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类风湿关节炎中生物制剂和靶向合成 DMARDs 的药物生存预测因素:来自 TRA 临床电子注册的分析。

Predictors of drug survival for biologic and targeted synthetic DMARDs in rheumatoid arthritis: Analysis from the TRA Clinical Electronic Registry.

机构信息

Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.

Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

PLoS One. 2021 Apr 30;16(4):e0250877. doi: 10.1371/journal.pone.0250877. eCollection 2021.

Abstract

In this study we aimed to identify the predictors of drug survival for biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) among patients with rheumatoid arthritis (RA) in a real-world setting. Data from RA patients receiving bDMARDs and tsDMARDs between 2007 and 2019 were extracted from the Taiwan Rheumatology Association Clinical Electronic Registry (TRACER). Patients were categorized into tumor necrosis factor-alpha (TNF-α) inhibitors, non-TNF-α inhibitors, and tofacitinib groups. The primary outcome was 3-year drug retention and the causes of bDMARDs and tsDMARDs discontinuation were recorded. Baseline demographic data before the initiation of bDMARDs and tsDMARDs treatment were analyzed to identify the predictors of 3-year drug survival. A total of 1,270 RA patients were recruited (TNF-α inhibitors: 584; non-TNF-α inhibitors: 535; tofacitinib: 151). The independent protective factors for 3-year drug survival were positive rheumatoid factor (RF) (HR: 0.48, 95% CI: 0.27-0.85, p = 0.013) and biologics-naïve RA (HR: 0.61, 95% CI: 0.39-0.94, p = 0.024). In contrast, positive anti-citrullinated protein antibody (ACPA) (HR: 2.24, 95% CI: 1.32-3.79, p = 0.003) and pre-existing latent tuberculosis (HR: 2.90, 95% CI: 2.06-4.09, p<0.001) were associated with drug discontinuation. RA patients treated with TNF-α inhibitors exhibited better drug retention, especially in the biologics-naïve subgroup (p = 0.037). TNF-α inhibitors were associated with lower cumulative incidence of discontinuation due to inefficacy and adverse events (both p<0.001). Baseline RF and ACPA positivity in abatacept-treated patients were associated with a better 3-year drug survival. However, negative ACPA levels predicted superior drug survival of TNF-α inhibitors and tofacitinib. In conclusion, bio-naïve status predicted better drug survival in TNF-α inhibitors-treated RA patients. RF and ACPA positivity predicted better abatacept drug survival. In contrast, ACPA negativity was associated with superior TNF-α inhibitors and tofacitinib survival.

摘要

在这项研究中,我们旨在确定在真实环境中类风湿关节炎(RA)患者使用生物制剂和靶向合成疾病修正抗风湿药物(bDMARDs 和 tsDMARDs)的药物生存预测因素。从台湾风湿病学会临床电子注册处(TRACER)中提取了 2007 年至 2019 年间接受 bDMARDs 和 tsDMARDs 治疗的 RA 患者的数据。患者分为肿瘤坏死因子-α(TNF-α)抑制剂、非 TNF-α 抑制剂和托法替尼组。主要结局是 3 年药物保留率,并记录 bDMARDs 和 tsDMARDs 停药的原因。分析 bDMARDs 和 tsDMARDs 治疗前的基线人口统计学数据,以确定 3 年药物生存的预测因素。共招募了 1270 名 RA 患者(TNF-α 抑制剂:584 名;非 TNF-α 抑制剂:535 名;托法替尼:151 名)。3 年药物生存的独立保护因素是阳性类风湿因子(RF)(HR:0.48,95%CI:0.27-0.85,p=0.013)和生物制剂初治 RA(HR:0.61,95%CI:0.39-0.94,p=0.024)。相比之下,阳性抗瓜氨酸蛋白抗体(ACPA)(HR:2.24,95%CI:1.32-3.79,p=0.003)和潜伏性结核既往史(HR:2.90,95%CI:2.06-4.09,p<0.001)与停药相关。接受 TNF-α 抑制剂治疗的 RA 患者药物保留率更好,尤其是在生物制剂初治亚组(p=0.037)。TNF-α 抑制剂与因疗效不佳和不良反应而停药的累积发生率较低(均 p<0.001)有关。阿巴西普治疗患者的基线 RF 和 ACPA 阳性与 3 年药物生存更好相关。然而,阴性 ACPA 水平预测 TNF-α 抑制剂和托法替尼的药物生存更好。总之,生物制剂初治状态预测 TNF-α 抑制剂治疗的 RA 患者药物生存更好。RF 和 ACPA 阳性预测阿巴西普药物生存更好。相反,ACPA 阴性与 TNF-α 抑制剂和托法替尼的生存更好相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abed/8087098/ae0ed866a73f/pone.0250877.g001.jpg

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