Objective.To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)–tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission.Methods.The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study. MBDA scores and ACPA status were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and direct treatment costs were evaluated every 3 months. MBDA and ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates.Results.RA patients with a low MBDA score (< 30 units) and negative ACPA showed the lowest relapse risk (19%), while double-positive patients showed high relapse risk (61%). In ACPA-negative and MBDA-negative (< 30 units), and ACPA or MBDA single-positive (> 30 units) groups, DMARD tapering appears feasible. Considering only patients without flare, direct costs for synthetic and biologic DMARD in the ACPA/MBDA-negative and single positive groups (n = 41) would have been €372,245.16 for full-dose treatment over 1 year. Tapering and stopping DMARD in this low-risk relapse group allowed a reduction of €219,712.03 of DMARD costs. Average reduction of DMARD costs per patient was €5358.83.Conclusion.Combining MBDA score and ACPA status at baseline may allow risk stratification for successful DMARD tapering and cost-effective use of biologic DMARD in patients in deep remission as defined by the 28-joint count Disease Activity Score using erythrocyte sedimentation rate.