S5027 Ustekinumab Induces Deep Remission in Refractory Ulcerative Colitis With Severe Extraintestinal Manifestations: A Comparative Immunotherapeutic Perspective

Introduction: Ulcerative colitis (UC) can be complicated by extraintestinal manifestations (EIMs) in up to 40% of patients, significantly affecting quality of life and complicating treatment. While Tumor necrosis factor-α (TNF-α ) inhibitors are a cornerstone for moderate-to-severe UC, they may fail to achieve histologic remission or control systemic inflammation. Ustekinumab, an IL-12/23 inhibitor, has demonstrated potential in TNF-refractory cases, particularly when EIMs are prominent. This case illustrates the successful use of Ustekinumab in achieving complete remission in a patient with longstanding UC, systemic immune dysregulation, and intolerance to conventional immunomodulators. Case Description/Methods: A 39-year-old patient with scleroderma and UC (diagnosed 2012; pancolitis) was initially managed with mesalamine and rectal corticosteroids. Persistent inflammation led to azathioprine, discontinued due to hepatotoxicity. Adalimumab (started 2015) provided partial symptom relief but failed to induce histologic remission. By 2020, the patient developed debilitating EIMs—sacroiliitis, uveitis, and arthralgia—necessitating corticosteroids. Ustekinumab was initiated in 2021. Following standard induction and maintenance therapy, the patient achieved complete clinical, endoscopic, and histologic remission. EIMs fully resolved. The patient remains off corticosteroids and in sustained remission to date. Discussion: This case highlights the limitations of TNF-α inhibitors in managing refractory UC with systemic involvement. Despite partial luminal control, adalimumab failed to prevent or reverse EIMs. In contrast, Ustekinumab’s dual blockade of IL-12/23 modulates both mucosal and systemic inflammation, offering broader immunologic control. Comparative studies, including the SEAVUE trial in Crohn’s disease, demonstrate similar efficacy between Ustekinumab and adalimumab, with a superior safety profile for Ustekinumab. While direct UC trials are ongoing, real-world data supports its benefit in EIM resolution. This case reinforces the need for a treat-to-target strategy emphasizing histologic and systemic remission. Ustekinumab should be considered in complex UC cases where TNF-α therapy is inadequate or contraindicated.