Division of Dermatology, NorthShore University HealthSystem and University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60077, USA.
J Invest Dermatol. 2012 Feb;132(2):304-14. doi: 10.1038/jid.2011.304. Epub 2011 Oct 20.
A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to briakinumab (200 mg at weeks 0 and 4 and 100 mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 (P<0.001 each). At week 52, 79.2% of q4-wk-treated patients achieved PGA "clear/minimal" compared with 41.6% and 6.0% of q12-wk and placebo-treated patients, respectively (P<0.001 for all treatment comparisons). Higher numbers of the following adverse events (AEs) of interest were observed with briakinumab during the placebo-controlled period, suggesting the need for surveillance for these events: serious infections (five vs. one event with briakinumab vs. placebo, respectively), nonmelanoma skin cancers (NMSCs; four vs. zero squamous cell carcinomas (SCCs)), and major adverse cardiovascular events (MACEs; five vs. zero events).
一项先前的 II 期临床试验表明，完全人源抗白细胞介素 12/23 mAb 布利昔单抗在中重度银屑病中有效。随后进行了一项为期 52 周、双盲、安慰剂对照的 III 期研究，评估诱导和维持治疗。患者以 2:1 的比例随机分配至布利昔单抗（第 0 周和第 4 周及第 8 周 200mg，第 12 周 100mg）或安慰剂；第 12 周时医生总体评估为“清除”或“最小”（PGA“清除/最小”）的患者随后以 2:2:1 的比例再次随机分配至布利昔单抗 100mg 每 4 周（q4-wk）、每 12 周（q12-wk）或匹配安慰剂至第 52 周。主要分析采用无应答者推断比较实现 PGA“清除/最小”（第 12 周和第 52 周）和银屑病面积和严重程度指数（PASI 75；第 12 周）改善≥75%的比例。共有 76.0%的布利昔单抗治疗患者和 4.3%的安慰剂治疗患者实现了 PGA“清除/最小”，分别有 80.7%和 4.5%的患者实现了 PASI 75（P<0.001）。第 52 周时，q4-wk 治疗组有 79.2%的患者实现了 PGA“清除/最小”，而 q12-wk 组和安慰剂组分别有 41.6%和 6.0%的患者实现了这一目标（所有治疗组比较均 P<0.001）。在安慰剂对照期间，观察到布利昔单抗治疗组有更多以下感兴趣的不良事件（AE），这表明需要监测这些事件：严重感染（布利昔单抗组有 5 例，安慰剂组有 1 例）、非黑色素瘤皮肤癌（NMSC；布利昔单抗组有 4 例，安慰剂组有 0 例鳞状细胞癌（SCC））和主要不良心血管事件（MACE；布利昔单抗组有 5 例，安慰剂组有 0 例）。
