Op0165 Difficult to Treat Rheumatoid Arthritis Incidence and Risk Factors in the Early Arthritis Uclouvain Brussels Cohort

Background: Over the past decades, the treatment of Rheumatoid Arthritis (RA) has significantly improved, making accessible therapeutic goals such as clinical and structural remission. However, a substantial number of patients show resistance to several drugs. These patients have been recently included in the definition of Difficult-to-treat (D2T) patients 1. As a new definition, research is now focusing on determining which factors may influence the resistance to multiple mechanisms of action, including patients' intrinsic characteristics. Objectives: To identify any baseline clinical features and disease characteristics associated with a D2T phenotype in a large cohort of early RA (ERA). Moreover, in a five-year follow-up, we compared the disease and treatment-related comorbidities between the D2T and the non-D2T cohorts. Methods: We performed a retrospective analysis recording clinical and laboratory data (TJC, SJC, C-Reactive Protein), patients-reported outcome (VAS, HAQ), and disease activity composite indexes (DAS28, SDAI, CDAI). Clinical data were collected for each ERA patient naïve to DMARD and fulfilling the ACR/EULAR 2010 cclassification criteria at baseline and after 6, 12, 36, and 60 months. D2T and non-D2T cohort features were compared. A logistic multivariate regression analysis was performed to confirm discriminant variables in the univariate analysis. Results: We included 391 ERA patients F/M 109/282, median age 48.2 years IQR (21.26); In a five-year follow-up, 42 patients matched the definition of D2T. When comparing D2T and non-D2T patients (Table 1A) the formers were characterized by a higher seropositivity rate for Rheumatoid Factor and ACPA (82.9% versus 63.6%; p=0.01 and 85.4% versus % 66.4; p=0.01), significantly higher baseline bone erosions (70.7% versus % 46; p=0.003) and higher baseline disease activity assessed with SDAI 31.7 (IQR 30.2) versus 24.7 (IQR 19.8); p=0.02 and CDAI 27.8 (IQR 27.2) versus 22.15 (IQR 17.9); p=0.04. No other baseline features differed between the two groups for all the items (TJC, SJC, DAS28, SDAI, and CDAI, CRP) except for TJC44 12 (17.25) versus 10(12); p=0.02 (Table 1). Discriminant variables were included in a multivariate logistic regression analysis. Baseline erosions (Y/N) were confirmed as independent predictors of evolution toward a D2T phenotype OR 2.2 (CI 1.04 - 5.2); p=0.04. During the follow-up, disease activity (DAS28, CDAI, SDAI) was consistently higher in the D2T group (Figure 1A-C) during all the observation time. After five years of follow-up (Table 1B), D2T patients more commonly suffered from infections (51.2% versus 27.5%; p=0.0015), and osteoporosis (25% versus 8.1%; p=0.005) and were exposed to a higher cumulative dose of glucocorticoids > 1 gram (52.5% versus 35.5%; p=0.035). Table 1. A) Baseline Disease Features; B) 5- Years Follow-up comorbidities Conclusion: Our results suggest that patients characterized by baseline disease features including seropositivity (RF and/or ACPA), baseline bone erosions, and disease activity are more prone to evolve into a D2T-RA. In a five-year follow-up, D2T patients received higher GC doses and more commonly developed diseases and iatrogenic-related comorbidities such as osteoporosis and infections. REFERENCES: 1 Nagy G, Roodenrijs NM, Welsing PM, et al.. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–5. 10.1136/annrheumdis-2020-217344. Acknowledgements: NIL. Disclosure of Interests: None declared.