本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2308713

摘要内容如下：

背景

单克隆抗体的使用改变了包括银屑病在内的几种免疫介导的炎症性疾病的治疗。然而，这些大的蛋白质必须通过注射给药。JNJ-77242113是一种新型的口服白细胞介素-23受体拮抗肽，可选择性阻断白细胞介素-23信号传导和下游细胞因子的产生。

方法

在该2期剂量探索试验中，我们将中度至重度斑块型银屑病患者随机分配接受JNJ-77242113，剂量为25 mg每日一次、25 mg每日两次、50 mg每日一次、100 mg每日一次或100 mg每日两次或安慰剂，为期16周。主要终点是银屑病面积和严重性指数（PASI）评分从基线至少减少75%（PASI 75反应；在第16周，PASI评分范围为0至72，评分越高表明银屑病的程度或严重性越大。

结果

共有255名患者接受了随机分组。基线时的平均PASI评分为19.1。银屑病的平均持续时间为18.2年，所有试验组中78%的患者以前接受过系统治疗。在第16周，JNJ-77242113组中出现PASI 75反应的患者百分比（25 mg每日一次组、25 mg每日两次组、50 mg每日一次组、100 mg每日一次组和100 mg每日两次组分别为37%、51%、58%、65%和79%）高于安慰剂组（9%），这一发现显示了显著的剂量反应关系（P<0.001）。最常见的不良事件包括冠状病毒病2019（12%的安慰剂组患者和11%的JNJ-77242113剂量组患者）和鼻咽炎（分别为5%和7%）。在联合JNJ-77242113剂量组（52%）和安慰剂组（51%）中，至少发生一次不良事件的患者百分比相似。没有证据表明JNJ-77242113剂量组的不良事件增加与剂量相关。

结论

每天一次或两次口服给药16周后，白细胞介素-23受体拮抗肽JNJ-77242113治疗中重度斑块型银屑病患者的疗效优于安慰剂。（由杨森研发公司资助；Frontier 1 ClinicalTrials.gov编号，NCT05223868。）

英文原文如下：

Abstracts

BACKGROUND  The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production.

METHODS  In this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16.

RESULTS  A total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose-response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups.

CONCLUSIONS  After 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23-receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.).

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