Steno Diabetes Center Copenhagen, Capital Healthcare Region, Gentofte, Denmark.
Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark.
Rheumatology (Oxford). 2021 Jan 5;60(1):346-352. doi: 10.1093/rheumatology/keaa327.
MTX is the most commonly recommended DMARD for first-line treatment of RA, however, it has been hypothesized to cause lung disease as an adverse effect. We investigated the risk of interstitial lung disease (ILD) and acute and chronic respiratory failure in persons with RA treated with MTX and other medications.
From the Danish National Patient Register (NPR) and the DANBIO register for rheumatic diseases, we retrieved data on 30 512 persons with RA registered in 1997-2015. Information on ILD and respiratory failure was obtained from the NPR. Information on age and sex for all Danish citizens was obtained from the Danish Civil Registration System. MTX and other medication purchases were retrieved from the Danish Prescription Registry. Associations between MTX and lung disease outcomes were analysed in Cox regression models with adjustment for age, calendar time, sex and other medications. Standardized incidence ratios (SIRs) of lung disease were calculated to compare the RA population with the general population.
There was no increased risk of lung disease with MTX treatment [one or more purchases compared with no purchases; HR 1.00 (95% CI 0.78, 1.27) for ILD and 0.54 (95% CI 0.43, 0.67) for respiratory failure] at the 5 year follow-up. The SIR was three to four times higher for ILD in MTX-treated persons with RA, but similar to the whole RA population compared with the background population.
Persons with RA had an increased risk of ILD compared with the general population, but there was no further increased risk associated with MTX treatment.
甲氨蝶呤（MTX）是治疗类风湿关节炎（RA）的一线推荐药物，但有假说认为它会引起肺部疾病等不良反应。本研究旨在调查 MTX 与其他药物治疗 RA 患者发生间质性肺病（ILD）和急性、慢性呼吸衰竭的风险。
我们从丹麦全国患者登记处（NPR）和风湿病 DANBIO 登记处获取了 1997 年至 2015 年间登记的 30512 名 RA 患者的数据。ILD 和呼吸衰竭的信息来自 NPR。所有丹麦公民的年龄和性别信息来自丹麦民事登记系统。MTX 和其他药物的购买信息来自丹麦处方登记处。使用 Cox 回归模型对 MTX 与肺部疾病结局之间的相关性进行分析，调整年龄、日历时间、性别和其他药物等因素。通过标准化发病比（SIR）来比较 RA 人群与一般人群的肺部疾病发病率。
在 5 年随访期间，与未使用 MTX 相比，使用 MTX 治疗的患者肺部疾病风险没有增加[一个或多个疗程；ILD 的 HR 为 1.00（95%CI 0.78，1.27），呼吸衰竭的 HR 为 0.54（95%CI 0.43，0.67）]。在接受 MTX 治疗的 RA 患者中，ILD 的 SIR 为 3 至 4 倍，但与整个 RA 人群相比，ILD 发病率与背景人群相似。
与一般人群相比，RA 患者发生 ILD 的风险增加，但与 MTX 治疗相关的风险没有进一步增加。
