Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.

IF 20.3 1区 医学 Q1 RHEUMATOLOGY Annals of the Rheumatic Diseases Pub Date : 2024-07-30 DOI:10.1136/ard-2024-226024
Kristina Lend, Jon Lampa, Leonid Padyukov, Merete Lund Hetland, Marte Schrumpf Heiberg, Dan C Nordström, Michael T Nurmohamed, Anna Rudin, Mikkel Østergaard, Espen A Haavardsholm, Kim Hørslev-Petersen, Till Uhlig, Tuulikki Sokka-Isler, Bjorn Gudbjornsson, Gerdur Grondal, Giulia Frazzei, Jeroen Christiaans, Gertjan Wolbink, Theo Rispens, Jos W R Twisk, Ronald F van Vollenhoven
{"title":"Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.","authors":"Kristina Lend, Jon Lampa, Leonid Padyukov, Merete Lund Hetland, Marte Schrumpf Heiberg, Dan C Nordström, Michael T Nurmohamed, Anna Rudin, Mikkel Østergaard, Espen A Haavardsholm, Kim Hørslev-Petersen, Till Uhlig, Tuulikki Sokka-Isler, Bjorn Gudbjornsson, Gerdur Grondal, Giulia Frazzei, Jeroen Christiaans, Gertjan Wolbink, Theo Rispens, Jos W R Twisk, Ronald F van Vollenhoven","doi":"10.1136/ard-2024-226024","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT).</p><p><strong>Methods: </strong>Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking.</p><p><strong>Results: </strong>In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks.</p><p><strong>Conclusions: </strong>Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice.</p><p><strong>Trial registration number: </strong>EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of the Rheumatic Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/ard-2024-226024","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objectives: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT).

Methods: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking.

Results: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks.

Conclusions: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice.

Trial registration number: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
类风湿因子、抗瓜氨酸蛋白抗体和共同表位与早期类风湿关节炎患者对初始治疗的临床反应的关系:一项随机对照试验的数据。
研究目的研究类风湿因子(RF)、抗瓜氨酸蛋白抗体(ACPA)和共享表位(SE)等位基因相关遗传标记是否与阿帕塞普、certolizumab pegol或托珠单抗对积极常规治疗(ACT)的治疗反应有关:在NORD-STAR试验中,治疗无效的早期类风湿关节炎患者被随机分配到ACT、certolizumab pegol、阿巴特赛普或妥珠单抗治疗方案中,所有治疗方案均使用甲氨蝶呤。对ACPA、RF和SE进行了集中实验室分析。临床疾病活动指数缓解情况采用逻辑广义估计方程进行纵向分析。根据性别、国家、年龄、体重指数、基于C反应蛋白的28个关节的疾病活动度评分和吸烟情况进行调整后,在24周和48周用交互项评估了RF、ACPA和SE亚组的治疗效果差异:结果:共纳入了778名患者。24周时,在RF和/或ACPA阳性亚组中,阿帕他赛治疗的反应优于ACT,但这一效果与阴性亚组无显著差异。到48周时,无论RF/ACPA状态如何,阿帕他赛治疗都显示出更好的反应。48周时,RF、ACPA、SE等位基因、氨基酸第11位的缬氨酸或缬氨酸-精氨酸-丙氨酸单倍型亚组在任何生物治疗方面均未发现差异:根据这项随机对照试验,在24周时,阿巴他赛普治疗与RF和/或ACPA阳性亚组的ACT相比具有更好的应答相关性,但在48周时,这种相关性已不复存在;增加SE等位基因相关遗传标记并不能加强这种相关性。此外,ACPA、RF和SE等位基因相关基因型单独或组合与临床反应的相关性并不强,不足以在临床实践中应用:试验注册号:EudraCT 2011-004720-35;ClinicalTrials.gov NCT01491815。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Annals of the Rheumatic Diseases
Annals of the Rheumatic Diseases 医学-风湿病学
CiteScore
35.00
自引率
9.90%
发文量
3728
审稿时长
1.4 months
期刊介绍: Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
期刊最新文献
ITGA5+ synovial fibroblasts orchestrate proinflammatory niche formation by remodelling the local immune microenvironment in rheumatoid arthritis. Uncovering specific genetic-respiratory disease endotypes for rheumatoid arthritis risk. Vascular occlusion for optimising the functional improvement in patients with knee osteoarthritis: a randomised controlled trial. Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo-controlled, double-blind trial. Evidence that autoantibody production may be driven by acute Epstein-Barr virus infection in Sjögren's disease.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1