Department of Orthopedic Surgery, Japanese Red Cross Nagoya Daiichi Hospital, 3-35 Michishita, Nakamura, Nagoya, Aichi, 453-8511, Japan.
Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
Clin Rheumatol. 2023 Aug;42(8):2069-2077. doi: 10.1007/s10067-023-06639-z. Epub 2023 May 22.
Methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA). Frailty is the intermediate condition between being healthy and disabled, and can lead to negative health outcomes. Adverse events (AEs) due to RA drugs are expected to be higher in frail patients. The present study aimed to investigate the relationship between frailty and MTX discontinuation due to AEs in RA patients.
Of 538 RA patients who visited us between June and August 2020 as part of the retrospective T-FLAG study, 323 used MTX. After 2 years of follow-up, we investigated AEs leading to MTX discontinuation. Frailty was defined as a Kihon Checklist (KCL) score ≥ 8. Cox proportional hazards regression analysis was performed to identify factors associated with MTX discontinuation due to AEs.
Of the 323 RA patients (251 women, 77.7%) who used MTX, 24 (7.4%) discontinued MTX due to AEs during the 2-year follow-up period. Mean ages in the MTX continuation/discontinuation groups were 64.5 ± 13.9/68.5 ± 11.7 years (p = 0.169), Clinical Disease Activity Index was 5.6 ± 7.3/6.2 ± 6.0 (p = 0.695); KCL was 5.9 ± 4.1/9.0 ± 4.9 points (p < 0.001); and the proportion of frailty was 31.8%/58.3% (p = 0.012). MTX discontinuation due to AEs was significantly associated with frailty (hazard ratio 2.34, 95% confidence interval 1.02-5.37) even after adjusting for age and diabetes mellitus. AEs included liver dysfunction (25.0%), pneumonia (20.8%), and renal dysfunction (12.5%).
Because frailty is a significant factor contributing to MTX discontinuation due to AEs, the latter should be carefully monitored in frail RA patients who use MTX. Key Points • Of the 323 rheumatoid arthritis (RA) patients (251 women, 77.7%) who used methotrexate (MTX), 24 (7.4%) discontinued MTX due to adverse events (AEs) during the 2-year follow-up period. • MTX discontinuation due to AEs was significantly associated with frailty (hazard ratio 2.34, 95% confidence interval 1.02-5.37) even after adjusting for age and diabetes mellitus, and neither the MTX dose, folic acid supplementation, nor GC co-therapy were factors in MTX discontinuation. • Frailty is a predominant factor in MTX discontinuation among established, long-term pretreated RA patients, and the occurrence of AEs due to MTX should be carefully monitored when frail RA patients use MTX.
甲氨蝶呤（MTX）是治疗类风湿关节炎（RA）的基础药物。虚弱是健康与残疾之间的中间状态，可能导致不良健康后果。预计 RA 药物引起的不良事件（AE）在虚弱患者中更高。本研究旨在探讨 RA 患者中虚弱与 MTX 因 AE 停药之间的关系。
在 2020 年 6 月至 8 月期间作为回顾性 T-FLAG 研究的一部分，我们对 538 名就诊的 RA 患者中的 323 名使用了 MTX。经过 2 年的随访，我们调查了导致 MTX 停药的 AE。虚弱定义为 Kihon Checklist（KCL）评分≥8。采用 Cox 比例风险回归分析确定与 MTX 因 AE 停药相关的因素。
在使用 MTX 的 323 名 RA 患者（251 名女性，77.7%）中，有 24 名（7.4%）在 2 年随访期间因 AE 停用 MTX。MTX 继续/停药组的平均年龄分别为 64.5±13.9/68.5±11.7 岁（p=0.169），临床疾病活动指数为 5.6±7.3/6.2±6.0（p=0.695）；KCL 分别为 5.9±4.1/9.0±4.9 分（p<0.001）；虚弱比例分别为 31.8%/58.3%（p=0.012）。AE 导致 MTX 停药与虚弱显著相关（危险比 2.34，95%置信区间 1.02-5.37），即使在调整年龄和糖尿病后也是如此。AE 包括肝功能障碍（25.0%）、肺炎（20.8%）和肾功能障碍（12.5%）。
由于虚弱是 MTX 因 AE 停药的重要因素，因此在使用 MTX 的虚弱 RA 患者中应密切监测后者。关键点 • 在使用甲氨蝶呤（MTX）的 323 名类风湿关节炎（RA）患者（251 名女性，77.7%）中，有 24 名（7.4%）在 2 年随访期间因不良事件（AE）停用 MTX。 • 即使在调整年龄和糖尿病后，AE 导致的 MTX 停药与虚弱仍显著相关（危险比 2.34，95%置信区间 1.02-5.37），而 MTX 剂量、叶酸补充剂和 GC 联合治疗均不是 MTX 停药的因素。 • 在既定的、长期预处理的 RA 患者中，虚弱是 MTX 停药的主要因素，当虚弱的 RA 患者使用 MTX 时，应密切监测 MTX 引起的 AE。
