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类风湿关节炎患者中生物制剂和 Janus 激酶抑制剂的药物滞留:ANSWER 队列研究。

Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.

机构信息

Department of Musculoskeletal Regenerative Medicine, Osaka University Faculty of Medicine Graduate School of Medicine, Suita, Japan

Department of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of Medicine, Suita, Japan.

出版信息

RMD Open. 2023 Aug;9(3). doi: 10.1136/rmdopen-2023-003160.

Abstract

OBJECTIVES

This multicentre retrospective study in Japan aimed to assess the retention of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors (JAKi), and to clarify the factors affecting their retention in a real-world cohort of patients with rheumatoid arthritis.

METHODS

The study included 6666 treatment courses (bDMARD-naïve or JAKi-naïve cases, 55.4%; tumour necrosis factor inhibitors (TNFi) = 3577; anti-interleukin-6 receptor antibodies (aIL-6R) = 1497; cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig) = 1139; JAKi=453 cases). The reasons for discontinuation were divided into four categories (ineffectiveness, toxic adverse events, non-toxic reasons and remission); multivariate Cox proportional hazards modelling by potential confounders was used to analyse the HRs of treatment discontinuation.

RESULTS

TNFi (HR=1.93, 95% CI: 1.69 to 2.19), CTLA4-Ig (HR=1.42, 95% CI: 1.20 to 1.67) and JAKi (HR=1.29, 95% CI: 1.03 to 1.63) showed a higher discontinuation rate due to ineffectiveness than aIL-6R. TNFi (HR=1.28, 95% CI: 1.05 to 1.56) and aIL-6R (HR=1.27, 95% CI: 1.03 to 1.57) showed a higher discontinuation rate due to toxic adverse events than CTLA4-Ig. Concomitant use of oral glucocorticoids (GCs) at baseline was associated with higher discontinuation rate due to ineffectiveness in TNFi (HR=1.24, 95% CI: 1.09 to 1.41), as well as toxic adverse events in JAKi (HR=2.30, 95% CI: 1.23 to 4.28) and TNFi (HR=1.29, 95%CI: 1.07 to 1.55).

CONCLUSIONS

TNFi (HR=1.52, 95% CI: 1.37 to 1.68) and CTLA4-Ig (HR=1.14, 95% CI: 1.00 to 1.30) showed a higher overall drug discontinuation rate, excluding non-toxicity and remission, than aIL-6R.

摘要

目的

这项在日本开展的多中心回顾性研究旨在评估生物改善病情抗风湿药物和 Janus 激酶抑制剂(JAKi)的保留率,并阐明影响类风湿关节炎真实世界队列患者保留率的因素。

方法

本研究纳入了 6666 个治疗疗程(bDMARD 初治或 JAKi 初治病例,55.4%;肿瘤坏死因子抑制剂(TNFi)=3577 例;抗白细胞介素-6 受体抗体(aIL-6R)=1497 例;细胞毒性 T 淋巴细胞相关抗原-4-Ig(CTLA4-Ig)=1139 例;JAKi=453 例)。停药原因分为四类(无效、毒性不良反应、非毒性原因和缓解);采用潜在混杂因素的多变量 Cox 比例风险模型分析停药的 HR。

结果

与 aIL-6R 相比,TNFi(HR=1.93,95%CI:1.69 至 2.19)、CTLA4-Ig(HR=1.42,95%CI:1.20 至 1.67)和 JAKi(HR=1.29,95%CI:1.03 至 1.63)的无效停药率更高。与 CTLA4-Ig 相比,TNFi(HR=1.28,95%CI:1.05 至 1.56)和 aIL-6R(HR=1.27,95%CI:1.03 至 1.57)的毒性不良反应停药率更高。基线时同时使用口服糖皮质激素(GCs)与 TNFi 的无效停药率(HR=1.24,95%CI:1.09 至 1.41)以及 JAKi(HR=2.30,95%CI:1.23 至 4.28)和 TNFi(HR=1.29,95%CI:1.07 至 1.55)的毒性不良反应停药率更高。

结论

与 aIL-6R 相比,TNFi(HR=1.52,95%CI:1.37 至 1.68)和 CTLA4-Ig(HR=1.14,95%CI:1.00 至 1.30)的总停药率(排除非毒性和缓解因素)更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/680f/10441119/798fcdc9e0dc/rmdopen-2023-003160f01.jpg

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