Abstract：
OBJECTIVE: 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.
BACKGROUND: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.
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.
BACKGROUND: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.
摘要：
目的：探讨类风湿因子（RF）抗瓜氨酸蛋白抗体（ACPAs）和共享表位（SE）等位基因相关的遗传标记与对abatacept的治疗反应相关，塞托珠单抗pegol或托珠单抗与主动常规治疗（ACT）的比较。
方法：在NORD-STAR试验中，初治早期类风湿性关节炎患者被随机分配到ACT，赛托珠单抗pegol，abatacept或tocilizumab，全部用甲氨蝶呤.ACPA的集中实验室分析，进行RF和SE。使用logistic广义估计方程对临床疾病活动指数缓解进行纵向分析。不同射频的治疗效果差异，ACPA和SE亚组在24周和48周时使用相互作用术语进行评估，适应性，国家,年龄,身体质量指数,基于C反应蛋白和吸烟的28个关节的疾病活动评分。
结果：总计，包括778名患者。24周时,在RF和/或ACPA阳性亚组中，abatacept治疗表现出比ACT更好的反应，但这一效应与阴性亚组无显著差异.到48周,无论RF/ACPA状态如何，abatacept治疗均显示出更好的反应。在RF中没有发现差异，ACPA,SE等位基因,氨基酸位置11的缬氨酸或缬氨酸-精氨酸-丙氨酸单倍型亚组，用于48周时的任何生物治疗。
结论：基于这项随机对照试验，在24周时，在RF和/或ACPA阳性亚组中，abatacept治疗的反应优于ACT，但这在48周时不再可见;添加SE等位基因相关的遗传标记并没有加强这种关联.此外，ACPA,RF和SE等位基因相关基因型没有，单独或组合，与重要的临床反应相关，足以保证在临床实践中实施。
背景：EudraCT2011-004720-35;ClinicalTrials.govNCT01491815。
方法：在NORD-STAR试验中，初治早期类风湿性关节炎患者被随机分配到ACT，赛托珠单抗pegol，abatacept或tocilizumab，全部用甲氨蝶呤.ACPA的集中实验室分析，进行RF和SE。使用logistic广义估计方程对临床疾病活动指数缓解进行纵向分析。不同射频的治疗效果差异，ACPA和SE亚组在24周和48周时使用相互作用术语进行评估，适应性，国家,年龄,身体质量指数,基于C反应蛋白和吸烟的28个关节的疾病活动评分。
结果：总计，包括778名患者。24周时,在RF和/或ACPA阳性亚组中，abatacept治疗表现出比ACT更好的反应，但这一效应与阴性亚组无显著差异.到48周,无论RF/ACPA状态如何，abatacept治疗均显示出更好的反应。在RF中没有发现差异，ACPA,SE等位基因,氨基酸位置11的缬氨酸或缬氨酸-精氨酸-丙氨酸单倍型亚组，用于48周时的任何生物治疗。
结论：基于这项随机对照试验，在24周时，在RF和/或ACPA阳性亚组中，abatacept治疗的反应优于ACT，但这在48周时不再可见;添加SE等位基因相关的遗传标记并没有加强这种关联.此外，ACPA,RF和SE等位基因相关基因型没有，单独或组合，与重要的临床反应相关，足以保证在临床实践中实施。
背景：EudraCT2011-004720-35;ClinicalTrials.govNCT01491815。
