INTRODUCTION: Mirikizumab, approved for the treatment of moderately to severely active ulcerative colitis (UC), may be prescribed in a similar placement to ustekinumab in second-line settings. Payers may compare the economic value when making formulary decisions. This study estimated and compared the cost per remission of the second-line therapies mirikizumab versus ustekinumab in patients with UC. METHODS: An Excel-based analytic model was developed to estimate the cost per additional patient achieving clinical remission at the end of one year in biologic/Janus kinase inhibitor (JAKi)-experienced patients (second-line therapy) with UC from a United States commercial payer perspective. A network meta-analysis of published pivotal randomized clinical trials was used to derive the number needed to treat (NNT) for clinical response, clinical remission, and endoscopic remission/endoscopic improvement/mucosal healing for ustekinumab and mirikizumab in the study population. The model included the treatment cost (wholesale acquisition costs [WAC] and treatment administration costs) during the induction and maintenance phases. A scenario involving the availability of a ustekinumab biosimilar was also evaluated, assuming the NNT remained the same as ustekinumab but with a WAC set at 50% lower than its current WAC. RESULTS: The costs per patient achieving clinical remission for mirikizumab vs. ustekinumab as a second-line therapy were $461,096 vs. $67,273 during induction and $501,456 vs. $1,079,189 during maintenance. The cost per clinical remission in case of dose escalation during maintenance was lower for mirikizumab vs. ustekinumab ($501,456 vs. $1,569,127). Considering the ustekinumab 130 mg IV biosimilar, the scenario resulted in a lower cost per clinical remission for mirikizumab vs. a ustekinumab biosimilar during the maintenance phase ($501,456 vs. $539,594). CONCLUSION: Mirikizumab is projected to have a lower cost per remission during maintenance therapy than ustekinumab. Given the need for long-term treatment for this chronic condition, mirikizumab appears to be a cost-efficient treatment option.