Background: Rheumatoid arthritis (RA) is an autoimmune disease where autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), are associated with disease severity and clinical outcomes. This study aimed to evaluate the reduction in RF and ACPA levels at one year in RA patients treated with bDMARDs or tsDMARDs and identify baseline factors associated with these reductions and their relationship with disease activity. Methods This prospective, longitudinal study included RA patients from the Reuma-check program who initiated bDMARDs or tsDMARDs. Clinical, laboratory, and imaging evaluations were conducted at baseline and one year, including RF and ACPA levels, SDAI, and CDAI, The reduction was defined as the difference between the title at year and the basal.. Results: Of 183 enrolled patients, 110 completed one-year follow-up. ACPA and/or RF reductions were observed in 38–50%, with median decreases of 38.7 IU/mL for ACPA and 12.5 IU/mL for RF. In logistic regression the predictive factor for decrease were: diagnosis less than 12 months (p = 0.007; OR = 9), smoking (p = 0.04; OR = 3). TNF blockers independently predicted reductions in both antibodies (OR=5, p=0.022). Patients with RF or ACPA reductions had significantly lower CDAI and SDAI scores at one year. For RF, median CDAI was 6 (IQR 3–19) vs. 11 (IQR 5–22) in those without reduction (p=0.03). ACPA reductions similarly correlated with improved disease activity scores. Conclusions: Reductions in RF and ACPA occurred in nearly half of patients, correlating with improved clinical outcomes. Shorter disease duration, use of TNFb were key predictors of antibody reduction.