Ixekizumab in children with active psoriatic and enthesitis-related juvenile idiopathic arthritis (COSPIRIT-JIA): a multicentre, open-label, 16-week, Bayesian trial including a randomised reference group to adalimumab.

Despite available treatments including non-steroidal anti-inflammatory drugs, glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs, a substantial proportion of people do not adequately respond to treatment or do not have long-lasting clinical remission.

尽管已有包括非甾体抗炎药、糖皮质激素、传统合成疾病修饰性抗风湿药物（DMARDs）和生物DMARDs在内的治疗方法，但仍有相当比例的人对治疗反应不足或没有持久的临床缓解。

The aim of this trial was to show the efficacy and safety of ixekizumab in children with active enthesitis-related arthritis and juvenile psoriatic arthritis.

本试验旨在展示ixekizumab在治疗活动性附着点相关性关节炎和幼年型银屑病关节炎儿童患者中的疗效和安全性。

Methods

COSPIRIT-JIA is an ongoing multicentre, open-label, phase 3 study of ixekizumab, with a randomised adalimumab reference group, in children with a diagnosis of enthesitis-related arthritis (aged 6 to <18 years) and juvenile psoriatic arthritis (aged 2 to <18 years).

COSPIRIT-JIA是一项正在进行的多中心、开放标签、3期研究，研究对象为被诊断为附着点相关性关节炎（6至<18岁）和幼年型银屑病关节炎（2至<18岁）的儿童，研究中包括了一个随机的阿达木单抗对照组。

Eligible participants had three or more active peripheral joints (presence of swelling or limited motion with pain or tenderness) and a bodyweight of at least 10 kg.

符合条件的参与者有三个或更多活动性外周关节（存在肿胀或活动受限伴有疼痛或压痛）以及至少10公斤的体重。

Participants received subcutaneous administration of either ixekizumab or adalimumab using a weight-based dosing regimen (ixekizumab 40-160 mg starting dose then 20-80 mg once every 4 weeks; and adalimumab 20-40 mg once every 2 weeks).

参与者接受了皮下注射依克珠单抗或阿达木单抗，使用基于体重的剂量方案（依克珠单抗起始剂量为40-160毫克，然后每4周一次20-80毫克；阿达木单抗每2周一次20-40毫克）。

The primary endpoint was the percentage of ixekizumab-treated participants meeting the JIA-American College of Rheumatology (ACR) 30 (defined as at least 30% improvement from baseline in three of any six core outcome variables, with no more than one of the other variables worsening by more than 30%) response criteria at week 16.

主要终点是接受ixekizumab治疗的参与者在第16周达到JIA-美国风湿病学会（ACR）30（定义为基线起至少30%改善在任意六个核心结果变量中的三个，且其他变量中不超过一个恶化超过30%）响应标准的百分比。

A Bayesian analysis was used to assess JIA-ACR30 response rate at week 16.

使用贝叶斯分析评估第16周的JIA-ACR30响应率。

Safety data were summarised using descriptive statistics for all participants who received at least one dose of either treatment.

使用描述性统计方法总结了所有至少接受一种治疗方案一次剂量的参与者的安全性数据。

People with lived experience of JIA were not involved in the design or conduct of this study.

本研究的设计或实施过程中没有涉及具有幼年特发性关节炎生活经历的人。

The trial was registered with ClinicalTrials.gov, NCT04527380.

该试验已在ClinicalTrials.gov注册，注册号为NCT04527380。

Results

The study enrolled 101 patients (ixekizumab n=81, adalimumab n=20) between April 13, 2021, and April 2, 2024, of whom the initial 40 participants naive to biological DMARD treatment were randomly assigned 1:1 to ixekizumab or adalimumab and the additional 61 participants were assigned to ixekizumab.

该研究在2021年4月13日至2024年4月2日期间共招募了101名患者（ixekizumab组81人，adalimumab组20人）。其中最初的40名未接受过生物制剂DMARD治疗的参与者被随机1:1分配到ixekizumab组或adalimumab组，另外的61名参与者被分配到ixekizumab组。

Of the 81 participants who received ixekizumab, 60 were biological DMARD naive (40 with enthesitis-related arthritis and 20 with juvenile psoriatic arthritis) and 21 were biological DMARD experienced (14 with enthesitis-related arthritis and seven with juvenile psoriatic arthritis).

在接受ixekizumab治疗的81名参与者中，有60人未曾使用过生物制剂DMARD（其中40人患有附着点炎相关性关节炎，20人患有青少年银屑病性关节炎），另外21人曾使用过生物制剂DMARD（其中14人患有附着点炎相关性关节炎，7人患有青少年银屑病性关节炎）。

The median age of the participants in the ixekizumab group was 14 years (12·0-15·0), of whom 36 (44%) of 81 were female, and 69 (85%) of 81 were White.

ixekizumab组参与者的中位年龄为14岁（12.0-15.0），在81名参与者中，有36人（占44%）为女性，有69人（占85%）为白人。

At week 16, 90% (54 of 60; 95% CI 82·4-97·6) of biological DMARD-naive participants and 86% (18 of 21; 70·7-100·0) of biological DMARD-experienced participants receiving ixekizumab had a JIA-ACR30 response.

在第16周时，90%（54/60；95% 置信区间82·4-97·6）的生物制剂疾病修饰性抗风湿药物（bDMARD）未经治疗的参与者和86%（18/21；70·7-100·0）的生物制剂疾病修饰性抗风湿药物经验过的参与者在接受ixekizumab治疗后，达到了JIA-ACR30的反应。

Treatment-emergent adverse events were mostly mild (46%) or moderate (36%) for the ixekizumab group, with no severe treatment-emergent adverse events reported.

ixekizumab组的治疗后不良事件大多为轻度（46%）或中度（36%），未报告任何严重的治疗后不良事件。

The safety profile was consistent with adult psoriatic arthritis or spondyloarthritis and paediatric psoriasis indications.

安全性特征与成人银屑病关节炎或脊柱关节炎以及儿童银屑病的适应症一致。

interpretation

Ixekizumab was well tolerated and effective for the treatment of children with enthesitis-related arthritis and juvenile psoriatic arthritis who are candidates for biological DMARD therapy.

依克珠单抗对生物制剂DMARD治疗的儿童附着点相关性关节炎和幼年型银屑病关节炎患者耐受性良好，疗效显著。

funding

Eli Lilly and Company.

礼来公司。