抗药抗体对接受阿达木单抗、依那西普或英夫利昔单抗治疗的类风湿关节炎患者药物浓度及临床结局的影响：一项跨国、真实世界临床实践、非干预性研究的结果
The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.
作者信息
Moots Robert J, Xavier Ricardo M, Mok Chi Chiu, Rahman Mahboob U, Tsai Wen-Chan, Al-Maini Mustafa H, Pavelka Karel, Mahgoub Ehab, Kotak Sameer, Korth-Bradley Joan, Pedersen Ron, Mele Linda, Shen Qi, Vlahos Bonnie
机构信息
Aintree University Hospital, University of Liverpool, Liverpool, United Kingdom.
Hospital de Clinicas, Porto Alegre, Brazil.
出版信息
PLoS One. 2017 Apr 27;12(4):e0175207. doi: 10.1371/journal.pone.0175207. eCollection 2017.
OBJECTIVE
To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes.
METHODS
This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6-24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected.
RESULTS
Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low.
CONCLUSION
ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA.
TRIAL REGISTRATION
This study was registered on www.ClinicalTrials.gov (NCT01981473).
目的
评估使用肿瘤坏死因子抑制剂依那西普（ETN）、阿达木单抗（ADL）或英夫利昔单抗（IFX）治疗的类风湿关节炎（RA）患者中抗药物抗体（ADA）的发生率，并确定其与血药谷浓度、疗效及患者报告结局之间的潜在关系。
方法
这项多国、非干预性横断面研究（NCT01981473）纳入了使用ETN、ADL或IFX持续治疗6至24个月的成年RA患者。在下一次预定给药前≤2天通过独立检测测定ADA和血药谷浓度。疗效指标包括28个关节疾病活动评分（DAS28）、低疾病活动度（LDA）、缓解情况及红细胞沉降率（ESR）。收集注射部位/输液反应、血清病及血栓栓塞事件的针对性病史。
结果
595例患者（ETN组：n = 200；ADL组：n = 199；IFX组：n = 196）的基线人口统计学特征在各组间相似。ETN、ADL和IFX的平均治疗时长分别为14.6、13.5和13.1个月。所有接受ETN治疗的患者ADA检测均为阴性，而接受ADL和IFX治疗的患者中，分别有31.2%和17.4%检测为阳性。在接受ADL或IFX治疗的患者中，ADA阳性患者的血药谷浓度显著更低。在接受ADL和IFX治疗的患者中，血药谷浓度与CRP和ESR均呈负相关。无ADA患者的DAS28-ESR LDA及缓解率更高。报告的针对性医疗事件发生率较低。
结论
在接受ADL和IFX治疗的患者中检测到ADA，而接受ETN治疗的患者中未检测到。无ADA患者的临床结局在数值上总体优于有ADA患者。
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