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OBJECTIVE: To evaluate the effectiveness and safety of anti-tumor necrosis factor (anti-TNF) therapies in rheumatoid arthritis (RA), and to identify the factors involved in this response. METHODS: Dynamic prospective cohort study of patients with RA treated with anti-TNF under clinical practice conditions. Effectiveness was evaluated using Disease Activity Score (DAS) 28, European League Against Rheumatism (EULAR) response, Health Assessment Questionnaire (HAQ), and time to treatment failure. Prior adherence was evaluated retrospectively and safety was evaluated by adverse events (AE). The analysis was restricted to anti-TNF-naive patients. RESULTS: The study included 161 patients treated for RA during 6 years (60 infliximab, 79 etanercept, and 22 adalimumab). At 6 months, 15% reached a good EULAR response and 38% a moderate response. A mean decrease of -1.5 (p < 0.0001) was observed in the DAS28 and of -0.34 in the HAQ (p < 0.0001); however, women showed poorer progress in terms of DAS and HAQ. In the first year, 64.3% did not experience treatment failure and this figure was 50.5% after 2 years. In one-third, glucocorticoids were withdrawn and in the remainder the dose was reduced by 50%. Adherence to treatment, selection of etanercept, and intensification of infliximab were associated with a lower probability of premature failure in the multivariate model. AE were similar to other those in studies and no outstanding differences in safety were found between the 3 anti-TNF therapies. CONCLUSIONS: Anti-TNF treatments are effective and safe, reducing the activity of the disease, disability, and the need for corticosteroids. Patients who displayed good adherence prior to the anti-TNF treatment and were treated with etanercept or with increasing doses of infliximab had the best chance of displaying a response.