Background

Antibodies targeting interleukin (IL)-23 and IL-17A effectively treat moderate-to-severe psoriasis. ECLIPSE is the first comparator study of an IL-23p19 inhibitor, guselkumab, versus an IL-17A inhibitor, secukinumab. The primary objective of this study was to show superiority of clinical response at week 48 for guselkumab versus secukinumab.

Methods

In this phase 3, multicentre, double-blind, randomised, comparator-controlled trial at 142 outpatient clinical sites in nine countries (Australia, Canada, Czech Republic, France, Germany, Hungary, Poland, Spain, and the USA), eligible patients were aged 18 years or older, had moderate-to-severe plaque-type psoriasis, and were candidates for phototherapy or systemic therapy. Eligible patients were randomly assigned with permuted block randomisation using an interactive web response system to receive either guselkumab (100 mg at weeks 0 and 4 then every 8 weeks) or secukinumab (300 mg at weeks 0, 1, 2, 3, and 4, and then every 4 weeks). The primary endpoint, the proportion of patients in the intention-to-treat population who achieved 90% reduction or more from baseline of Psoriasis Area and Severity Index (PASI 90 response) at week 48, and major secondary endpoints (the proportions of patients in the guselkumab group and in the secukinumab group who achieved a PASI 75 response at both weeks 12 and 48, a PASI 90 response at week 12, a PASI 75 response at week 12, a PASI 100 response at week 48, an Investigator's Global Assessment [IGA] score of 0 [cleared] at week 48, and an IGA score of 0 or 1 [minimal] at week 48) were to be tested in a fixed sequence to control type I error rate. Safety was evaluated in patients who received one or more doses of study drug from week 0 to 56. The study is registered with , .

Findings

This study was done between April 27, 2017, and Sept 20, 2018. 1048 eligible patients were enrolled and, of these, 534 were assigned to receive guselkumab and 514 to receive secukinumab. The proportion of patients with a PASI 90 response at week 48 was greater in the guselkumab group (451 [84%]) than in the secukinumab group (360 [70%]; p<0·0001). Although non-inferiority (margin of 10 percentage points) was established for the first major secondary endpoint (452 [85%] of patients in the guselkumab group vs 412 [80%] of patients in the secukinumab group achieving a PASI 75 response at both weeks 12 and 48), superiority was not established (p=0·0616). Consequently, formal statistical testing was not done for subsequent major secondary endpoints. Proportions of patients with adverse events, infections, and serious adverse events were similar between the two treatments and, in general, safety findings were consistent with registrational trial observations.

Interpretation

Guselkumab showed superior long-term efficacy based on PASI 90 at week 48 when compared with secukinumab for treating moderate-to-severe psoriasis. This finding could assist health-care providers in their decision making process when selecting a biologic for treating moderate-to-severe psoriasis.

Funding

This study was funded by Janssen Research & Development.

中文翻译：

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Guselkumab与secukinumab联合治疗中度至重度牛皮癣（ECLIPSE）：3期随机对照试验的结果

背景

靶向白介素（IL）-23和IL-17A的抗体可有效治疗中度至重度牛皮癣。ECLIPSE是IL-23p19抑制剂guselkumab与IL-17A抑制剂secukinumab的首个比较研究。这项研究的主要目的是显示在第48周时，古斯库单抗相对于苏金单抗的临床反应优越。

方法

在此第3阶段中，符合条件的患者在9个国家（澳大利亚，加拿大，捷克共和国，法国，德国，匈牙利，波兰，西班牙和美国）的142个门诊临床地点进行了多中心，双盲，随机，比较者对照的试验年龄在18岁或以上，患有中度至重度斑块型牛皮癣，可以进行光疗或全身疗法。符合条件的患者使用交互式网络响应系统随机分配置换块随机分组，以接受guselkumab（第0和4周分别100 mg，然后每8周一次）或secukinumab（第0、1、2、3和4周300 mg）然后每4周一次）。主要终点是在第48周时，自牛皮癣面积和严重性指数（PASI 90反应）的基线降低了90％或更多的意向治疗人群中的患者比例，和主要次要终点（在guselkumab组和secukinumab组中在第12周和第48周均达到PASI 75反应，在第12周时获得PASI 90反应，在第12周时获得PASI 75反应，在PASI 100时患者的比例在第48周时做出回应，在第48周时以固定顺序测试研究者的整体评估[IGA]评分为0 [已清除]，在第48周的IGA评分为0或1 [最低]）以控制I型错误速度。在第0周到第56周接受一剂或多剂研究药物的患者的安全性进行了评估。在第48周时，以固定顺序测试总体评估[IGA]评分为0 [已清除]，在第48周的IGA评分为0或1 [最小值]，以控制I型错误率。在第0周到第56周接受一剂或多剂研究药物的患者的安全性进行了评估。在第48周时，以固定顺序测试总体评估[IGA]评分为0 [已清除]，在第48周的IGA评分为0或1 [最小值]，以控制I型错误率。在第0周到第56周接受一剂或多剂研究药物的患者的安全性进行了评估。

发现

该研究于2017年4月27日至2018年9月20日之间进行。招募了1048例合格患者，其中534例接受古塞单抗治疗，514例接受苏金单抗治疗。guselkumab组（451 [84％]）在第48周时有PASI 90反应的患者比例高于苏金单抗组（360 [70％]； p <0·0001）。尽管在第一个主要的次要终点确定了非劣效性（10个百分点的差值）（在古斯库单抗组中有452 [85％]患者与secukinumab组中有412名[80％]患者在第12周和第48周均达到PASI 75反应），尚无优势（p = 0·0616）。因此，没有对随后的主要次要终点进行正式的统计测试。两种疗法之间发生不良事件，感染和严重不良事件的患者比例相似，并且总体而言，安全性研究结果与注册试验的观察结果一致。

解释

与secukinumab相比，Guselkumab在第48周显示出基于PASI 90的优越的长期疗效，可用于治疗中度至重度牛皮癣。这一发现可以帮助医疗保健提供者在选择用于治疗中度至重度牛皮癣的生物制剂时的决策过程。

资金

这项研究由Janssen Research＆Development资助。