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Objective: To describe disease-modifying antirheumatic drug (DMARD) patterns in routine clinical practice in adult rheumatoid arthritis (RA) patients and to ascertain the reasons for methotrexate (MTX) discontinuation. Methods: A cross-sectional observational study was conducted from March to October 2014 at the Rheumatology Units of seven hospitals in Spain. In a single visit, the treating rheumatologist completed an online case report form. This report contained sociodemographic and RA variables. This study was conducted in accordance with Good Clinical Practice and local and national research legislations. Results: A total of 301 patients (71% women) with a mean age of 56.7±14.0 years and disease duration of 3.6±1.5 years were examined. The patients had RA with moderate disease activity, at least one poor prognostic factor, and comorbidities. The mean time between RA diagnosis and prescription of the first conventional synthetic DMARD (csDMARD) was 2.4±6.0 months. A total of 295 patients (98%) started the first csDMARD on monotherapy. MTX was the most-prescribed first-line drug (n=233, 79%). The mean treatment time of the first-line csDMARD was 27.0±19.4 months. Of these patients, 98% progressed to a second-line csDMARD; 118 patients were changed to another DMARD, mainly due to inefficacy (51, 37%), adverse events (AEs, 37, 27%), or intolerance (18, 13%). The use of MTX as second-line therapy reduced from 79% to 51%. At the time of the study, 200 patients (66%) received a csDMARD as monotherapy and 45 (15%) a combination of =2 csDMARDs. Fifty-five (18%) patients were being treated with a biological drug in monotherapy (16, 29%) or in a combination with a csDMARD (39, 71%), mainly MTX, 147 patients (57%) received steroids. Biological DMARD were prescribed as the second line for 42% of patients and 51% of patients received the third-line therapy or beyond. The rate of AEs that motivated a change in the csDMARD was 34%. Conclusion: MTX was the most-used csDMARD as first and second-line therapy together with corticosteroids. The combination of two or more csDMARDs as first-line treatment was very infrequent. MTX toxicity and intolerance were higher and more significant than inefficacy but progressively decreased with use. [ABSTRACT FROM AUTHOR]