P0548Symptom assessment of IBD-related quality of life after ustekinumab treatment in paediatric crohn’s disease

Abstract Background The IMPACT-III is the most commonly used disease-specific health-related quality of life (HRQoL) metric used in paediatric clinical trials. We assessed the effect of ustekinumab treatment on disease-specific symptoms of the IMPACT-III (symptom facets of the “Well-being” domain), to capture symptoms closely related to underlying Crohn’s disease (CD) pathophysiology and assess the potential for improved responsiveness to change. Methods UNITI Jr is a phase 3, multicenter interventional study of ustekinumab in paediatric participants (ages 2 to 18 years) with moderately to severely active CD. There was an 8-week open-label induction period (N = 101) with a single dose of intravenous ustekinumab followed by a randomized double-blind, 2-arm maintenance period (N = 97) with subcutaneous ustekinumab given every 8 (Q8W) or 12 weeks (Q12W), each for 44 weeks, totaling 52 weeks. Disease-specific HRQoL was assessed with the IMPACT-III questionnaire, administered to participants ≥10 years old at Week (W)0 and W52. Symptoms were assessed with the original 6-domain and a modified 4-domain IMPACT-III where the “Well-being” subdomain reflects only bowel and systemic symptoms (previously reported).1 To minimize overlapping content with the Paediatric Crohn’s Disease Activity Index (PCDAI), we also removed the abdominal pain item from “Well-being” subdomain (Figure). Mean change from baseline (CFB) to W52 (transformed scores) is reported. Clinical meaningfulness was assessed with distribution-based methods (0.5 standard deviation SD threshold). Results In the full analysis set (n = 77), mean (SD) baseline IMPACT-III total score was 101.7 (23.89). At W52, mean CFB (SD) of the 6-domain IMPACT-III transformed total score was 13.7 (19.99). The most responsive subdomain scores were (mean CFB SD): “Bowel symptoms” (20.2 26.91) and “Systemic symptoms” (19.3 27.80).1 Mean CFB (SD) for the modified 4-domain Impact-III, Well-being Subdomain “symptom facets” was 21.7 (28.32). CFB (improvement) exceeded the 0.5 SD threshold. Conclusion In paediatric participants with moderately to severely active CD, ustekinumab yielded distribution-based clinically meaningful improvements in disease-specific HRQoL symptoms relevant to paediatric IBD patients. Removing overlapping items with the PCDAI symptoms from the modified 4-domain IMPACT-III symptom scale strengthened its responsiveness and fit-for-purpose status as an endpoint, supporting the primary outcome measure by demonstrating “additional treatment effects” beyond PCDAI-driven changes. Reference: 1. Fieo R, et al. Assessment of IBD-Specific Quality of Life (IMPACT-III) Symptoms After Treatment With Ustekinumab in Pediatric Crohn’s Disease. Poster presented at Paediatric IBD Porto Group (PIBD) 2025 meeting:7th International Symposium on Paediatric Inflammatory Bowel Disease; October 22-25, 2025; Sorrento, Italy Conflict of interest: Prof. Dr. Griffiths, Anne: Grant: Abbvie Personal Fees: Abbvie, Alfasigma, Amgen, Janssen, Lilly, Merck, Pfizer, Roche, Takeda received medical writing assistance for this abstract from Johnson and Johnson AMG received medical writing assistance for this abstract from Johnson and Johnson Fieo, Robert: Employee of Janssen Pharmaceuticals/Johnson & Johnson received medical writing support from Johnson & Johnson Volger, Sheri: employed by Johnson & Johnson Innovative medicine and have stock in the company received medical writing support from Johnson & Johnson Strauss, Richard: Employee of Johnson & Johnson and may hold stock or stock options in Johnson & Johnson. received medical writing support from Johnson & Johnson Kim, Lilianne: I’m an employee of Johnson and Johnson Innovative Medicine and I hold stocks in the company received medical writing support from Johnson & Johnson