OBJECTIVES: The aim of the study is to compare the cost per patient in sustained response/remission at 52 weeks follow-up across biologics (namely, vedolizumab, golimumab, adalimumab, and infliximab biosimilar) approved for the treatment of biologic naïve patients with moderate-to-severe ulcerative colitis (UC) from the Italian healthcare provider perspective. METHODS: The cost per biologic naïve patient with a sustained response or in sustained remission at 52 weeks follow-up was calculated by multiplying the number of patients needed-to-be-treated (NNT) for the respective outcome with the estimated healthcare provider´s incurred cost for administering each biologic — Patient with sustained response/remission being a patient with response/remission at the end of induction and maintenance among all patients starting induction. The efficacy data, namely the induction response probabilities and the NNTs, was derived from a systematic literature review of biologics randomized clinical trials and Bayesian meta-analysis. The current study considers both biologics acquisition costs and healthcare personnel resource costs to administer each biologic. The latter were estimated based on an activity-based costing study conducted in 3 Italian health facilities. RESULTS: The cost per patient in sustained response at 52 weeks for vedolizumab is estimated at €47,772 (95%CI €29,869; €101,055); and is the lowest compared to anti-TNF biologics. It is followed by infliximab biosimilar, golimumab 100mg at maintenance, golimumab 50mg at maintenance, and adalimumab; which achieved higher costs per patient in sustained response: €48,657 (95%CI €31,488; €95,523), €57,940 (95%CI €38,001; €106,206), €62,504 (95%CI €39,976; €120,477), €101,181 (95%CI €49,635; €422,334), respectively. Similarly, the cost per patient in sustained remission at 52 weeks for vedolizumab was the lowest across all biologics: €86,220 (95%CI €47,015; €206,652); followed by infliximab biosimilar: €92,562 (95%CI €52,954; €203,619). CONCLUSIONS: From an Italian healthcare provider perspective, vedolizumab may potentially be the most cost-effective treatment across biologics approved for the treatment of biologic naïve patients with moderate-to-severe UC.