幅度最大的是躯体疼痛和社会功能域。接受乌司奴单抗维持治疗至少 1 年可维持 HRQoL 的改善。回归分析显示，在调整 PASI 或医生总体评估（PGA）的改善后，乌司奴单抗治疗的患者在 DLQI 方面显示出显著的改善。结论：乌司奴单抗可改善中重度银屑病患者的 HRQoL。患者报告的结局测量到的治疗效果超出了临床指标所指示的效果。
