Abstract BACKGROUND Inflammatory bowel disease (IBD) impacts multiple organ systems beyond the gastrointestinal tract. The presence of these extra-intestinal manifestations (EIMs) leads to significant morbidity for IBD patients and complicates treatment decisions. Advanced therapies (ATs) targeting intestinal inflammation alone may not be sufficient to effectively treat all EIMs. METHODS We conducted a descriptive retrospective cohort study using administrative claims data from the Optum® Market Clarity database (January 1, 2016–March 31, 2025). We identified IBD (ulcerative colitis, UC, or Crohn’s disease, CD) patients starting advanced therapies (biologics and small molecules) approved for IBD and calculated cumulative incidence (CI) and incidence rates (IR) per 1,000 person-years for newly developed classical EIMs in these patients. EIMs were identified individually (Figure 1) according to ECCO 2024 guidelines and further classified as bone/joint, skin, ocular, and hepatobiliary organ EIMs. RESULTS 22,442 IBD patients (12,496 with CD and 9,946 with UC) who initiated advanced therapies were followed for an average of 2.3 ± 2.03 years (UC) and 2.44 ± 2.06 years (CD). 47.9% were female, and the mean age was 49.3 years (SD = 18.3). Anti-TNFs (54.8% in UC and 60.4% in CD) were the most commonly initiated advanced therapy during the study period. The prevalence of classical EIMs was 21.5% in UC and 23% in CD. In both diseases, joint EIMs were the most common (UC, 13.1%; CD, 15%). 9.7% of UC and 11.0% of CD patients initiating advanced therapies subsequently developed at least one EIM during the follow-up period. Among patients who developed an EIM, the mean (SD) time from AT initiation to first EIM was 1.61 (1.63) years in UC and 1.61 (1.59) years in CD. Joint manifestations, followed by skin manifestations, were the most common incident EIMs in both diseases. The overall incidence of at least one EIM across drug classes was: anti-TNFs: 6.1% UC and 7.5% CD; anti-IL-12/23 or IL-23: 4.1% UC and 4.4% CD; anti-integrins: 5.9% UC and 8.1% CD; JAK-inhibitors: 3.8% UC and 2.5% CD. Amongst all drug classes, joint EIMs were the most frequent, followed by skin EIMs. CONCLUSION EIMs, especially those affecting joints and skin, remain a clinical challenge for patients with IBD. We demonstrate that many patients develop new EIMs within two years of initiating advanced therapies. The highest incidence of these EIMs was observed with anti-TNFs and anti-integrins. Further research is required.
Dubinsky et al. (Thu,) studied this question.