Oral Icotrokinra for Plaque Psoriasis in Adults and Adolescents.

Methods

We conducted a phase 3, double-blind, randomized, placebo-controlledtrial 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]).

我们进行了一项3期、双盲、随机、安慰剂对照试验，涉及成人和青少年（≥12岁）的中度至重度斑块型银屑病患者，其定义如下：银屑病受累的总体表面积至少为10%，银屑病面积和严重程度指数（PASI）至少为12（范围，0至72，分数越高表示银屑病的范围或严重程度越大），以及研究者总体评估（IGA）得分至少为3（范围，0[皮肤清晰]至4[严重疾病]）。

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.

参与者按照2:1的比例被分配，接受icotrokinra 200 mg每日一次，持续至第24周，或接受安慰剂至第16周后转为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.

共同主要终点是第16周时的IGA 0/1反应（IGA评分为0或1，且从基线起至少降低2分）和PASI 90反应（从基线起PASI评分至少降低90%）。

Results

A total of 684 participants underwent randomization (456 to the icotrokinra group and 228 to the placebo group).

共有684名参与者进行了随机分组（456人分到icotrokinra组，228人分到安慰剂组）。

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).

在第16周时，接受icotrokinra治疗的参与者中有65%达到了IGA 0/1级反应，而接受安慰剂治疗的参与者中这一比例为8%；同时，达到PASI 90反应的分别有50%和4%（两者比较P<0.001）。

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).

在第16周时，使用icotrokinra的患者比使用安慰剂的患者更有可能实现皮肤完全清除（IGA评分为0，33%对1%；PASI 100反应[基线 PASI 评分100%降低]，27%对<1%；两者比较P<0.001）。

The percentage of participants with at least one adverse eventthrough week 16 was 49% in each group; the most common adverse events in each group were nasopharyngitis and upper respiratory tract infection.

截至第16周，每组有49%的参与者至少出现一次不良事件；每组中最常见的不良事件是鼻咽炎和上呼吸道感染。

The exposure-adjusted incidenceof adverse events was consistent through week 24.

不良事件的调整暴露发生率在第24周时保持一致。

Conclusions

Selective blockade of the interleukin-23 receptor with the targeted oral peptide icotrokinra resulted in a significantly higher incidenceof skin clearance at week 16 than placebo among adults and adolescents with moderate-to-severe plaque psoriasis.

选择性阻断白细胞介素-23受体的靶向口服肽类药物依克珠单抗，在第16周时，与安慰剂相比，导致中重度斑块型银屑病成人和青少年的皮肤清除率显著更高。

Longer-term data will provide a more complete understanding of the benefit-risk profile of icotrokinra.

更长期的数据将提供对icotrokinra效益-风险概况更全面的理解。

(Funded by Johnson & Johnson; ICONIC-LEAD ClinicalTrials.gov number, NCT06095115.)See also in NEJM Evidence: Targeted Oral Peptide Icotrokinra for Psoriasis Involving High‑Impact Sites.

(由强生公司资助；ICONIC-LEAD 临床试验注册号，NCT06095115。)亦见于NEJM Evidence: 针对影响重大部位的银屑病的靶向口服肽icotrokinra。