Real-world outcomes of ustekinumab, vedolizumab, and tumor necrosis factor inhibitors in very-early-onset inflammatory bowel disease: a multi-center cohort study

BACKGROUND: Very-early-onset inflammatory bowel disease (VEO-IBD), representing cases diagnosed before age 6 years, is increasing in prevalence. Although VEO-IBD often presents as severe, treatment-resistant disease requiring biologic agents, studies showing the effectiveness of biologics, such as ustekinumab (UST) and vedolizumab (VDZ), remain limited. METHODS: We retrospectively analyzed patients with VEO-IBD treated for at least a year from 13 institutions in Japan, evaluating clinical course including effectiveness of biologics, such as infliximab (IFX), adalimumab (ADL), UST, and VDZ. Patients with monogenic IBD were excluded. Steroid-free clinical remission (SFCR) and treatment persistence were assessed separately for first-line and for second-line or subsequent biologic therapies. RESULTS: We studied 101 VEO-IBD patients (56% male; median age, 3.6 years), including 40 with Crohn's disease, 52 with ulcerative colitis, and 9 with unclassified IBD. Biologics were used in 67 patients, most commonly infliximab (IFX; n = 52), followed by UST (n = 38), adalimumab (ADL; n = 23), and VDZ (n = 21). As first-line therapy, IFX and ADL achieved 1-year SFCR rates of 19% and 46%, with persistence rates of 36% and 48%. Despite being used mainly as second-line or subsequent therapies, UST and VDZ showed 1-year SFCR rates of about 45% and 36%, and maintained persistence of 79% and 46%, respectively, with UST demonstrating higher persistence than TNF-α inhibitors (P < 0.01). No discontinuations due to infusion reactions or other adverse events occurred with UST or VDZ. CONCLUSION: UST and VDZ were effective and well tolerated even when used as second-line or subsequent therapies for VEO-IBD.