P5553 - Ustekinumab Induces Deep Remission in Refractory Ulcerative Colitis With Severe Extraintestinal Manifestations: A Comparative Immunotherapeutic Perspective

Hayder Alamily, MD¹, Sana Rabeeah, MD², Ban Mashadani, MD³, Bisher Sawaf, MD⁴, Mohannad Bitar, MD⁵, Mushfiqur Siddique, MD⁵, Sajjad Al-Badri, MBChB⁶, Abdulrahman Khaldoon. Hamid, MD⁷, Sandra Chehayeb, MD⁸, Mohamed Omar, MD⁸, Omer Najem, MD⁹
1University of Colorado Anschutz Medical Campus, Denver, CO; 2The University of Toledo, Toledo, OH; 3Baptist Health-University of Arkansas for Medical Sciences, North Little Rock, AR; 4University of Toledo Medical Center, Toledo, OH; 5Jamaica Hospital Medical Center, Jamaica, NY; 6College of Medicine, University of Baghdad, Baghdad, Baghdad, Iraq; 7Jamil Tutanji Hospital, Amman, 'Amman, Jordan; 8University of Kansas School of Medicine, Wichita, KS; 9Department of internal medicine, Trinity Health Oakland, Pontiac, MI

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 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.


Figure: Combined therapy response graphs

Disclosures:
Hayder Alamily indicated no relevant financial relationships.
Sana Rabeeah indicated no relevant financial relationships.
Ban Mashadani indicated no relevant financial relationships.
Bisher Sawaf indicated no relevant financial relationships.
Mohannad Bitar indicated no relevant financial relationships.
Mushfiqur Siddique indicated no relevant financial relationships.
Sajjad Al-Badri indicated no relevant financial relationships.
Abdulrahman Hamid indicated no relevant financial relationships.
Sandra Chehayeb indicated no relevant financial relationships.
Mohamed Omar indicated no relevant financial relationships.
Omer Najem indicated no relevant financial relationships.

Hayder Alamily, MD¹, Sana Rabeeah, MD², Ban Mashadani, MD³, Bisher Sawaf, MD⁴, Mohannad Bitar, MD⁵, Mushfiqur Siddique, MD⁵, Sajjad Al-Badri, MBChB⁶, Abdulrahman Khaldoon. Hamid, MD⁷, Sandra Chehayeb, MD⁸, Mohamed Omar, MD⁸, Omer Najem, MD⁹. P5553 - Ustekinumab Induces Deep Remission in Refractory Ulcerative Colitis With Severe Extraintestinal Manifestations: A Comparative Immunotherapeutic Perspective, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.