Background/Purpose: Evidence on which risk factors predict the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) is scarce and of low scientific quality. This study examines whether several clinical and serological variables are associated with an increased risk of developing this complication.

Methods: A prospective study was performed in a cohort of patients with early RA (1987 ARA or 2010 ACR/EULAR criteria and symptom duration ≤12 months) diagnosed between 2003 and 2023. All patients underwent ILD screening at diagnosis, which included targeted anamnesis for respiratory symptoms, chest auscultation for fine “velcro-like” crackles, chest X-ray (CXR) and pulmonary function tests (PFTs) with spirometry and DLCO. A thoracic high-resolution computed tomography (HRCT) was performed in case of symptoms, crackles or alterations in CXR or PFTs. In patients without initial abnormalities, screening was repeated between the second and fifth year of follow-up. Sex, age at RA onset, smoking history and cumulative dose, rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA) variables were collected. Cumulative incidence curves (i.e. 1 minus Kaplan-Meier-estimated probability), Log-Rank test and a Cox regression model were applied to determine whether or not these variables are associated with an increased risk of ILD.

Results: One hundred and eighty-eight RA patients without known ILD were included in the study. After a median follow-up time of 10.2 years (IQR 7.0 to 15.0), 30 new cases of ILD (16.0%) were diagnosed. The risk of developing lung involvement was higher among males and in patients aged ≥60 years (unadjusted Log-Rank p-value of 0.001 and 0.024, respectively) [table 1]. Cumulative incidence curves for these two variables are displayed in figures 1 and 2, respectively. In contrast, smoking, RF and ACPA showed no statistical differences, neither when tobacco dose or antibody titre were considered (p >0.05 in all scenarios). The results of a Cox regression model including all five variables is shown in table 2. Male sex showed a hazard ratio (HR) of 3.62 (95% CI 1.44 to 9.15) for the development of ILD compared to females (p=0.006). A 10-year increase in the age at the time of RA diagnosis entailed a risk 45% higher (95% CI 1.03 to 2.04) for the development of this complication (p=0.034). Smoking, RF and ACPA also failed to show significant results in the multivariate analysis (p >0.05 in all three cases).

Conclusion: In accordance with published evidence, both male sex and older age at diagnosis are associated with a greater risk of developing ILD. However, the increased risk attributed to tobacco exposure and the presence of RF and/or ACPA, especially at high titres, has not been demonstrated in this prospective study.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-and-serological-predictors-of-interstitial-lung-disease-in-rheumatoid-arthritis-are-anti-citrullinated-protein-antibodies-truly-relevant/