古塞库单抗治疗乌司奴单抗应答不足的银屑病患者的疗效和安全性：随机、双盲、III 期 NAVIGATE 试验结果。
Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial.
机构信息
Department of Dermatology, Dalhousie University, Halifax, Nova Scotia, Canada.
Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan.
出版信息
Br J Dermatol. 2018 Jan;178(1):114-123. doi: 10.1111/bjd.15750. Epub 2017 Oct 10.
BACKGROUND
Guselkumab, an anti-interleukin-23 monoclonal antibody, has demonstrated significant efficacy in phase III psoriasis trials.
OBJECTIVES
To evaluate the efficacy and safety of guselkumab in patients with moderate-to-severe plaque psoriasis who had an inadequate response to ustekinumab.
METHODS
In this phase III, randomized, double-blind study, 871 patients received open-label ustekinumab (45 mg or 90 mg) at weeks 0 and 4. At week 16, 268 patients with an inadequate response to ustekinumab [Investigator's Global Assessment (IGA) ≥ 2] were randomized (double-blind) to guselkumab 100 mg or to continue ustekinumab; 585 of 871 patients (67%) with IGA 0/1 at week 16 continued open-label ustekinumab. The primary end point was the number of visits at which randomized patients achieved IGA 0/1 and at least a two-grade improvement (from week 16) from week 28 to week 40. Improvement ≥ 90% or 100% in Psoriasis Area and Severity Index (PASI 90/100) and Dermatology Life Quality Index (DLQI) of 0/1 were also assessed.
RESULTS
The mean number of visits at which patients achieved IGA 0/1 and at least a two-grade improvemen (week 28-40) was significantly greater in the guselkumab group vs. the randomized ustekinumab group (1·5 vs. 0·7; P < 0·001); greater proportions of patients in the guselkumab group achieved IGA 0/1 and at least a two-grade improvement at week 28 (31·1% vs. 14·3%; P = 0·001) and week 52 (36·3% vs. 17·3%; P < 0·001). Greater proportions of patients treated with guselkumab achieved PASI 90, PASI 100 and DLQI 0/1 at week 52. After week 16, 64·4% of patients in the guselkumab group and 55·6% in the ustekinumab group had at least one adverse event (AE); infections were the most frequent AE type. Overall, 6·7% (n = 9) of patients in the guselkumab group had at least one serious AE compared with 4·5% (n = 6) for the ustekinumab group.
CONCLUSIONS
Patients treated with ustekinumab who did not achieve an IGA of 0/1 by week 16 derived significant benefit from switching to guselkumab.
背景
古塞库单抗是一种抗白细胞介素-23 单克隆抗体，在 III 期银屑病试验中显示出显著的疗效。
目的
评估古塞库单抗在对乌司奴单抗应答不足的中重度斑块状银屑病患者中的疗效和安全性。
方法
在这项 III 期、随机、双盲研究中，871 名患者在第 0 周和第 4 周接受了乌司奴单抗（45mg 或 90mg）的开放性标签治疗。在第 16 周，对乌司奴单抗应答不足的 268 名患者[研究者全球评估（IGA）≥2]被随机（双盲）分配至古塞库单抗 100mg 或继续乌司奴单抗治疗；871 名患者中有 585 名（67%）在第 16 周 IGA 为 0/1，继续接受开放性标签乌司奴单抗治疗。主要终点是从第 28 周到第 40 周，随机患者达到 IGA 0/1 和至少两等级改善（从第 16 周开始）的访视点数量。银屑病面积和严重程度指数（PASI 90/100）和皮肤病生活质量指数（DLQI）改善≥90%或 100%为 0/1 也进行了评估。
结果
与随机乌司奴单抗组相比，古塞库单抗组达到 IGA 0/1 和至少两等级改善的访视点比例显著更高（第 28-40 周，1.5 比 0.7；P<0.001）；古塞库单抗组在第 28 周（31.1%比 14.3%；P=0.001）和第 52 周（36.3%比 17.3%；P<0.001）时达到 IGA 0/1 和至少两等级改善的患者比例更高。更多接受古塞库单抗治疗的患者在第 52 周时达到 PASI 90、PASI 100 和 DLQI 0/1。第 16 周后，古塞库单抗组 64.4%的患者和乌司奴单抗组 55.6%的患者至少发生了一次不良事件（AE）；感染是最常见的 AE 类型。总体而言，古塞库单抗组有 6.7%（n=9）的患者至少发生了一次严重 AE，而乌司奴单抗组为 4.5%（n=6）。
结论
在第 16 周时 IGA 未达到 0/1 的乌司奴单抗治疗患者，改用古塞库单抗可显著获益。
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