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Background: Rheumatoid arthritis (RA) refractory to multiple lines of treatment represents a significant problem to patients and rheumatologists. In 2020, EULAR proposed a standardized definition of difficult-to-treat (D2T) RA1. To date, most studies on D2T RA have focused on factors associated with established arthritis. Few studies have examined which factors already present in early RA could predict progression to future D2T disease. A better understanding of predictors of progression to D2T RA may aid rheumatologists in the treatment of early RA. Objectives: To identify factors present in early RA associated with progression to D2T status. Methods: In the Early Undifferentiated PolyArthritis (EUPA) study, consecutive patients with early arthritis affecting 3 or more joints for at least 1 month and less than 12 months and evaluated at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) were prospectively followed. Patients underwent predetermined visits at diagnosis and at 12, 18, 30, 42 and 60 months with a complete joint count, blood tests, and administered validated questionnaires. Patients from the EUPA study who met the 1987 and/or 2010 criteria for RA were included in the analysis. EUPA patients prescribed at least one advanced therapy are part of the University of Sherbrooke Registry of Advanced Therapies (USRAT), a long-term source of clinical and administrative data. D2T RA was defined as having started a third mechanism of action of a biologic or targeted synthetic DMARD (b/tsDMARD), or having a swollen joint count (SJC) ≥ 3 or taking prednisone ≥ 7.5mg daily 1 year after having started a second mechanism of action. Easy-to-treat (E2T) RA was defined by being treated with a sigle advanced therapy and having SJC ≤ 1 and an absence of corticosteroids 1 year after having started a first b/tsDMARD. Pre-D2T RA was defined as having failed at least 1 b/tsDMARD, but not meeting criteria for D2T RA. Demographic, clinical and treatment variables were analyzed and compared between groups with chi-square or Fisher exact test for categorical variables or with Mann-Whitney U test or Kruskal-Wallis test for continuous variables. Results: Among the 952 EUPA patients with early RA, 152 met the 1987 and/or 2010 criteria for RA and started at least one b/tsDMARD after inclusion. The median time between the onset of symptoms and the start of the first b/tsDMARD was 1.7 years (IQR 1.1 to 4.3), without significant differences between groups. Twenty-six patients were excluded due to insufficient information or duration of follow-up to meet criteria for one of the groups. Of the remaining 126 patients, 34 (27.0%) met criteria for D2T RA, 45 (35.7%) for E2T RA and 27 (21.4%) for pre-D2T. Twenty (15.9%) patients were treated with a single b/tsDMARD but did not meet E2T RA criteria at 1 year; they were included in the All non-D2T group. The mean follow-up was similar between groups: D2T 9.8 years, pre-D2T 9.1 years, E2T 9.6 years (p=0.107). At baseline inclusion in EUPA, female sex, a higher joint count, presence of erosions, pulmonary comorbidities, elevated depressive symptoms and fatigue were associated with progression to D2T when compared to E2T or to All non-D2T (Table 1). Presence of methotrexate at the time of fulfilment of criteria for each group was protective of D2T RA (Table 2). Conclusion: In our cohort, some baseline clinical and patient-related variables were already predictive of progression to D2T RA. Presence of methotrexate after the start of advanced therapy was protective of D2T RA. The identification in early RA of modifiable risk factors for D2T outcome may allow for preventive interventions. REFERENCES: 1 Nagy G, Roodenrijs NM, Welsing PM, et al. Eular definition of difficult-to-treat rheumatoid arthritis. Annals of the rheumatic diseases. 2021;80(1):31-35. doi:10.1136/annrheumdis-2020-217344. Acknowledgements: NIL. Disclosure of Interests: None declared.
Lessard et al. (Sat,) studied this question.