The impact of antinuclear antibodies seroconversion induced by anti-tumor necrosis factor α agents on the clinical outcomes in rheumatic patients.

IF 1.4 4区 医学 Q3 RHEUMATOLOGY ARP Rheumatology Pub Date : 2023-04-12
Ana Martins, Daniela Oliveira, Frederico Rajão Martins, Maria Seabra Rato, Filipe Oliveira Pinheiro, Diogo Fonseca, Salomé Garcia, Bruno Miguel Fernandes, Sofia Pimenta, Carlos Vaz, Lúcia Costa, Miguel Bernardes
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Abstract

Introduction: Anti-tumor necrosis factor α (anti-TNFα) agents can potentially induce the anti-nuclear antibodies (ANA) development over time. Evidence of the real impact of these autoantibodies on clinical response to treatment in rheumatic patients is still scarce.

Objectives: To explore the impact of ANA seroconversion induced by anti-TNFα therapy on clinical outcomes in biologic-naïve patients with Rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and psoriatic arthritis (PsA).

Methods: An observational retrospective cohort study enrolling biologic-naïve patients with RA, axSpA and PsA who started their first anti-TNFα agent was conducted for 24 months(M). Sociodemographic data, laboratory findings, disease activity and physical function scores were collected at baseline, 12M and 24M. To examine the differences between the groups with and without ANA seroconversion, independent samples t-tests, Mann-Whitney U-tests and chi-square tests were performed. Linear and logistic regression models were used to assess the effects of ANA seroconversion on the clinical response to treatment.

Results: A total of 432 patients with RA (N=185), axSpA (N=171) and PsA (N=66) were included. ANA seroconversion rate at 24M was 34.6%, 64.3% and 63.6% for RA, axSpA and PsA, respectively. Regarding sociodemographic and clinical data in RA and PsA patients, no statistically significant differences between groups with and without ANA seroconversion were found. In axSpA patients, ANA seroconversion was more frequent in patients with higher body mass index (p=0.017) and significantly less frequent in patients treated with etanercept (p=0.01). Regarding disease activity, DAS28 for RA patients and ASDAS-CRP for axSpA patients were significantly higher in ANA seroconversion group at 12M (p=0.017 and p=0.009, respectively). For PsA patients, CDAI was significantly higher in ANA seroconversion group at 24M (p=0.043). Overall switching rate of biologic disease-modifying antirheumatic drugs (bDMARD) was significantly higher in the ANA seroconversion group over time (p=0.025). For RA patients, ANA seroconversion predicted DAS28 (β=-0.21, 95%CI[-1.86;-0.18], p=0.017) at 12M.

Conclusions: ANA seroconversion induced by anti-TNFα agents could interfere in clinical response of patients with rheumatic diseases. The presence of these autoantibodies can be considered as a potential predictor of poor treatment response and higher need for bDMARD switching over time.

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抗肿瘤坏死因子α诱导的抗核抗体血清转化对风湿病患者临床预后的影响。
导论:抗肿瘤坏死因子α (anti- tnf - α)药物可随时间诱导抗核抗体(ANA)的产生。这些自身抗体对风湿病患者治疗的临床反应的真正影响的证据仍然很少。目的:探讨抗tnf α治疗诱导ANA血清转化对biologic-naïve类风湿性关节炎(RA)、轴型颈椎炎(axSpA)和银屑病关节炎(PsA)患者临床结局的影响。方法:一项观察性回顾性队列研究纳入biologic-naïve RA, axSpA和PsA患者,他们开始使用第一个抗tnf α药物,为期24个月(M)。在基线、12M和24M收集社会人口学数据、实验室结果、疾病活动和身体功能评分。采用独立样本t检验、Mann-Whitney u检验和卡方检验来检验有无ANA血清转化组之间的差异。采用线性和逻辑回归模型评估ANA血清转化对临床治疗反应的影响。结果:共纳入432例RA (N=185), axSpA (N=171)和PsA (N=66)。24M时,RA、axSpA和PsA的ANA血清转化率分别为34.6%、64.3%和63.6%。关于RA和PsA患者的社会人口学和临床数据,ANA血清转换组和非ANA血清转换组之间无统计学差异。在axSpA患者中,ANA血清转换在体重指数较高的患者中更频繁(p=0.017),而在依那西普治疗的患者中更少(p=0.01)。在疾病活动性方面,ANA血清转换组在12M时RA患者的DAS28和axSpA患者的ASDAS-CRP显著升高(p=0.017和p=0.009)。对于PsA患者,ANA血清转换组在24M时CDAI显著升高(p=0.043)。随着时间的推移,ANA血清转换组生物疾病缓解抗风湿药物(bDMARD)的总转换率显著更高(p=0.025)。对于RA患者,ANA血清转换预测12M时DAS28 (β=-0.21, 95%CI[-1.86;-0.18], p=0.017)。结论:抗tnf α药物诱导的ANA血清转化可干扰风湿病患者的临床反应。这些自身抗体的存在可以被认为是治疗反应差和bDMARD转换需求增加的潜在预测因子。
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