POS0825 SEX DISPARITIES IN THE PHENOTYPE AT DIAGNOSIS OF SJÖGREN DISEASE: A GENERATIVE AI-DRIVEN CHARACTERIZATION IN 17,416 PATIENTS

Background: Although Sjögren disease (SjD) predominantly affects females, the characterization of early disease presentation in males remains understudied, hindering a comprehensive understanding of how sex may influence initial disease expression. Under-recognition of sex disparities in the disease presentation at diagnosis continues to pose a challenge, particularly because previous studies have included very small samples of male patients Objectives: To investigate the extent to which sex disparities in initial disease severity and immunological patterns in male patients with SjD are under-recognized, and how men may present a distinct phenotype at diagnosis compared to women. Methods: This study was based on a cross-sectional analysis of an anonymized dataset comprising 17,416 worldwide patients fulfilling the 2002/2016 classification criteria (Sjögren Big Data Registry). The data set variables covered demographic, clinical, and laboratory data collected at the time of diagnosis. Numerical variables were examined for distribution, central tendency, and variability, whereas categorical variables were evaluated through frequency distributions. We stratified the dataset by sex and conducted a comparative analysis of baseline glandular and systemic involvement, organ-specific ESSDAI domains, and immunological profiles. Differences between male and female groups were assessed using Student's t-tests for numerical data and Chi-square test for categorical data. Multivariate logistic regression models were developed, adjusting for epidemiological confounders (age and ethnicity) to identify predictors of sex classification. An ordinal analysis was performed to evaluate the association between sex and disease severity (using DAS categories -low, moderate and high activity-). We used a generative AI (OpenAI's GPT-4o model) environment used Python (version 3.9) with pandas (1.4.3), numpy (1.21.5), and matplotlib (3.5.1) libraries. All analyses adhered to GDPR standards, with anonymized patient data and strictly controlled secure environments. Results: The cohort included 1,161 (6.67%) men and 16,255 (93.33%) women, with a mean age at diagnosis of 51.60 years (SD = 14.50). Men showed a higher mean age at diagnosis (54.10 vs. 51.42 years in women; t=6.08, p < 0.0001) and a higher average ESSDAI score (7.65 vs. 5.93; t=7.91, p < 0.0001). Male patients also showed higher frequencies in severe DAS categories (i.e., high activity 20% vs 12% in women, χ² = 81.15, p < 0.0001). Stratification by sex identified seven statistically significant SjD-related variables: ocular dryness (p<0.001), oral dryness (p<0.001), oral diagnostic tests (p<0.001), anti-La antibodies (p=0.007), positive RF (p=0.04), cryoglobulins (p=0.049), and the glandular (p<0.001), articular (p=0.01), lymphadenopathy (p<0.001), pulmonary (p<0.001), muscular (p=0.007), peripheral nerve (p<0.001) and CNS (p=0.037) ESSDAI domains. The epidemiologically-adjusted logistic regression model (pseudo R-squared value of 0.026) identified statistical significance for age (coefficient =0.011, p=0.009; each additional year in age increased the likelihood of being female by 1.4%), ethnicity (coefficient=0.550, OR=2.77, p=0.006), ocular dryness (coefficient=-0.681, OR=3.65, p<0.001), and systemic activity in the glandular (coefficient=0.353, OR=2.67, p=0.008) and pulmonary (coefficient=0.380, OR=1.99, p=0.046) ESSDAI domains (Figure 1). Figure 1 Conclusion: This study, which included nearly 1200 male patients with SjD, provides compelling evidence underscoring the need for sex-specific considerations in diagnosis and management. Clinicians should be aware that certain features of Sjögren's syndrome may present differently in males and females, which could influence both the timing of diagnosis and the selection of appropriate therapeutic interventions. Male patients with SjD may experience more pronounced disease activity at diagnosis, potentially necessitating more intensive monitoring and tailored management strategies. REFERENCES: NIL . Acknowledgements: Sjogren's disease Gender differences in autoimmune disorders Sex disparities in Sjögren disease. Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.