Extraintestinal Manifestations Remain Common After Advanced Therapy Initiation in IBD

Extraintestinal manifestations (EIMs) continue to affect a substantial proportion of patients with inflammatory bowel disease (IBD) even after initiation of advanced therapies, according to a large claims-based cohort study. The findings highlight the persistent systemic burden of IBD and the limitations of gut-focused treatment strategies in preventing nonintestinal complications.

Investigators conducted a retrospective analysis using the Optum® Market Clarity database, identifying more than 22,000 adults with ulcerative colitis (UC) or Crohn’s disease (CD) who initiated biologic or small-molecule therapies approved for IBD between 2016 and 2025. Patients were followed for a mean of approximately 2.4 years to assess the development of new classical EIMs, categorized according to European Crohn’s and Colitis Organisation (ECCO) guidelines.

At baseline, classical EIMs were already present in 21.5% of patients with UC and 23.0% of those with CD, with joint involvement being the most common. During follow-up, 9.7% of UC patients and 11.0% of CD patients developed at least one new EIM after starting advanced therapy. The average time to first EIM was just over 1.6 years in both diseases.

Joint manifestations accounted for the majority of incident EIMs, followed by skin involvement. Incidence varied by drug class. Anti–tumor necrosis factor therapies and anti-integrins were associated with the highest rates of new EIMs, whereas lower rates were observed with Janus kinase inhibitors and IL-12/23 or IL-23 inhibitors.

The authors concluded that “EIMs, especially those affecting joints and skin, remain a clinical challenge for patients with IBD,” and emphasized that “many patients develop new EIMs within two years of initiating advanced therapies.” They noted that the highest incidence occurred among patients treated with anti-TNFs and anti-integrins.

Control of intestinal inflammation does not reliably prevent systemic disease manifestations. These data reinforce the need for more comprehensive treatment approaches that address both intestinal and extraintestinal disease activity in IBD.

Reference
MC, Haris GA, Igho-Osagie E, et al. Incidence of extraintestinal manifestations in IBD patients treated with advanced therapies. Inflammatory Bowel Diseases. 2026; 32, Issue Supplement_1: izag006.052, https://doi.org/10.1093/ibd/izag006.052