<h3>Background</h3> Methotrexate (MTX) has been established as the headstone of treatment for rheumatoid arthritis (RA). However, many patients treated with oral MTX experience adverse events. For this reason, new forms have been developed, such as the subcutaneous presentation in a prefilled syringe, which improve tolerance, adherence and response to treatment. <h3>Objectives</h3> The aim of this study is to describe the effectiveness of treatment with subcutaneous MTX (SC MTX) in a prefilled syringe in a reference center for the management of patients with RA and the persistence of treatment during 5 years of follow-up. <h3>Methods</h3> Retrospective observational cohort study (1-Jan-2018 and 31-Dec-2022) in patients with RA, with more than one year of treatment with MTX SC; Patients <12 months with MTX SC and those who had concomitant biological therapies were excluded. Response to treatment was analyzed by DAS28. <h3>Results</h3> 1062 patients treated with MTX SC were analyzed. At the time of analysis, 877 patients persisted in treatment and 185 abandoned due to adverse events (17.4%). 190 received it as monotherapy, 285 in combination with other conventional DMARDs, 184 with a corticosteroid, and 218 with cDMARDs and a corticosteroid. 368 (42%) started therapy due to intolerance to the oral formulation, 20 (2.3%) received the 7.5 mg dose, 114 (13%) 10 mg and 234 (26.7%) 15 mg, while 509 patients (58%) did so to optimize the dose, 259 (29.5%) with 20mg and 250 (28.5%) with 25mg. At one year of follow-up, there was an increase in the number of patients who achieved low disease activity [573 (65.3%) remission and 139 (15.85%) low activity] and there was a decrease in patients with moderate activity and high (Figure 1). Of the 877 patients, 27.6% have remained in treatment between 12 and 24 months, 18.8% between 25 and 36, 19% between 37 and 48, and 34.5% for more than 48 months. Over the 5 years, a gradual increase in the percentage of patients achieving low disease activity is observed (Figure 2). <h3>Conclusion</h3> This study shows high effectiveness of treatment with MTX SC in patients with RA; an increase in the percentage of patients who achieved remission was observed, with low treatment abandonment rates. After 5 years of follow-up, high persistence rates are observed. This makes MTX SC an excellent alternative for patients with intolerance or insufficient response to oral MTX. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Laura Villarreal: None declared, Nicolás Gutiérrez: None declared, Pedro Rodríguez-Linares: None declared, Manuel Cardozo: None declared, Adriana Rojas-Villarraga: None declared, Pedro Santos-Moreno Speakers bureau: Abbvie, Abbott, Biopas-UCB, Bristol, Janssen, Pfizer, Roche, Sanofi, Grant/research support from: Abbvie, Abbott, Biopas-UCB, Bristol, Janssen, Pfizer, Roche, Sanofi.