生物性和靶向合成抗风湿药物对类风湿关节炎患者新发慢性肾脏病的比较效果。

Comparative effects of biological and targeted synthetic DMARDs on incident chronic kidney disease in patients with rheumatoid arthritis.

作者信息

Nishimura Nozomi, Onishi Akira, Yamamoto Wataru, Nagai Koji, Shiba Hideyuki, Okita Yasutaka, Son Yonsu, Amuro Hideki, Okano Takaichi, Ueda Yo, Hara Ryota, Katayama Masaki, Yamada Shinsuke, Hashimoto Motomu, Maeda Yuichi, Onizawa Hideo, Fujii Takayuki, Murata Koichi, Murakami Kosaku, Tanaka Masao, Matsuda Shuichi, Morinobu Akio

机构信息

Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Department of Advanced Medicine for Rheumatic diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

出版信息

Rheumatology (Oxford). 2025 May 1;64(5):2395-2402. doi: 10.1093/rheumatology/keae603.

DOI:10.1093/rheumatology/keae603

PMID:39475445

Abstract

OBJECTIVES

The impact of individual biological/targeted synthetic DMARD (b/tsDMARD) on kidney function in patients with RA remains unclear. This study aimed to determine the comparative effects of b/tsDMARDs on chronic kidney disease (CKD) incidence in patients with RA.

METHODS

This multicentre cohort study included patients with RA who had baseline estimated glomerular filtration rate (eGFR) of ≥60 ml/min/1.73 m2 and started a TNF inhibitor (TNFi), cytotoxic T-lymphocyte-associated antigen-4-Ig (CTLA4-Ig), interleukin-6 receptor inhibitor, or Janus kinase inhibitor (JAKi) in Japan. Multiple propensity score-based inverse probability weighting (IPW) was used to adjust confounders. The incidence of CKD was compared among b/tsDMARDs using IPW mixed-effect Cox proportional hazards models and linear mixed-effect models with IPW-examined trajectories of eGFR.

RESULTS

Among 2187 patients with 3068 treatment courses and up to 11 years of follow-up, CKD occurred in 275 cases. Compared with the CTLA4-Ig group, the TNFi group had a significantly lower CKD incidence [hazard ratio (HR) 0.67, 95% CI 0.46-0.97, P = 0.04], whereas the JAKi group had a significantly higher incidence (HR 2.16, 95% CI 1.23-3.79, P = 0.01). The trajectory of eGFR was significantly greater in the JAKi group than in the CTLA4-Ig group (CTLA4-Ig: -1.28 ml/min/1.73 m2/year, JAKi: -2.29 ml/min/1.73 m2/year, P < 0.001).

CONCLUSIONS

TNFi use was associated with reduced CKD incidence, whereas JAKi showed a less protective association for kidney function in patients with RA.

摘要

目的

单个生物制剂/靶向合成改善病情抗风湿药（b/tsDMARD）对类风湿关节炎（RA）患者肾功能的影响尚不清楚。本研究旨在确定b/tsDMARDs对RA患者慢性肾脏病（CKD）发病率的比较效果。

方法

这项多中心队列研究纳入了在日本开始使用肿瘤坏死因子抑制剂（TNFi）、细胞毒性T淋巴细胞相关抗原4-免疫球蛋白（CTLA4-Ig）、白细胞介素-6受体抑制剂或Janus激酶抑制剂（JAKi），且基线估计肾小球滤过率（eGFR）≥60 ml/min/1.73 m²的RA患者。采用基于多重倾向评分的逆概率加权（IPW）法调整混杂因素。使用IPW混合效应Cox比例风险模型和具有IPW检验的eGFR轨迹的线性混合效应模型，比较b/tsDMARDs之间CKD的发病率。

结果

在2187例患者的3068个治疗疗程及长达11年的随访中，275例发生了CKD。与CTLA4-Ig组相比，TNFi组的CKD发病率显著更低[风险比（HR）0.67，95%置信区间（CI）0.46-0.97，P = 0.04]，而JAKi组的发病率显著更高（HR 2.16，95% CI 1.23-3.79，P = 0.01）。JAKi组的eGFR轨迹显著大于CTLA4-Ig组（CTLA4-Ig：-1.28 ml/min/1.73 m²/年，JAKi：-2.29 ml/min/1.73 m²/年，P < 0.001）。