OBJECTIVES: European registries of Rheumatoid Arthritis (RA) patients treated by biological agents suggest that 70-80% are maintained in first line at 1 year despite potential insufficient efficacy. Post hoc analyses of certolizumab pegol (CZP) studies indicate that a 3 month clinical response had a high predictive value of the 1 year outcome. The objective was to examine the efficiency of a strategy consisting of early switching from CZP to a second line TNF inhibitor in case of insufficient clinical response at 3 months (3M) in the French setting versus current clinical practices. METHODS: A decision-tree model was built to estimate the clinical outcomes (ACR50 cumulated time) and the direct costs of different cohorts of RA patients over a 2 year period. ACR50 was considered as an RA satisfying clinical outcome. The “3M tight control” strategy consisted of stopping CZP at 3 months in patients not achieving the ACR50 criterion and switching them to other biologics. Three reference cohorts treated with first line CZP, etanercept or adalimumab, respectively, according to current clinical practices were considered as comparators (reference). All TNF inhibitors were assumed to have equal efficacy in first line. Costs were estimated at 2013 French public prices. RESULTS: The proportion of patients achieving ACR50 after a 2 year follow-up was 58% in all reference cohorts and 75% in the “3M tight control” CZP strategy cohort. The costs per patient-year in ACR50 were €19,326 with the “3M tight control” strategy cohort and €23,588, €26,774 and €30,285 for the CZP, etanercept and adalimumab reference cohorts, respectively. The strategy “3M tight control” had an incremental cost-effectiveness ratio of €5,605/patient-year in ACR50 versus CZP reference, and was dominant versus etanercept or adalimumab reference. CONCLUSIONS: A 3-month tight control management of RA patients with CZP as first line treatment is cost-effective compared to alternatives.