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.

MLP reports stock ownership for United Health Group. NK reports grant support from AstraZeneca. PAJ reports honoraria from Bristol Myers Squibb, Boehringer Ingelheim, and AstraZeneca, and grant support from Novartis, unrelated to this work. TJD is currently a full-time employee of Sanofi and has received support from Bayer and Sanofi. PFD reports grant support from Genentech and Bristol Myers Squibb, royalties or licenses from UpToDate, Inc, and participation on a Federal Drug Administration advisory board. ZSW reports grants or contracts from Bristol-Myers Squibb, Principia/Sanofi, Amgen, royalties from the Symptom Severity Index, consulting fees from Viela Bio, Zenas BioPharma, Horizon Therapeutics, Sanofi, MedPce, BioCryst, Amgen, Nkarta Inc, Adicet Bio Therapeutics, and PPD, participation in advisory board for Sanofi, Horizon Therapeutics, Novartis, Shionogi, Otsuka/Visterra, and Amgen. He is also now an employee of Amgen but was not an employee at the time of statistical analysis for this manuscript. RSJE received grant support from Boehringer Ingelheim, and he is a confounder an equity holder of Quantitative Imaging Solutions. GRW reports grants from Boehringer Ingelheim, consultancy for Pulmonx, Janssen Pharmaceuticals, Novartis, and Vertex, and is founder and co-owner of Quantitative Imaging Solutions. MBB reports institutional grant support from Genentech and the Rheumatology Research Foundation, payment or honoraria from Medscape, the American Board of Internal Medicine, and Elsevier and leadership/fiduciary roles with the American College of Rheumatology and American Board of Rheumatology. KDD has received research support from Boehringer Ingelheim. DK reports grants or contracts from the US Department of Defense, Boehringer Ingelheim, and Merck, consulting feeds from Abbvie, Amgen, Argenx, Boehringer Ingelheim, BMS, Cabaletta, Certa, Merck, Novartis, and Fate Therapeutics, participation in a data safety monitoring board or advisory board for Abbvie. BRE has received research support and consulted with Boehringer Ingelheim. JAS has received research support from Bristol Myers Squibb and Sonoma Biotherapeutics and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Johnson & Johnson, Merck, MustangBio, Optum, Pfizer, Sana, Sobi, and ReCor unrelated to this work. Other authors report no financial disclosures.

Funding: GCM is supposed by the Rheumatology Research Foundation Scientist Development Award. TJD was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL155522). KDD is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases R01 AR077607. BRE is supported by the VA CSR&D (IK2 CX002203) and the Rheumatology Research Foundation. JAS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR080659, R01 AR077607, P30 AR070253, and P30 AR072577), National Heart, Lung, and Blood Institutes (grant number R01 HL155522), the Arthritis Foundation, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award funded by the Gordon and Llura Gund Foundation. This work was supported by a Research Support Fund grant from the Nebraska Health System and the University of Nebraska Medical Center.

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