AB0716 PLASMA BIOMARKERS IN RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (RA-ILD): FIBROTIC VERSUS NON-FIBROTIC DISEASE (BERTHA STUDY BASELINE DATA)
Authors: L. Kawano-Dourado, K. Bonfiglioli, A. C. Medeiros-Ribeiro, L. Mota, A. Pugliesi, L. Muniz, D. Strabelli, M. Sawamura, A. Shimabuco, S. Pasoto, L. Teófilo Lourenconi, F. L F B Riscado, C. Albuquerque, T. R C M Morais, C. C Da Silva, A. C. Londe, L. C Palhares, R. Barros, L. F Marqueze, J. D R Lindenau, Y. C N Muniz, R. H V Machado, T. S Veiga, V. B Bezerra, L. O Silva, J. O Gomes, D. H K Miyada, S. M Tokunaga, T. Mendonça, B. G Baldi, A. Latini
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) presents with a high prevalence of pulmonary fibrosis. Pulmonary fibrosis confers a worse prognosis to RA-ILD. There are no well stablished serum biomarkers for the identification of fibrotic versus non-fibrotic RA-ILD. This study reports the baseline plasma biomarkers analysed in RA-ILD individuals, both with and without pulmonary fibrosis, who are being closely monitored for two years as part of the BERTHA study (NCT04136223). <h3>Objectives:</h3> Investigate whether exploratory plasma biomarkers differ between RA-ILD with and without pulmonary fibrosis. <h3>Methods:</h3> All consecutive adult RA-ILD participants seen in five Brazilian rheumatologic centers between March 2021 – July 2022 were included in the study (ethical approval n.3.799.253). Patients with mMRC dyspnea score 5, use of long-term oxygen supplementation, significant pulmonary hypertension, and comorbidities with an impact in the respiratory system were excluded. At baseline, participants underwent high resolution computed tomography (HRCT) of the chest and blood draw. HRCTs were visually assessed by two independent radiologists and quantitatively analyzed by lung densitometry (Chest Imaging Platform software). Pulmonary fibrosis was defined on visual assessment of HRCT by the unequivocal presence of traction bronchiectasis and/or honeycombing. Plasma was analyzed for known biomarkers associated with pulmonary fibrosis, namely anti-CCP, MMP-7, SP-D, CCL-8, CA125, and CA19.9. The novel biological markers, tetrahydrobiopterin (BH4) and neopterin, associated with inflammation and oxidative stress, were also assessed. All laboratory analyses were performed in a central laboratory (LABOX, Federal University of Santa Catarina). Mean differences between participants with and without pulmonary fibrosis were evaluated using a two-sample T-test or Mann-Whitney U test. <h3>Results:</h3> 95 RA-ILD participants were included (Table 1). Articular disease activity did not differ between groups. Pulmonary fibrosis was present in 84 % of participants [kappa radiologists: 0.65 (95CI 0.45-0.84)]. Patients with pulmonary fibrosis were older with worse pulmonary function (FVC % predicted 75±16 vs. 83±16, p=0.038, and DLCO %predicted 68±21 vs. 93±5, p=0.014), worse 6-minute walking distance (361±61m vs. 419±116m, p=0.023), and with more extensive disease in the HRCT (% HAA 12.3±6.8 vs. 6.6±3.8, p=0.004). No difference was observed in baseline plasma biomarkers between participants with or without pulmonary fibrosis (Table 1). <h3>Conclusion:</h3> At baseline, participants with RA-ILD and pulmonary fibrosis did not differ from RA-ILD participants without pulmonary fibrosis in terms of MMP-7, SP-D, CCL-8, CA125, and CA19.9. New plasma biomarkers, BH4 and neopterin, also did not differ between groups. As per BERTHA protocol, participants will be followed for more two years and the prognostic value of these plasma biomarkers will be assessed. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Leticia Kawano-Dourado For Boehringer Ingelheim and Roche, From Boehringer Ingelheim and Bristol-Myers-Squibb, Karina Bonfiglioli For Roche, Lilly, BMS, Ana Cristina Medeiros-Ribeiro To Roche, Lilly and BMS, Licia Mota Boehringer Ingelheim, Lilly, BMS, Alisson Pugliesi Roche, Lilly, BMS, Luciana Muniz Boehringer Ingelheim, Roche, Lilly, Daniel Strabelli: None declared, Marcio Sawamura: None declared, Andrea Shimabuco: None declared, Sandra Pasoto: None declared, Luciana Teófilo Lourenconi: None declared, Fernanda L F B Riscado: None declared, Cleandro Albuquerque: None declared, Tassiane R C M Morais: None declared, Clemilda C da Silva: None declared, Ana Carolina Londe: None declared, Luciana C Palhares: None declared, Romuel Barros: None declared, Luis F Marqueze: None declared, Juliana D R Lindenau: None declared, Yara C N Muniz: None declared, Rachel H V Machado: None declared, Thabata S Veiga: None declared, Viviane B Bezerra: None declared, Leila O Silva: None declared, Jackeline O Gomes: None declared, Debora H K Miyada: None declared, Samira M Tokunaga: None declared, Tiago Mendonça: None declared, Bruno G Baldi Boehringer and Roche, Alexandra Latini: None declared.