类风湿因子、抗瓜氨酸化蛋白抗体和共享表位与早期类风湿关节炎患者初始治疗临床反应的相关性：一项随机对照试验的数据。
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.
机构信息
Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
Division of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
出版信息
Ann Rheum Dis. 2024 Nov 14;83(12):1657-1665. doi: 10.1136/ard-2024-226024.
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.
目的
研究类风湿因子（RF）、抗瓜氨酸化蛋白抗体（ACPAs）和共享表位（SE）等位基因相关遗传标志物是否与阿巴西普、依那西普或托珠单抗相对于常规治疗（ACT）的治疗反应相关。
方法
在 NORD-STAR 试验中，将未经治疗的早期类风湿关节炎患者随机分为 ACT、依那西普、阿巴西普或托珠单抗组，所有患者均接受甲氨蝶呤治疗。对 ACPA、RF 和 SE 进行集中实验室分析。采用逻辑广义估计方程对临床疾病活动指数缓解情况进行纵向分析。在 24 周和 48 周时，通过交互项评估 RF、ACPA 和 SE 亚组间治疗效果的差异，并调整性别、国家、年龄、体重指数、基于 C 反应蛋白的 28 关节疾病活动评分和吸烟状况。
结果
共纳入 778 例患者。在 24 周时，与 ACT 相比，阿巴西普治疗在 RF 和/或 ACPA 阳性亚组中具有更好的反应，但与阴性亚组相比，这种差异无统计学意义。在 48 周时，无论 RF/ACPA 状态如何，阿巴西普治疗均显示出更好的反应。在 48 周时，对于任何生物治疗，RF、ACPA、SE 等位基因、第 11 位氨基酸缬氨酸、缬氨酸-精氨酸-丙氨酸单倍型亚组间无差异。
结论
基于这项随机对照试验，在 24 周时，与 ACT 相比，阿巴西普治疗在 RF 和/或 ACPA 阳性亚组中与更好的反应相关，但在 48 周时不再如此；添加 SE 等位基因相关遗传标志物并未增强这种关联。此外，ACPA、RF 和 SE 等位基因相关基因型单独或联合与临床重要反应的相关性均不够强，不足以在临床实践中实施。
试验注册号
EudraCT 2011-004720-35；ClinicalTrials.gov NCT01491815。
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