S5008 Dual-Targeted Therapy of Upadacitinib and Mirikizumab in Clinically Complex Ulcerative Colitis

Introduction: Upadacitinib and mirikizumab are each approved as monotherapy for patients with moderately-to-severely ulcerative colitis (UC); however, their combined efficacy and safety have not been previously reported. We present a case of medically resistant ulcerative colitis successfully treated with the combination of upadacitinib and mirikizumab. Case Description/Methods: A 40-year-old woman with a history of left-sided UC diagnosed in 2003 initially achieved clinical remission with mesalamine and then switched to balsalazide. Despite this maintenance therapy, she experienced multiple disease relapses. In 2006, she was treated with both mesalamine and 6-mercaptopurine and achieved clinical remission which was sustained for 12 years. After a relapse in Feb 2018, she switched to vedolizumab and achieved deep remission. A subsequent relapse in Aug 2022 prompted a switch to infliximab and reintroduction of mesalamine, however, this was not effective. In June 2023, she initiated induction therapy with upadacitinib 45 mg/d and achieved a marked clinical response. However, maintenance dosing with 30 mg/d in Sep 2023 led to symptom recurrence which was persistent despite escalation back to 45 mg/d. In Jan 2024 mirikizumab was added to the upadacitinib which was dropped to 15 mg/d; mesalamine was continued. The patient achieved clinical remission shortly thereafter, and her fecal calprotectin was 125 µg/g. She has since maintained clinical and endoscopic remission, confirmed by consistent low fecal calprotectin levels in subsequent tests and endoscopic findings demonstrating deep remission in Sep 2024. Discussion: Dual-targeted therapy, combining agents that target distinct inflammatory pathways, is an emerging approach in refractory inflammatory bowel disease. We present the first case of a patient with relapsing and medically resistant UC who achieved sustained clinical and endoscopic remission with combined mirikizumab and low dose upadacitinib. Combination IL23 inhibitor and Janus Kinase inhibitors has been previously reported by our group and others, but not with mirikizumab. We demonstrate efficacy and safety of this unique approach.