Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts
Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts
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DOI：
10.1136/bmjopen-2018-028466
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发表时间：
2019-05-01
期刊：
影响因子：
2.9
通讯作者：
Young, A.
中科院分区：
文献类型：
--
作者：
Kiely, Patrick;Busby, A. D.;Young, A.
目的 评估两个早期类风湿性关节炎 (RA) 起始队列中类风湿性关节炎间质性肺疾病 (RA-ILD) 的预测因素，重点关注甲氨蝶呤 (MTX) 暴露。设计多中心前瞻性早期 RA 起始队列研究；早期 RA 研究 (ERAS) 和早期 RA 网络 (ERAN)。设置二级护理，ERAS 9 个中心，ERAN 23 个中心位于英格兰、威尔士和爱尔兰。参与者新诊断 RA 的患者，n=2701。在基线、3-6 个月内、12 个月以及此后每年收集标准化数据，包括人口统计、药物治疗和临床结果（包括 RA-ILD 的存在）。 主要和次要结果测量 主要结果是 MTX 暴露与 RA-ILD 诊断之间的关联。次要结局是人口统计学、共病和 RA 特异性因素与 RA-ILD 诊断的关联，以及按时暴露 MTX 与 RA-ILD 诊断的关联。 结果 在 92 例符合条件的 ILD 病例中，1578 例（2.5%）MTX 暴露病例中有 39 例发生，1114 例（4.8%）非 MTX 暴露病例中有 53 例发生。对仅在任何传统合成缓解病情抗风湿药物治疗后才发生的 RA-ILD 病例的初步分析 (n=67) 显示，MTX 暴露与 RA-ILD 事件无关（OR 0.85，95% CI 0.49 至 1.49，p=0.578），延迟 ILD 诊断的趋势不显着（OR 0.54，95% CI 0.28 至1.06，p=0.072）。在一项包括 RA 诊断时出现的 RA-ILD 病例 (n=92) 的扩展分析中，MTX 暴露与 RA-ILD 事件风险显着降低（OR 0.48，95% CI 0.3 至 0.79，p=0.004）和 ILD 诊断时间延长相关（OR 0.41，95% CI 0.23 至 0.75，p=0.004）。与 RA-ILD 事件相关的其他独立基线包括 RA 发病年龄较高、曾经吸烟、男性、类风湿结节以及从首次 RA 症状到首次门诊就诊的时间较长。 结论 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 的发作。
Objectives 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.Design Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN).Setting Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland.Participants 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 and secondary outcome measures 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.Results 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 nonsignificant 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.Conclusions 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.