POS0348 PHENOTYPIC STRATIFICATION AND LONG-TERM OUTCOME OF PRIMARY SJÖGREN’S SYNDROME-RELATED INTERSTITIAL LUNG DISEASE
Authors: G. La Rocca, F. Ferro, E. Elefante, G. Fulvio, S. Fonzetti, I. C. Navarro García, F. D’alessandro, C. Romei, M. Mosca, C. Baldini
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Literature data regarding clinical characteristics and outcome of primary Sjögren's syndrome-related Interstitial Lung Disease (pSS-ILD) are often conflicting, possibly due to the existence of heterogeneous pSS-ILD phenotypes that still need appropriate stratification. Preliminary findings suggest that patients diagnosed with ILD during pSS course (ILD-<i>incident</i>) may present significant differences compared to those with ILD diagnosis preceding or accompanying pSS diagnosis (ILD-<i>onset</i>). <h3>Objectives:</h3> To describe the clinical features and long-term outcome of distinct pSS-ILD phenotypes. <h3>Methods:</h3> Demographic, clinical, laboratory and imaging data of consecutive pSS patients (2016 ACR/EULAR classification criteria) attending our center from Jan 2016 to Sep 2023 were retrospectively analyzed. All enrolled pSS patients were screened for ILD by clinical examination and at least one among Chest X-Ray, Pulmonary Function Tests and HRCT. All pSS-ILD diagnosis were confirmed based on clinical history, pulmonary function tests (PFT) and HRCT scans, reviewed by an expert thoracic radiologist. She also defined ILD radiologic pattern according to ATS/ERS definitions and ILD extension and severity by Warrick score. <h3>Results:</h3> Out of 474 pSS patients, 43 were classified as pSS-ILD (M:F=6:37, mean age 64 years), accounting for an overall ILD prevalence of 9.1%. 19 subjects presented ILD as the first manifestation of pSS (<i>ILD-onset</i>), while 24 developed ILD after pSS diagnosis (ILD-<i>incident</i>). Most pSS-ILD patients were symptomatic for exertional dyspnea (81.4%) and chronic cough (74.4%), with a median FVC at baseline of 87% (IQ 77-101) and median DLCO of 66% (IQ 60-76). ILD pattern on HRCT was defined as NSIP in 17 (39.5%), UIP in 8 (18.6%), OP in 2 (4.7%), LIP in 6 (14%), NSIP+OP in 8 (18.6%) and Not classifiable in 2 (4.7%) cases. 8/43 (65%) patients were treated with steroids and 20/43 (46%) received at least one immunosuppressive agent, none was treated with antifibrotics. After a median FU of 7 yrs (IQ 4-15), 8/43 (18.6%) patients necessitated long term oxygen supplementation (LTOT), while 3/43 (7%) died because of progression of the pulmonary disease. UIP patients were the oldest both at pSS diagnosis (mean age 66.3 ±10.6 yrs, p=.001) and at ILD diagnosis (mean age 70.3 ±5.4 yrs, p=.002) and exhibited the highest Warrick score (mean 21.7 ±5.5, p=.044). In contrast, compared to other ILD patients, LIP patients were the youngest at the time of pSS diagnosis (mean age 39.2±21 yrs, p=.008) and presented significantly more often constitutional symptoms (p=.017), purpura (p=.014), hypergammaglobulinemia (p=.023), triple positivity for anti-Ro60/52/SSB (p=.028) and positive RF (p=.006). Moreover, mean latency between onset of respiratory symptoms and ILD diagnosis was significantly longer for LIP patients (p=.02). Compared to ILD-<i>onset</i>, ILD-<i>incident</i> patients presented more often pSS-related hematologic abnormalities (p=.012), cutaneous involvement (p=.027), inflammatory arthralgias (p=.026), C4 hypocomplementemia (p=.012) and positive RF (p=.031). On the contrary ILD-<i>onset</i> patients tended to be more frequently of male sex (26.3% vs 4.2%, p=.07), were significantly older at pSS diagnosis (p=.008) and presented more severe fibrosis on HRCT (mean Warrick score 17.9±7.1 vs 11±5.2, p=.008). In the survival analysis male gender (p=.049) and age older than 60yrs (p=.05) at diagnosis were risk factors for mortality, while UIP pattern and ILD-<i>onset</i> of pSS were the only independent risk factors for LTOT. <h3>Conclusion:</h3> PSS-ILD patients are heterogeneous for clinical course and outcome. A UIP pattern and ILD-<i>onset</i> represent risk factors for pSS-ILD progression despite management with immunosuppressive drugs and identify a subset of patients that may benefit from additional treatment with antifibrotics. A LIP pattern seems associated with a specific phenotype of pSS, characterized by younger age at diagnosis, high systemic disease activity and serologic biomarkers of lymphocytic hyperactivation, which may represent a promising therapeutic target. Phenotypic stratification of pSS-ILD patients is crucial both for research purposes and clinical practice. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>