To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months. We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97–1.40] and 1.06 [0.86–1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35–2.57]) and log CRP (1.55 [1.21–1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings. Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient’s global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.

中文翻译：

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全身炎症和疾病活动对类风湿性关节炎患者间质性肺病发病率的影响 – 德国生物制品登记处 RABBIT 中的嵌套病例对照研究


探讨类风湿性关节炎 （RA） 患者间质性肺病 （ILD） 的发生与 RA 及其各种成分的疾病活动性之间的关联，尤其是 C 反应蛋白 （CRP） 和红细胞沉降率 （ESR）。我们分析了 2001 年至 2021 年期间在德国生物制品登记处 RABBIT 中观察到的 RA 患者的数据。在一项嵌套病例对照研究中，随访期间报告了 ILD 新发诊断的患者与无 ILD 的患者以 1：5 的比例匹配。匹配标准为性别、年龄、RA 持续时间、入组日期和观察时间。由有向无环图 （DAG） 定义，我们调整了类风湿因子、吸烟、慢性阻塞性肺病和结核病/慢性病毒感染的条件 logistic 回归模型，以研究疾病活动/全身炎症的影响。在 ILD 前 12 个月内和整个观察时间内分析平均值和分类值。此外，还进行了两项敏感性分析，仅使用经过验证的 ILD 病例，并考虑观察时间超过 12 个月的 ILD 病例。我们确定了 139 例新发 ILD 的 RA 患者，并将其与 686 例对照相匹配。在 94 例中，诊断可以得到验证，98 例随访 > 12 个月。平均 DAS28 综合评分 （包括 ESR 或 CRP） 与发生 RA-ILD 无关 （比值比分别为 1.16 [95% 置信区间： 0.97-1.40] 和 1.06 [0.86-1.29]）。然而，炎症的单一指标，对数 ESR （1.86 [1.35-2.57]） 和对数 CRP （1.55 [1.21-1.97]），与 RA-ILD 风险增加显著相关。对于持续高度炎症，ILD 的风险也更高。 其他 DAS28 成分与 RA-ILD 无显著相关性。这些结果对于患者整个观察时间和 ILD 前 12 个月内的值是一致的。敏感性分析证实了这些发现。ESR 和 CRP 表明的更高水平的全身炎症，而不是关节计数或患者的整体评估，与 RA 患者发生 ILD 的发生显著相关。作为 RA-ILD 发展的可能预测因素，应密切监测全身炎症，并且独立于关节计数结果。