POS0581 INTERSTITIAL LUNG DISEASE IN ANTI-U1RNP SYSTEMIC SCLEROSIS PATIENTS: UPDATED RESULTS FROM THE EUROPEAN SCLERODERMA TRIALS AND RESEARCH (EUSTAR) DATABASE

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Background: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis of the skin and internal organs, with interstitial lung disease (SSc-ILD) being a prevalent and significant complication. ILD is associated with high morbidity and is a leading cause of mortality in SSc patients. The prevalence of SSc-ILD, detected via high-resolution chest computed tomography (HRCT), varies from 22% to 84% [1]. Various factors such as male gender, ethnicity, the diffuse cutaneous disease subset, and anti-topoisomerase I positivity have been associated with increased risk for SSc-ILD [2, 3]. Anti-U1RNP autoantibodies, while common in mixed connective tissue disease (MCTD), are also present in SSc patients and have been linked to more severe and early disease onset, including a higher prevalence of ILD [4, 5]. However, the specific relationship between anti-U1RNP positivity and SSc-ILD has not been fully explored in large multicenter studies. This study aimed to evaluate the clinical features and prognostic potential of anti-U1RNP in SSc-ILD patients using data from the European Scleroderma Trials and Research (EUSTAR) database. Objectives: The objective of this study was to investigate the clinical associations and prognostic value of anti-U1RNP autoantibodies in SSc-ILD, using a large cohort from the EUSTAR database. Methods: Post hoc analyses were performed on patient data collected prospectively from the EUSTAR database, which includes SSc patients with documented ILD confirmed by HRCT or chest X-ray. Patients who fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for SSc were included. Anti-U1RNP positivity was determined by local testing practices, and patients were considered positive if they tested positive for anti-U1RNP at least once during the baseline or follow-up. Clinical variables, including age, sex, smoking status, disease duration, skin involvement, pulmonary function, and HRCT findings, were compared between anti-U1RNP positive and negative SSc-ILD patients. The primary outcome was the progression of ILD, measured by changes in forced vital capacity (FVC%) over a 36-month period. Patients were divided into groups based on their yearly FVC% changes: stable (≤4%), moderate (5-9%), and major progression (≥10%). Results: Out of 6043 SSc-ILD patients from the EUSTAR database, 327 (5.4%) were positive for anti-U1RNP. These patients were younger (50.8 ± 15.1 vs 57.1 ± 13.3 years, p<0.001) and had a higher frequency of non-Caucasian ethnicity (25.3% vs 5.0%, p<0.001). Anti-U1RNP positive patients also exhibited higher rates of limited cutaneous involvement, joint synovitis, and myositis compared to anti-U1RNP negative patients. At baseline, anti-U1RNP positive patients had lower FVC% (82.0% vs 86.0%, p<0.001) and DLCO% (57.0% vs 60.5%, p=0.003). Regarding ILD progression, at the 1-year follow-up, 8.6% of anti-U1RNP positive patients exhibited major FVC decline (≥10%), compared to 12.6% of anti-U1RNP negative patients (p=0.286). At 3 years, among the anti-U1RNP positive patients, there were 6 periods of major FVC decline out of a total of 75 periods (8.0%), while the anti-U1RNP negative patients experienced 282 periods of major FVC decline out of a total of 2400 periods (11.8%) (Figure 1). This difference was not statistically significant (p=0.46). There were no significant differences in the progression of ILD between double-positive (anti-U1RNP and anti-topoisomerase I or anti-centromere) and single-positive patients. Mortality rates were also similar between the groups, with 4.4% of anti-U1RNP positive patients dying during the 3-year follow-up period, compared to 6.6% of anti-U1RNP negative patients (p=0.519). Conclusion: In this large cohort from the EUSTAR database, anti-U1RNP positivity in SSc-ILD