Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial

医学 托珠单抗 安慰剂 内科学 双盲 临床试验 梅德林 病理 类风湿性关节炎 法学 政治学 替代医学
作者
Dinesh Khanna,Celia J. F. Lin,Daniel E. Furst,Jonathan Goldin,Grace Kim,Masataka Kuwana,Yannick Allanore,Marco Matucci‐Cerinic,Oliver Distler,Yoshihito Shima,Jacob M. van Laar,Helen Spotswood,Bridget K. Wagner,Jeffrey Siegel,Angelika Jahreis,Christopher P. Denton,Eleonora Lucero,Bernardo A. Pons‐Estel,Mariano Rivero,Guillermo Tate
出处
期刊:The Lancet Respiratory Medicine [Elsevier BV]
卷期号:8 (10): 963-974 被引量:521
标识
DOI:10.1016/s2213-2600(20)30318-0
摘要

Summary

Background

A phase 2 trial of tocilizumab showed preliminary evidence of efficacy in systemic sclerosis. We assessed skin fibrosis and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in a phase 3 trial to investigate the safety and efficacy of tocilizumab, an anti-interleukin-6 receptor antibody, in the treatment of systemic sclerosis.

Methods

In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial, participants were recruited from 75 sites in 20 countries across Europe, North America, Latin America, and Japan. Adults with diffuse cutaneous systemic sclerosis for 60 months or less and a modified Rodnan skin score (mRSS) of 10–35 at screening were randomly assigned (1:1) with a voice-web-response system to receive subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks, stratified by IL-6 levels; participants and investigators were masked to treatment group. The primary endpoint was the difference in change from baseline to week 48 in mRSS. Percentage of predicted forced vital capacity (FVC% predicted) at week 48, time to treatment failure, and patient-reported and physician-reported outcomes were secondary endpoints. This trial is registered with ClinicalTrials.gov (number NCT02453256) and is closed to accrual.

Findings

Between Nov 20, 2015, and Feb 14, 2017, 210 individuals were randomly assigned to receive tocilizumab (n=104) or placebo (n=106). In the intention-to-treat population, least squares mean [LSM] change from baseline to week 48 in mRSS was −6·14 for tocilizumab and −4·41 for placebo (adjusted difference −1·73 [95% CI −3·78 to 0·32]; p=0·10). The shift in distribution of change from baseline in FVC% predicted at week 48 favoured tocilizumab (van Elteren nominal p=0·002 vs placebo), with a difference in LSM of 4·2 (95% CI 2·0–6·4; nominal p=0·0002), as did time to treatment failure (hazard ratio 0·63 [95% CI 0·37–1·06]; nominal p=0·08). Change in LSM from baseline to week 48 in Health Assessment Questionnaire-Disability Index and in patient-global and physician-global visual analogue scale assessments did not differ between tocilizumab and placebo. In the safety set, infections were the most common adverse events (54 [52%] of 104 participants in the tocilizumab group, 53 [50%] of 106 in the placebo group). Serious adverse events were reported in 13 participants treated with tocilizumab and 18 with placebo, primarily infections (three events, eight events) and cardiac events (two events, seven events).

Interpretation

The primary skin fibrosis endpoint was not met. Findings for the secondary endpoint of FVC% predicted indicate that tocilizumab might preserve lung function in people with early SSc-ILD and elevated acute-phase reactants. Safety was consistent with the known profile of tocilizumab.

Funding

F Hoffmann-La Roche Ltd.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
哈哈哈哈完成签到,获得积分10
刚刚
1秒前
生椰拿铁不加生椰完成签到 ,获得积分10
2秒前
认真的灵竹完成签到 ,获得积分10
3秒前
Zxx关注了科研通微信公众号
4秒前
4秒前
franca2005完成签到 ,获得积分10
4秒前
本末倒纸完成签到 ,获得积分10
6秒前
wbscz应助星辰采纳,获得10
6秒前
toxikon发布了新的文献求助10
7秒前
8秒前
10秒前
大模型应助剁辣椒蒸鱼头采纳,获得20
10秒前
小北完成签到 ,获得积分10
10秒前
11秒前
高挑的冰露完成签到 ,获得积分10
14秒前
ruochenzu发布了新的文献求助10
14秒前
老李完成签到,获得积分10
14秒前
15秒前
16秒前
tough_cookie完成签到 ,获得积分10
17秒前
彩钢房完成签到,获得积分10
18秒前
MeSs完成签到 ,获得积分10
19秒前
toxikon完成签到,获得积分10
20秒前
一点通完成签到,获得积分10
20秒前
Lei完成签到,获得积分10
21秒前
21秒前
21秒前
常若冰完成签到,获得积分10
21秒前
纯真的元风完成签到,获得积分10
22秒前
哇哈哈哈完成签到,获得积分10
22秒前
清秋1001完成签到 ,获得积分10
23秒前
qq完成签到,获得积分10
24秒前
荒野风发布了新的文献求助10
25秒前
Zxx发布了新的文献求助10
26秒前
27秒前
27秒前
确幸完成签到 ,获得积分10
27秒前
苒苒完成签到,获得积分10
27秒前
28秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038619
求助须知:如何正确求助?哪些是违规求助? 3576294
关于积分的说明 11375058
捐赠科研通 3306084
什么是DOI,文献DOI怎么找? 1819374
邀请新用户注册赠送积分活动 892698
科研通“疑难数据库(出版商)”最低求助积分说明 815066