Baseline ANA and Anti-Ro60/SSA Antibody as Potential Predictors for Immunogenicity and Poor EULAR Response in Adalimumab-Treated RA Patients

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yi-Ming Chen, Po-Ku Chen, Shih-Hsin Chang, Hsin-Hua Chen, Jun-Peng Chen, Kuo-Tung Tang, Joung-Liang Lan, Der-Yuan Chen
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Abstract

What Is Known and Objective. Given that autoantibodies are relatively abundant and easily measured, the detection of antibody biomarkers would be ideal for predicting therapeutic responses. Although anti-Ro60/SSA (anti-TROVE2) antibody has been identified as a useful predictor for the development of immunogenicity and therapeutic failure to adalimumab in RA patients, autoantibodies with similar predictive potentials are not yet sufficiently validated. Methods. We aimed to investigate the baseline autoantibodies, including rheumatoid factor (RF)-IgM, anti-citrullinated peptide antibodies (ACPA), antinuclear antibody (ANA), anti-Ro60/SSA antibody, and anti-La/SSB antibody, for their relationships with drug immunogenicity and therapeutic responses in RA patients assessed at week 48 of adalimumab therapy. We also compared adalimumab drug survival between participants with or without these autoantibodies. Results and Discussion. Our results showed that poor EULAR responders had significantly higher positive rates of baseline ANA, anti-Ro60/SSA antibody, and anti-La/SSB antibody than moderate or good responders. However, no significant differences in circulating levels of RF-IgM or ACPA were observed among groups with different responses. The multivariate logistic regression analysis revealed that ANA and anti-Ro60/SSA antibodies were significant predictors of developing immunogenicity to adalimumab (both p < 0.001). The presence of ANA, anti-Ro60/SSA, and anti-SSB antibodies could significantly predict poor EULAR response in adalimumab-treated RA patients (odds ratio, 4.98, 5.60, and 8.08, respectively, all p < 0.01). In Kaplan–Meier analysis, the adalimumab drug survival rate was significantly lower in RA patients with positivity for ANA, anti-Ro60/SSA, anti-SSB, and anti-drug antibodies than in the seronegative group. What Is New and Conclusion. Our results suggest that baseline ANA and anti-Ro60/SSA antibodies are potential predictive markers of drug immunogenicity and poor EULAR response in adalimumab-treated RA patients.

Abstract Image

基线ANA和抗Ro60/SSA抗体是阿达木单抗治疗的RA患者免疫原性和EULAR反应不佳的潜在预测因素
已知信息和目标。由于自身抗体相对丰富且易于测量,因此检测抗体生物标志物是预测治疗反应的理想方法。虽然抗Ro60/SSA(抗TROVE2)抗体已被确定为预测免疫原性发展和阿达木单抗在RA患者中治疗失败的有效指标,但具有类似预测潜力的自身抗体尚未得到充分验证。研究方法我们旨在研究基线自身抗体,包括类风湿因子(RF)-IgM、抗瓜氨酸肽抗体(ACPA)、抗核抗体(ANA)、抗Ro60/SSA抗体和抗La/SSB抗体,以了解它们与阿达木单抗治疗第48周时评估的RA患者药物免疫原性和治疗反应之间的关系。我们还比较了有无这些自身抗体的参与者的阿达木单抗药物存活率。结果与讨论。我们的结果显示,EULAR反应差者的基线ANA、抗Ro60/SSA抗体和抗La/SSB抗体阳性率明显高于中度或良好反应者。然而,不同反应组之间的RF-IgM或ACPA循环水平没有明显差异。多变量逻辑回归分析显示,ANA和抗Ro60/SSA抗体是阿达木单抗免疫原性发生的重要预测因素(均为p <0.001)。ANA、抗Ro60/SSA和抗SSB抗体的存在可显著预测阿达木单抗治疗的RA患者EULAR反应不佳的情况(几率分别为4.98、5.60和8.08,均为p <0.01)。在Kaplan-Meier分析中,ANA、抗Ro60/SSA、抗SSB和抗药物抗体阳性的RA患者的阿达木单抗药物存活率明显低于血清阴性组。新发现与结论。我们的研究结果表明,基线ANA和抗Ro60/SSA抗体是阿达木单抗治疗的RA患者药物免疫原性和EULAR反应不良的潜在预测指标。
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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