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Distinctive Clinical Characteristics and Outcome of ILD-Onset Rheumatoid Arthritis and ACPA-Positive ILD: a Longitudinal Cohort of 282 Cases

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Abstract

The aim of this study is to investigate the clinical features and outcome of interstitial lung disease (ILD)-onset rheumatoid arthritis (RA) and anti-citrullinated protein antibody (ACPA)-positive ILD-only patients. Arthritis-onset and ILD-onset RA-ILD and ACPA-positive ILD-only patients consecutively admitted to Peking Union Medical College Hospital from January 2008 to December 2017 were enrolled and followed-up. Their demographic, clinical, and laboratory features as well as outcome were collected and analyzed. Compared with arthritis-onset RA-ILD (n = 166, median arthritis-to-ILD interval: 60 months), the ILD-onset RA-ILD (n = 75, median ILD-to-arthritis interval: 2 months) had less rheumatoid nodules and higher titer of ACPA, and manifested more stable ILD (median estimated progression-free survival: 120 vs. 100 months, p = 0.019). Elder age (≥ 65 years) at ILD diagnosis and UIP pattern were associated with ILD progression by both univariate and Cox hazards modeling analysis (p < 0.05). In ACPA-positive ILD-only patients (n = 41), arthritis developed in 7 (17.1%) female patients after a median interval of 24 months. ACPA-positive ILD who subsequently developed arthritis exhibited higher frequency of rheumatoid factor (RF), higher titer of ACPA, and higher levels of ESR and CRP (p < 0.05). Multivariate regression analysis showed that positive RF (OR 12.55, 95% CI 1.31 to 120.48) was the independent risk factor for arthritis development in ACPA-positive ILD-only patients. ILD-onset RA-ILD had more stable ILD compared with arthritis-onset RA-ILD. ACPA-positive ILD patients with positive RF are at increased risk of developing RA.

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Acknowledgments

We thank Yang-Zhong Zhou and Yan-Ping Wei for their advice and help.

Funding

This study was supported by grants from the National Natural Science Foundation of China (81788101, 81630044), Chinese Academy of Medical Science Innovation Fund for Medical Sciences (CIFMS2016-12M-1-003, 2017-12M-1-008, 2017-I2M-3-011, 2016-12M-1-008), Beijing Capital Health Development Fund (2020-2-4019), and the Construction Project of National Traditional Chinese Medicine Clinical Research Base of SATCM, and Clinical Cooperative Project of Chinese and Western Medicine for Major and Knotty Diseases of SATCM.

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Correspondence to Hua Chen or Xuan Zhang.

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The study was approved by the institutional ethical review board of Peking Union Medical College Hospital (approval number: JS-2034).

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Chen, RX., Zhao, LD., Xiao, XY. et al. Distinctive Clinical Characteristics and Outcome of ILD-Onset Rheumatoid Arthritis and ACPA-Positive ILD: a Longitudinal Cohort of 282 Cases. Clinic Rev Allerg Immunol 60, 46–54 (2021). https://doi.org/10.1007/s12016-020-08819-0

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