Department of Rheumatology, St Georges University Hospitals NHS Foundation Trust, London, UK.
Institute of Medical and Biomedical Education, St George's , University of London, London, UK.
BMJ Open. 2019 May 5;9(5):e028466. doi: 10.1136/bmjopen-2018-028466.
To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure.
Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN).
Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland.
Patients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3-6 months, at 12 months and annually thereafter.
Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis.
Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit.
MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD.
在两个早期类风湿关节炎（RA）发病队列中，重点关注甲氨蝶呤（MTX）暴露，评估类风湿关节炎间质性肺病（RA-ILD）的预测因素。
多中心前瞻性早期 RA 发病队列研究；早期 RA 研究（ERAS）和早期 RA 网络（ERAN）。
二级保健，ERAS 有 9 个中心，ERAN 在英格兰、威尔士和爱尔兰有 23 个中心。
新诊断为 RA 的患者，n=2701。基线时收集了包括人口统计学、药物治疗和临床结局（包括是否存在 RA-ILD）在内的标准化数据，在 3-6 个月、12 个月和此后每年进行。
主要结果是 MTX 暴露与 RA-ILD 诊断的相关性。次要结果是人口统计学、合并症和 RA 特异性因素与 RA-ILD 诊断的相关性，以及 MTX 暴露与 RA-ILD 诊断时间的相关性。
在 92 例符合ILD 条件的病例中，39 例发生在 1578 例（2.5%）接受 MTX 治疗的病例中，53 例发生在 1114 例（4.8%）未接受 MTX 治疗的病例中。仅在接受任何常规合成疾病修饰抗风湿药物治疗后发生 RA-ILD （n=67）的 RA-ILD 病例的主要分析显示，MTX 暴露与新发 RA-ILD 无关（OR 0.85，95%CI 0.49 至 1.49，p=0.578），ILD 诊断时间延迟呈非显著趋势（OR 0.54，95%CI 0.28 至 1.06，p=0.072）。在包括 RA 诊断时存在 RA-ILD 病例（n=92）的扩展分析中，MTX 暴露与新发 RA-ILD 的风险显著降低相关（OR 0.48，95%CI 0.3 至 0.79，p=0.004）和 ILD 诊断时间延长（OR 0.41，95%CI 0.23 至 0.75，p=0.004）。与新发 RA-ILD 相关的其他独立基线因素包括 RA 发病年龄较大、吸烟史、男性、类风湿结节和从首次 RA 症状到首次门诊就诊的时间较长。
MTX 治疗与 RA-ILD 诊断风险增加无关。相反，有证据表明 MTX 可能会延迟ILD 的发病。
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