POS1056 CYTOKINE ANALYSIS IN PATIENTS WITH INTERSTITIAL LUNG DISEASE ASSOCIATED WITH RHEUMATOID ARTHRITIS

Abstract

Interstitial lung disease (ILD) is the most frequent non-pleural pulmonary manifestation in rheumatoid arthritis (RA) and causes high morbidity and mortality [1-3]. Currently, there are no clinically useful serum markers for the diagnosis and prognosis of RA associated ILD (RA-ILD) [4].To identify soluble cytokines that work as biomarkers for diagnosis and prognosis in RA-ILD and explore whether there is an association between those and pulmonary progression.Observational case-control study nested in a prospective cohort of cases of patients with RA (ACR/EULAR 2010) [5] with and without ILD, paired by sex, age, and time of RA evolution. All subjects underwent pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) on the inclusion date (protocol date) and, in cases of RA-ILD, also on diagnosis of ILD. The primary variable ILD was defined according to lung biopsy or HRCT according to the American Thoracic Society/European Respiratory Criteria [6], and pulmonary progression was defined as worsening FVC >10% or DLCO >15% [4]. Inflammation variables included inflammatory activity data measured by DAS28-ESR and a cytokine multiplex including Th1/Th2 function, inflammatory cytokines, and chemokines. Other clinical, RA severity and therapeutic variables were also studied: rheumatoid factors (RF), anti-cyclic citrullinated peptide antibodies (ACPA), radiological erosions, and Health Assessment Questionnaire (HAQ) values. A descriptive analysis and two Cox regression models were performed to identify factors associated with ILD and ILD progression in RA, adjusting for time to development of ILD-RA and to ILD progression, respectively.A total of 70 subjects were included, 35 RA-ILD cases and 35 RA controls without ILD (Table 1). A higher percentage of patients with RA-ILD, compared to the rest, presented elevated RF (p=0.089) and ACPA levels (p=0.031), higher DAS28-ESR values (p=0.032), number of swollen joints (p=0.040) and worse quality of life measured by HAQ (p=0.003). The variables that were independently associated with RA-ILD in the Cox regression adjusted for time of evolution of RA (Figure 1) were DAS28-ESR of moderate-high activity (OR [95% CI], 2,474 [1,173-5,220]; p= 0.017), elevated ACPA levels (OR [95% CI], 2.905 [1.244-6.786]; p=0.014), IL-18 (OR [95% CI], 1.063 [1.002-1.127]; p=0.044), MCP1CCL2 (OR [95% CI], 1.031 [1.001-1.064]; p=0.049) and SDF1 (OR [95% CI], 1.001 [1.001-1.002]; p=0.010). In the other COX regression model adjusted for time to ILD progression, the only variable associated with progression was IL18 (OR [95% CI], 1.254 [1.074-1.465]; p=0.004).Table 1.Baseline characteristics of the study populationVARIABLERA-ILD n=35RA without ILD n=35P-valueRF+ (>10), n (%)33 (94.3)31 (88.6)0.393High RF (>60)24 (68.6)17 (48.6)0.089ACPA+ (>20), n (%)32 (91.4)31 (88.6)0.690High ACPA (>340), n (%)22 (63.0)14 (40.0)0.039Erosions, n (%)21 (60.0)19 (55.6)0.705DAS28-ESR, mean (SD)3.1 (0.9)2.6 (0.9)0.032Remission/low activity, n (%)19 (54.3)27 (77.1)0.044Moderate/high activity, n (%)16 (45.7)8 (22.9)0.044Number of swollen joints, median (IQR)0.0 (0.0-1.0)0.0 (0.0-0.0)0.040HAQ, mean (SD)1.2 (0.6)0.8 (0.6)0.003Figure 1.Cox regression analysis adjusted for time of evolution of RAPatients with RA-ILD show higher inflammatory activity than RA patients without ILD. Some cytokines are associated both with diagnosis and with a worse prognosis in patients with RA-ILD, so they could be potential biomarkers for this entity. Future studies are needed to validate these data and confirm the findings.[1] Aguilar-Hurtado MC, et al. J Clin Med. 2021 Feb;10(4)[2] Castellví I, et al. Reumatol Clin. 2022 Sep[3] Fischer A, et al. Eur Respir J. 2016 Feb;47(2):588–96[4] Nieto MA, et al. Reumatol Clin. 2022 Oct;18(8):443–52[5] Aggarwal R, et al. Arthritis Rheum. 2010 Sep;62(9):2582–91[6] Lederer DJ, et al. Am J Respir Crit Care Med. 2018 Sep;198(5):e44–68This work was supported by Youth Guarantee Aid 2020 (UMA, SNGJ5Y6–12) and PAIDI Study Group for Inflammatory Rheumatic Diseases (CTS-1034)None Declared.