近日，加拿大蒙特利尔创新研究中心Robert Bissonnette团队研究了Icotrokinra治疗成人和青少年斑块型银屑病的疗效与安全性。相关论文发表在2025年11月6日出版的《新英格兰医学杂志》上。

Icotrokinra是一种选择性结合白介素-23受体的靶向口服肽，目前正在研究用于治疗斑块型银屑病。

研究组进行了一项3期、双盲、随机、安慰剂对照试验，涉及患有中度至重度斑块性银屑病的成人和青少年（≥12岁），其定义为以下所有：银屑病累及的体表总面积至少为10%，银屑病面积和严重程度指数（PASI）评分至少为12分（范围从0到72，分数越高表明银屑病的程度或严重程度越高），研究者总体评估（IGA）评分至少为3分（范围从0[皮肤清洁]到4[严重疾病]）。参与者以2:1的比例接受icotrokinra，剂量为200mg，每天一次，直到第24周，或安慰剂，直到第16周，然后过渡到icotrokinra。主要终点是第16周IGA 0/1缓解（IGA评分为0或1，较基线降低≥2分）和PASI 90缓解（PASI评分较基线降低≥90%）。

共有684名参与者接受了随机分组（456名至icotrokinra组，228名至安慰剂组）。在第16周，接受icotrokinra的参与者中有65%和接受安慰剂的参与者中有8%的人有IGA 0/1反应，分别有50%和4%的人有PASI 90缓解（P<0.001）。在第16周，icotrokinra组皮肤完全清除的可能性明显高于安慰剂组（IGA评分为0.33% vs. 1%； PASI评分为100缓解[PASI评分较基线降低100%]，27% vs. <1%; P<0.001）。到第16周，每组至少发生一次不良事件的参与者比例为49%；两组中最常见的不良事件是鼻咽炎和上呼吸道感染。经暴露调整后的不良事件发生率在第24周保持一致。

研究结果表明，口服靶向肽icotrokinra选择性阻断白介素-23受体，在中度至重度斑块型银屑病的成人和青少年患者中，16周时皮肤清除率明显高于安慰剂。长期数据将提供对icotrokinra的获益-风险概况更全面的了解。

附：英文原文

Title: Oral Icotrokinra for Plaque Psoriasis in Adults and Adolescents

Author: Robert Bissonnette, Jennifer Soung, Adelaide A. Hebert, Andrew E. Pink, Andreas Pinter, Angela Y. Moore, Yuling Shi, Wen-hui Wang, Darryl P. Toth, Megan Miller-Kassamali, Joseph Cafone, Jingzhi Jiang, Shu Li, Cynthia M.C. DeKlotz, Fabio Nunes, Mark G. Lebwohl

Issue&Volume: 2025-11-06

Abstract:

BACKGROUND

Icotrokinra, a targeted oral peptide that selectively binds the interleukin-23 receptor, is under investigation for the treatment of plaque psoriasis.

METHODS

We conducted a phase 3, double-blind, randomized, placebo-controlled trial involving adults and adolescents (≥12 years of age) with moderate-to-severe plaque psoriasis, as defined by all the following: a total body-surface area of psoriasis involvement of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12 (range, 0 to 72, with higher scores indicating a greater extent or severity of psoriasis), and an Investigator’s Global Assessment (IGA) score of at least 3 (range, 0 [clear skin] to 4 [severe disease]). Participants were assigned in a 2:1 ratio to receive icotrokinra at a dose of 200 mg once daily through week 24 or placebo through week 16 followed by transition to icotrokinra. The coprimary end points were an IGA 0/1 response (IGA score of 0 or 1 with ≥2-point reduction from baseline) and a PASI 90 response (≥90% reduction from baseline in the PASI score) at week 16.

RESULTS

A total of 684 participants underwent randomization (456 to the icotrokinra group and 228 to the placebo group). At week 16, a total of 65% of the participants receiving icotrokinra and 8% of those receiving placebo had an IGA 0/1 response, and 50% and 4%, respectively, had a PASI 90 response (P<0.001 for both comparisons). Complete clearance of skin at week 16 was significantly more likely with icotrokinra than with placebo (IGA score of 0, 33% vs. 1%; PASI 100 response [100% reduction from baseline in the PASI score], 27% vs. <1%; P<0.001 for both comparisons). The percentage of participants with at least one adverse event through week 16 was 49% in each group; the most common adverse events in each group were nasopharyngitis and upper respiratory tract infection. The exposure-adjusted incidence of adverse events was consistent through week 24.

CONCLUSIONS

Selective blockade of the interleukin-23 receptor with the targeted oral peptide icotrokinra resulted in a significantly higher incidence of skin clearance at week 16 than placebo among adults and adolescents with moderate-to-severe plaque psoriasis. Longer-term data will provide a more complete understanding of the benefit–risk profile of icotrokinra.

DOI: NJ202511063931808

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2504187