patients was associated with younger age, non-Caucasian ethnicity, and more severe baseline pulmonary dysfunction, but was not significantly associated with the progression of ILD or with mortality over a 3-year period. These findings suggest that while anti-U1RNP positivity is associated with certain clinical features in SSc-ILD, it does not appear to be associated with an increased risk of progressive lung disease compared to anti-U1RNP negative patients. Further research is needed to explore the role of anti-U1RNP as a prognostic marker in SSc-ILD. REFERENCES: [1] Distler O, Assassi S, Cottin V, Cutolo M, Danoff SK, Denton CP, et al. Predictors of progression in systemic sclerosis patients with interstitial lung disease. Eur Respir J. 2020;55(5):1902026. [2] Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG, et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol Hoboken NJ. 2014;66(6):1625–35. [3] Hussein H, Lee P, Chau C, Johnson SR. The effect of male sex on survival in systemic sclerosis. J Rheumatol. 2014;41(11):2193–200. [4] Ihn H, Yamane K, Yazawa N, Kubo M, Fujimoto M, Sato S, et al. Distribution and antigen specificity of anti-U1RNP antibodies in patients with systemic sclerosis. Clin Exp Immunol.1999;117(2):383–7. [5] Boleto G, Reiseter S, Hoffmann-Vold AM, Mirouse A, Cacoub P, Matucci-Cerinic M, et al. The phenotype of mixed connective tissue disease patients having associated interstitial lung disease. Semin Arthritis Rheum. 2023;63:152258. Figure 1Periods of FVC changes during 36±6 months follow-up among systemic sclerosis-associated interstitial lung disease patients with anti-RNP positive and anti-U1RNP negative autoantibodies in the EUSTAR database (percentage of patients per category). Acknowledgements: NIL . Disclosure of Interests: Gonçalo Boleto: None declared, Corrado Campochiaro: None declared, Oliver Distler 4P-Pharma, Abbvie, Acceleron, Acepodia Biotech, Alcimed, Altavant, Amgen, AnaMar, Aera, Argenx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Calluna (Arxx), Cantargia AB, Catalyze Capital, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, MSD Merck, Miltenyi Biotec, Mitsubishi Tanabe, Nkarta Inc., Novartis, Orion, Pilan, Prometheus, Quell, Redxpharma, Roivant, EMD Serono, Topadur and UCB, 4P-Pharma, Abbvie, Acceleron, Acepodia Biotech, Alcimed, Altavant, Amgen, AnaMar, Aera, Argenx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Calluna (Arxx), Cantargia AB, Catalyze Capital, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, MSD Merck, Miltenyi Biotec, Mitsubishi Tanabe, Nkarta Inc., Novartis, Orion, Pilan, Prometheus, Quell, Redxpharma, Roivant, EMD Serono, Topadur and UCB, 4P-Pharma, Abbvie, Acceleron, Acepodia Biotech, Alcimed, Altavant, Amgen, AnaMar, Aera, Argenx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Calluna (Arxx), Cantargia AB, Catalyze Capital, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, MSD Merck, Miltenyi Biotec, Mitsubishi Tanabe, Nkarta Inc., Novartis, Orion, Pilan, Prometheus, Quell, Redxpharma, Roivant, EMD Serono, Topadur and UCB, Andra Bălănescu Abbvie, Amgen, AlphaSigma, Astra-Zeneca, Angellini, Biogen, BMS, Berlin-Chemie, Boerhringer-Ingelheim, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Teva, UCB, Zentiva, Akros, Abbvie, Amgen, AlphaSigma, Biogen, Boehringer-Ingelheim, Lilly, Mylan, MSD, Novartis, Pfizer, Roche, Sandoz, Sobi, UCB, David Launay Shire, BioCryst; consulting fees from Astra-Zeneca, CSL Behring, and Takeda; speaker fees from BioCryst, Astra-Zeneca, CSL Behring, and Takeda, Christina Bergmann: None declared, Paolo Airo' Bohringer Ingelheim, Bohringer Ingelheim, Fahrettin Oksel: None declared, Ana Maria Gheorghiu Boehringer Ingelheim, Sandoz, Novartis, Abbvie, Ewopharma and research grants from Foundation for Research in Rheumatology (FOREUM), Boehringer Ingelheim, Sandoz, Novartis, Abbvie, Ewopharma and research grants from Foundation for Res

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