Risk factors for interstitial lung disease in early rheumatoid arthritis and external validation of screening strategies: a cross-sectional analysis of the prospective SAIL-RA cohort in the USA.

Abstract

Evaluation of risk factors and screening strategies for rheumatoid arthritis-associated interstitial lung disease (ILD) in patients with early rheumatoid arthritis has been scarce. We investigated the prevalence of rheumatoid arthritis-associated ILD, risk factors, and the performance of proposed screening methods for rheumatoid arthritis-associated ILD in patients with early rheumatoid arthritis. We performed a cross-sectional analysis of the prospective Study of Inflammatory Arthritis and Interstitial Lung Disease in Early RA (SAIL-RA). Study participants were eligible for inclusion if diagnosed with early rheumatoid arthritis, defined as being within 2 years of a diagnosis. Exclusions were pregnancy at enrolment or inability or unwillingness to obtain high-resolution CT (HRCT) chest imaging. Participants were enrolled at five academic health-care centres in the USA and assessed through surveys, medical history, HRCT chest imaging, pulmonary function tests, and laboratory testing for autoantibodies. Rheumatoid arthritis-associated ILD was identified through independent review of HRCTs by thoracic radiologists. We investigated risk factors for rheumatoid arthritis-associated ILD using multivariable logistic regression and reported the predictive performance of screening strategies for rheumatoid arthritis-associated ILD (from the ANCHOR-RA study; the 2023 guidelines from the American College of Rheumatology and American College of Chest Physicians [ACR-CHEST]; a four-factor risk score proposed in 2023; Sociedad Española de Reumatología and Sociedad Española de Neumología y Cirugía Torácica criteria; criteria proposed by Paulin and colleagues; and criteria derived from the ESPOIR cohort). The primary outcome was the presence of rheumatoid arthritis-associated ILD. Participants were recruited between May 1, 2017, and Feb 22, 2024. Of 191 patients who were assessed for eligibility and included in the SAIL-RA cohort, 172 completed HRCT chest imaging and were included in this analysis: 128 (74%) were female, 44 (26%) were male, mean age was 55·3 years (SD 13·7), 126 (74%) of 171 were anti-cyclic citrullinated peptide (CCP) positive, 116 (68%) of 170 were rheumatoid factor positive, and median rheumatoid arthritis duration was 0·79 years (IQR 0·36-1·60); 19 (11%) had rheumatoid arthritis-associated ILD on HRCT. Factors associated with rheumatoid arthritis-associated ILD included moderate or high rheumatoid arthritis disease activity, determined by Disease Activity Score using 28 joints with erythrocyte sedimentation rate more than or equal to 3·2 (adjusted odds ratio [aOR] 7·00 [95% CI 1·95-25·13] vs remission or low disease activity) and age of 60 years or older (aOR 3·87 [1·33-11·27] vs age <60 years). Sensitivity of screening strategies ranged from 0·05 (95% CI 0·00-0·15) with the Paulin criteria (four-point cutoff) to 1·00 (0·97-1·00) with both the ANCHOR-RA and ACR-CHEST criteria (one-factor cutoff), and specificity ranged from 0·11 (0·06-0·16) with the ACR-CHEST criteria (one-factor cutoff) to 0·97 (0·95-1·0) with the Paulin criteria (four-point cutoff). The number of patients with early rheumatoid arthritis who needed to be screened to detect one case of rheumatoid arthritis-associated ILD ranged from 3·6 for the ESPOIR criteria (two-factor cutoff) to 7·7. In this population with early rheumatoid arthritis, 11% had rheumatoid arthritis-associated ILD. Moderate or high disease activity and age of 60 years or older were strongly associated with rheumatoid arthritis-associated ILD in early rheumatoid arthritis. Several proposed screening strategies using factors routinely available at the point of care showed promise for detecting rheumatoid arthritis-associated ILD in early rheumatoid arthritis. National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Conditions, Rheumatology Research Foundation, University of Nebraska Medical Center, and University of Nebraska Health System.