P5534 - Dual-Targeted Therapy of Upadacitinib and Mirikizumab in Clinically Complex Ulcerative Colitis

Award: ACG Presidential Poster Award

Alex J. Mathew, MBE¹, Ushan A. Ranasinghe, MBBS², David T. Rubin, MD³
1University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL; 2University of Chicago, NorthShore Health Systems, Chicago, IL; 3University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA, Chicago, IL

Introduction: Upadacitinib and mirikizumab are each approved as monotherapy for patients with moderately-to-severely 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 (6-MP) 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 45mg/d and achieved a marked clinical response. However, maintenance dosing with 30mg/d in Sep 2023 led to symptom recurrence which was persistent despite escalation back to 45mg/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 (FCP) was 125 µg/g. She has since maintained clinical and endoscopic remission, confirmed by consistent low FCP 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 (IBD). 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 JAK inhibitors has been previously reported by our group and others, but not with mirikizumab. We demonstrate efficacy and safety of this unique approach.

Disclosures:
Alex Mathew indicated no relevant financial relationships.
Ushan Ranasinghe indicated no relevant financial relationships.
David Rubin: AbbVie – Advisory Committee/Board Member, Consultant, Speaker fees. Abivax SA – Consultant. Altrubio – Advisory Committee/Board Member, Consultant, Speaker feees, Stock Options. Avalo – Advisory Committee/Board Member, Consultant, Speaker fees. Bausch Health – Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Speaker fees. Buhlmann Diagnostics – Advisory Committee/Board Member, Consultant, Speaker fees. Celltrion – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. Cornerstones Health, Inc – Board of Directors membership. Douglas Pharmaceuticals – Consultant. Eli Lilly & Co. – Consultant. Foresee, Genentech (Roche) Inc. – Consultant. Image Analysis Group – Consultant. InDex Pharmaceutical – Consultant. Intouch Group – Advisory Committee/Board Member, Consultant, Speaker fees. Iterative Health – Advisory Committee/Board Member, Consultant, Speaker fees. Iterative Health – Stock Options. Janssen Pharmaceuticals – Consultant. Lilly – Advisory Committee/Board Member, Consultant, Speaker fees. Odyssey Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Speaker fees. Sanofi – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker fees. Throne – Consultant. Vedanta – Consultant.

Alex J. Mathew, MBE¹, Ushan A. Ranasinghe, MBBS², David T. Rubin, MD³. P5534 - Dual-Targeted Therapy of Upadacitinib and Mirikizumab in Clinically Complex Ulcerative Colitis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.