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. 2025 Aug:73:152729.
doi: 10.1016/j.semarthrit.2025.152729. Epub 2025 Apr 17.

Development of a prediction model for progression of rheumatoid arthritis-associated interstitial lung disease using serologic and clinical factors: The prospective KORAIL cohort

Sung Hae Chang  1 , Misti L Paudel  2 , Gregory C McDermott  2 , Qianru Zhang  3 , Sho Fukui  4 , Minuk Kim  5 , You-Jung Ha  6 , Jeong Seok Lee  7 , Sung Won Lee  8 , Chan Ho Park  9 , Ji-Won Kim  10 , Jang Woo Ha  11 , Sang Wan Chung  12 , Eun Ha Kang  6 , Yeon-Ah Lee  12 , Yong-Beom Park  11 , Jung-Yoon Choe  10 , Eun Young Lee  13 , Jeffrey A Sparks  14
Affiliations

Development of a prediction model for progression of rheumatoid arthritis-associated interstitial lung disease using serologic and clinical factors: The prospective KORAIL cohort

Sung Hae Chang et al. Semin Arthritis Rheum. 2025 Aug.

Abstract

Objective: To develop a prediction model for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression.

Methods: We investigated predictors of RA-ILD progression in the Korean RA-ILD (KORAIL) cohort, a prospective study that enrolled patients with RA meeting ACR/EULAR criteria and ILD on chest computed tomography (CT) scans and followed for 3 years. Pulmonary function tests (PFTs) and chest CT scans were conducted annually. RA-ILD progression was defined as both physiological and radiological worsening, adapted from the 2023 ATS/ERS/JRS/ALAT definition of progressive pulmonary fibrosis. Baseline factors included clinical factors and biomarkers (autoantibodies, inflammatory markers, and pulmonary damage markers).

Results: We analyzed 138 RA-ILD patients (mean age 66.4 years, 30.4 % male, 60.1 % usual interstitial pneumonia [UIP] pattern). During a median follow-up of 2.9 years, 34.8 % (n = 48) had RA-ILD progression. Baseline associations with progression included: UIP pattern, ILD extent >10 %, DLCO %pred., anti-cyclic citrullinated peptide (anti-CCP), Krebs von den Lungen-6 (KL-6), and human surfactant protein D. We developed prediction models using UIP pattern, ILD extent, DLCO % pred., and anti-CCP titer with or without serum KL-6 levels. The models had areas under the curve (AUCs) of 0.73 and 0.75, respectively. The high-risk group had a positive predictive value for progression of 85.7 %, while the low-risk group had a negative predictive value of 94.7 %.

Conclusion: In this prospective cohort, UIP pattern, ILD extent, lower DLCO, RA disease activity, anti-CCP levels, and pulmonary damage biomarkers were associated with RA-ILD progression. We developed prediction models that may be clinically useful to risk stratify once externally validated.

Keywords: Biomarkers; Interstitial lung disease; Prediction model; Progressive pulmonary fibrosis; Rheumatoid arthritis.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eun Young Lee reports financial support was provided by National Research Foundation of Korea. Misti L. Paudel reports statistical analysis was provided by National Institutes of Health. Eun Young Lee reports a relationship with Abbvie, Samsung Bioepis, Novatis Korea, Boehringer Ingelheim Korea, Janssen Korea that includes: speaking and lecture fees. Eun Young Lee reports a relationship with iMBiologis, Samsung Bioepis that includes: consulting or advisory. Jeffrey A Sparks reports a relationship with Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, Sonoma Biotherapeutics that includes: funding grants. Jeffrey A Sparks reports a relationship with AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Johnson & Johnson, Merck, MustangBio, Optum, Pfizer, ReCor, Sana, Sobi, UCB that includes: consulting or advisory. Gregory McDermott reports a relationship with Rheumatology Research Foundation Scientist Development Award that includes: funding grants. SHC acknowledges the support provided by the Soonchunhyang University Research Fund for this research If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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