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影响类风湿关节炎患者生物学生存的因素:荷兰真实世界学术队列研究结果。

Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands.

机构信息

Department of Rheumatology, Erasmus MC, Room Na-523, Postbus 2040, 3000 CA, Rotterdam, the Netherlands.

Department of Rheumatology, Maasstad Hospital, Rotterdam, the Netherlands.

出版信息

Clin Rheumatol. 2021 Jun;40(6):2177-2183. doi: 10.1007/s10067-020-05567-6. Epub 2021 Jan 7.

Abstract

We aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0-7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3-2.2) and 0.8 years (95% CI, 0.5-1.0) (p = 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), remission (16%), pregnancy (30%), or patient preference (10%). Multivariable Cox regression analyses for discontinuation due to inefficacy or adverse events showed that concomitant use of csDMARDs (HR = 1.32, p < 0.001) positively while RF positivity negatively (HR = 0.82, p = 0.03) influenced biological survival. ACPA positivity was associated with the inability to discontinue biologicals after achieving remission (HR = 1.43, p = 0.023). Second-line TNF inhibitor survival was similar between patients with a primary and secondary non-response on the first-line TNF inhibitor (HR = 1.28, p = 0.34). Biological survival diminishes with the number of biologicals used. Biological survival is prolonged if patients use csDMARDs. RF was negatively associated with biological survival. ACPA was negatively associated with the inability to discontinue biologicals after achieving remission. Therefore, tailoring treatment based upon autoantibody status might be the first step towards personalized medicine in RA. Key Points • Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored. • We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached. • The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.

摘要

我们旨在探索基于停药原因的生物生存的真实世界分层,并确定其对类风湿关节炎 (RA) 患者的影响。使用了荷兰一所大学医院的当地药房数据库和患者记录中的数据。纳入了 2000 年至 2020 年间开始使用生物制剂的 RA 患者。收集了年龄、抗瓜氨酸蛋白抗体 (ACPA) 和类风湿因子 (RF) 状态、是否存在侵蚀、性别、体重指数、首次生物制剂的时间、生物制剂生存时间、csDMARD 的使用情况以及停药原因等数据。在纳入的 318 名患者中,有 12%的患者在确诊后 6 个月内开始使用他们的第一种生物制剂。首次生物制剂的中位时间为 3.6 年(95%CI,1.0-7.2)。一线和二线生物制剂的中位生存时间分别为 1.7 年(95%CI,1.3-2.2)和 0.8 年(95%CI,0.5-1.0)(p=0.0001)。一线生物制剂停药的原因分别为无效(47%)、不良反应(17%)、缓解(16%)、妊娠(30%)或患者偏好(10%)。多变量 Cox 回归分析显示,因无效或不良反应而停药与同时使用 csDMARDs(HR=1.32,p<0.001)呈正相关,而 RF 阳性(HR=0.82,p=0.03)呈负相关,影响生物制剂的生存。ACPA 阳性与实现缓解后无法停止生物制剂治疗有关(HR=1.43,p=0.023)。在一线 TNF 抑制剂治疗原发性和继发性无应答的患者中,二线 TNF 抑制剂的生存相似(HR=1.28,p=0.34)。使用的生物制剂数量越多,生物制剂的生存时间越短。如果患者使用 csDMARDs,则生物制剂的生存时间延长。RF 与生物制剂的生存呈负相关。ACPA 与达到缓解后无法停止生物制剂治疗有关。因此,基于自身抗体状态调整治疗可能是 RA 迈向个体化医学的第一步。要点 • 延长生物制剂的生存时间是治疗有效性的替代指标;然而,由于缓解,越来越多的患者将减少治疗,并且尚未探索基于停药的不同原因的生物制剂生存时间的影响因素。 • 我们发现,联合使用生物 DMARD 和传统合成 DMARD 可延长生物 DMARD 的生存时间。RF 与生物制剂的生存呈负相关。当达到缓解时,ACPA 与无法停止生物制剂治疗有关。 • 基于自身抗体状态调整治疗可能是迈向个体化医学的第一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4315/8121743/e736774d39a7/10067_2020_5567_Fig1_HTML.jpg

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