Lee Jung Sun, Oh Ji Seon, Kim Yong-Gil, Lee Chang-Keun, Yoo Bin, Hong Seokchan
Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
Division of Rheumatology, Department of Internal Medicine, Seoul Veterans Hospital, Seoul, South Korea.
Rheumatol Int. 2020 May;40(5):765-770. doi: 10.1007/s00296-020-04547-y. Epub 2020 Mar 13.
There are limited studies regarding the safety of methotrexate (MTX) in patients with reduced renal function. This study aimed to investigate methotrexate (MTX)-related toxicity in patients with rheumatoid arthritis (RA) and renal dysfunction. This retrospective cohort study included patients with RA and renal dysfunction. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m. We classified the patients into two groups according to the onset of renal dysfunction: newly and previously developed group. MTX-associated toxicity included renal toxicity, hepatotoxicity, serious infection, pancytopenia, leukopenia, thrombocytopenia and mucositis. Cox analysis was performed to determine the factors associated with toxicity. The study included 120 patients with RA and renal dysfunction receiving MTX (66: newly developed; 54: previously developed). The median eGFR was 52.1 mL/min/1.73 m [IQR 47.1-57.3]. Thirty-five patients (29.2%) experienced toxicity, and the median time to toxicity events was 23 months (IQR 10-57). Toxicity was distributed as follows: leukopenia (10%, 12/120), renal toxicity (5.8%, 7/120), hepatotoxicity (7.5%, 9/120), serious infection (8.3%, 10/120), pancytopenia (5.0%, 6/120), thrombocytopenia (5.8%, 7/120), and mucositis (5.8%, 7/120). The toxicity rate did not differ significantly between newly and previously developed group [23/66 (34.8%) vs. 12/54 (22.2%), P = 0.130]. Multivariate analysis revealed that hydroxychloroquine use (HR 0.425, 95% CI 0.212-0.853, P = 0.016), baseline eGFR (HR 0.938, 95% CI 0.890-0.988, P = 0.015) and being female (HR 10.538, 95% CI 1.375-80.793, P = 0.023) were associated with MTX-related toxicity. Toxicity occurred in approximately 30% of patients with RA and renal dysfunction receiving MTX treatment. Hydroxychloroquine use exhibited a protective effect against MTX-associated toxicity development.
关于肾功能减退患者使用甲氨蝶呤（MTX）的安全性研究有限。本研究旨在调查类风湿关节炎（RA）合并肾功能不全患者中与甲氨蝶呤（MTX）相关的毒性。这项回顾性队列研究纳入了RA合并肾功能不全的患者。肾功能不全定义为估计肾小球滤过率（eGFR）<60 mL/min/1.73 m²。我们根据肾功能不全的发病情况将患者分为两组：新发病组和既往发病组。MTX相关毒性包括肾毒性、肝毒性、严重感染、全血细胞减少、白细胞减少、血小板减少和黏膜炎。进行Cox分析以确定与毒性相关的因素。该研究纳入了120例接受MTX治疗的RA合并肾功能不全患者（66例：新发病；54例：既往发病）。eGFR中位数为52.1 mL/min/1.73 m²[四分位间距（IQR）47.1 - 57.3]。35例患者（29.2%）发生毒性反应，毒性事件发生的中位时间为23个月（IQR 10 - 57）。毒性反应分布如下：白细胞减少（10%，12/120）、肾毒性（5.8%，7/120）、肝毒性（7.5%，9/120）、严重感染（8.3%，10/120）、全血细胞减少（5.0%，6/120）、血小板减少（5.8%，7/120）和黏膜炎（5.8%，7/120）。新发病组和既往发病组的毒性发生率无显著差异[23/66（34.8%）对12/54（22.2%），P = 0.130]。多因素分析显示，使用羟氯喹（HR 0.425，95%置信区间0.212 - 0.853，P = 0.016）、基线eGFR（HR 0.938，95%置信区间0.890 - 0.988，P = 0.015）以及女性（HR 10.538，95%置信区间1.375 - 80.793，P = 0.023）与MTX相关毒性有关。接受MTX治疗的RA合并肾功能不全患者中约30%发生毒性反应。使用羟氯喹对MTX相关毒性的发生具有保护作用。
