Risk factors for interstitial lung disease in early rheumatoid arthritis and external validation of screening strategies: Baseline results of SAIL-RA

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Abstract
Background Risk factors and screening strategies for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have received limited evaluation in patients with early RA. We investigated RA-ILD prevalence, risk factors, and the performance of proposed RA-ILD screening methodologies in a multicenter, prospective study of patients with early RA. Methods Participants with early RA, defined as being within two years of RA diagnosis, were enrolled at five US sites and assessed with high-resolution computed tomography (HRCT) chest imaging, pulmonary function tests, and autoantibodies. RA-ILD presence was determined through independent HRCT review by thoracic radiologists. We investigated RA-ILD risk factors using multivariable logistic regression and reported the predictive performance of RA-ILD screening strategies (ANCHOR-RA, 2023 ACR/CHEST, Four Factor Score, and ESPOIR). Results Among 172 participants (74% female, 82% seropositive, median RA duration 0.79 years, mean age 55.3 years), 19 (11%) had ILD on HRCT. Moderate/high RA disease activity by DAS28-ESR (OR 7.00 [1.95, 25.1]) and age ≥60 years (OR 3.87 [1.33, 11.3]) were associated with RA-ILD. Sensitivity and specificity of screening strategies ranged from 0.32-0.95 and 0.32-0.81, respectively. The number of early RA patients needing screening to detect one ILD case ranged from 3.6 to 6.4. Discussion In this prospective, multicenter study, ILD prevalence in early RA was 11%. Disease activity and older age were strongly associated with ILD in early RA, and several proposed ILD screening strategies performed showed promise for enabling ILD screening in early RA. Several risk factors for rheumatoid arthritis-associated interstitial lung disease have been identified. However, most prior studies have focused on patients with established RA. Several approaches to RA-ILD screening have been proposed, including the recent 2023 ACR/CHEST guidelines. However, none have been specifically evaluated in patients with early RA. In a multicenter, prospective cohort of patients with early RA (diagnosed within 2 years of enrollment), moderate or high RA disease activity and older age were significantly associated with evidence of interstitial lung disease on high resolution CT chest imaging. Several proposed RA-ILD screening criteria performed well in the early RA period. The simplest screening strategy included older age, male sex, and moderate/high RA disease activity and had a number needed to screen of 3.6 patients to detect one RA-ILD case. Simple screening strategies using demographic and clinical data may enable selection of early RA patients for RA-ILD screening.

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