<h3>Background:</h3> Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease that requires complex, interdisciplinary management. In certain instances, interventions may be uselessness, particularly when patients fit the clinical definition for "difficult-to-treat" (D2T), proposed by the European Alliance of Associations for Rheumatology (EULAR) in 2021: individuals who have failed treatment, and show clinical tendencies toward deterioration. <h3>Objectives:</h3> The aim of the present study is to describe a Colombian cohort of patients who fulfill the 2021 EULAR criteria for D2T. <h3>Methods:</h3> A retrospective, observational study was conducted in RA adult patients. We included patients that fulfilled D2T EULAR criteria (Treatment failure history, including 2 biologics with different mode of action. Symptomatic disease and clinical perception). Data were recorded from databases. Patients' disease activity (DAS28, RAPID3 and PAS) and functional capacity (MDHAQ) were analyzed. Disease management was described. Measures of central tendency (MCT) and dispersion were used after assessing normality with Kolmogorov-Smirnov test (KST) to describe numerical variables. Categorical variables are described through percentages. <h3>Results:</h3> A total of 38 patients were included in the study. The mean age was 60.68 years with a standard deviation (SD) 9.2. The average disease duration was 18.5 years (SD 9.8). Notably, 39.4% (15) of patients exhibited erosions in hands. Seropositivity was observed in 76.3% (29) for rheumatoid factor and 78.9% (30) for anti-cyclic citrullinated. Regarding comorbidities, 47.3% (18/38) had arterial hypertension, 26% (10) had osteoarthrosis, 21% (8) had osteoporosis without pathological fracture, 15.7% (6/38) were diabetic mellitus type 2, and 10.5% (4) had fibromyalgia. Additionally, 5 patients had polyautoimmunity, 1 had primary biliary cirrhosis and 4 having Sjögren's syndrome. From a paraclinical perspective, the average leukocyte count was 6771 (SD 1679), mean hemoglobin was 14.04 (SD 1.4), and average creatinine was 0.73 (SD 0.18). The median CRP was 6 with an interquartile range of 5.7, and the mean ESR was 30.5 (SD 21.14). In terms of clinimetric, patients' disease activity with DAS28-ESR was 4.05 (SD 0.83), MDHAQ mean was 0.57 (SD 0.58), RAPID 3 average was 13.94 (SD 4.55), and PAS average was 3.69 (SD 1.91). Remarkably, only 1 patient (2.6%) experienced work incapacity due to the underlying disease. In terms of treatment, initial biologics included anti-TNF (44.7%, 17/38), JAK inhibitors (21%, 8/38), anti-CTLA4 (15.7%, 6/38), anti-IL-6 (13.1%, 5/38), and anti-CD20 (5.2%, 2/38). Among those initially on anti-TNF, 52.9% (9/17) switched to anti-CTLA4, 29% (5/17) to anti-CD20, and 17.6% (3/17) to anti-IL-6. For JAK inhibitors, 62.5% (5/8) switched to anti-TNF and 37.5% (3/8) to anti-CTLA-4. Regarding anti-CTLA4, 33.3% (2/6) switched to anti-TNF, 50% (3/6) to anti-IL-6, and 16.7% (1/6) to JAK inhibitors. Among those initially on anti-IL-6, 40% (2/5) switched to anti-CTLA4, 40% (2/5) to anti-TNF, and 20% (1/5) to JAK inhibitors. The two patients on anti-CD20 switched to anti-IL6 (Figure 1). Combination therapy included methotrexate (31.5%, 12/38), other csDMARDs (81.5%, 31/38), and glucocorticoids (86.8%, 33/38). <h3>Conclusion:</h3> Describing a D2T population in Latin America is essential for designing studies that critically evaluate patients experiencing failure across multiple lines of treatment. This, in turn, enables the development of innovative strategies aimed at mitigating the impact of the disease. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Pedro Santos-Moreno Abbvie, Abbott, Biopas-UCB, Bristol, Janssen, Pfizer, Roche, Sanofi, Abbvie, Abbott, Biopas-UCB, Bristol, Janssen, Pfizer, Roche, Sanofi, Gabriel-Santiago Rodríguez-Vargas: None declared, Nicolás Gutiérrez: None declared, Laura Villarreal: None declared, Fernando Rodriguez-Florido: None declared, Pedro Rodríguez-Linares: None declared, Adriana Rojas-Villarraga: None declared.