P864 The Effect of Ustekinumab on Mucosal Inflammation in Paediatric Crohn’s Disease: The REALITI Real-World Evidence Effectiveness Study

Abstract

Abstract Background Crohn's disease (CD) research using real world evidence (RWE) has been hampered by lack of validated endoscopic outcome measures. The recently validated Simplified Endoscopic Mucosal Assessment of CD (SEMA-CD) provides a reliable way to evaluate mucosal inflammation in paediatric CD patients (pts), making it suitable for use in clinical practice and relevant to real world data. REALITI is a RWE study of the effectiveness and safety of ustekinumab (UST) in paediatric pts. Methods REALITI used data from pts with CD in the ImproveCareNow (ICN) registry. Colonoscopy reports (reports) from 2010-2020 identified by chart review were redacted and uploaded to the registry. Central endoscopy readers underwent SEMA-CD training and were randomly assigned to score reports. No reader reviewed reports from their own institution. Three readers independently scored reports blinded to each other’s scores and to clinical information. Demographic and clinical data, prospectively recorded in ICN, were summarized and compared between pts with and without endoscopy. Clinical remission was defined as Short Paediatric CD Activity Index (sPCDAI) ≤10 and endoscopic remission as SEMA-CD ≤1. Results Analyses of mucosal inflammation by SEMA-CD in 114 pts age 2 to <18 yr with moderate-severe CD (sPCDAI ≥30) and body weight ≥40 kg at UST initiation (baseline) and after 52 weeks (wk) of treatment are reported. Overall, 77/114 pt had ≥1 report during the study and 20 had a report at Wk 52. Baseline median age of all pts was 16 yr (interquartile range [IQR] 15-16). Pts with endoscopic assessments (N=77) vs pts without (N=37) were more often female (56% vs 41%) and had more ileocolonic disease activity (73% vs 54%), perianal disease (39% vs 35%), and stricturing phenotype (B2; 10% vs 5%), respectively. No pts had B2/B3 phenotype. At baseline, median sPCDAI for all pts was 40 (IQR 35-50; N=114) and median SEMA-CD was 8.5 (IQR 5-13; N=38). At Wk 52, 4/20 pts (20% [95% CI, 8.1%, 41.6%]) were in endoscopic remission. Despite small sample sizes, there appears to be lower clinical remission rates at Wk 52 in pts with baseline endoscopic assessments (17/77; 22.1% [95% CI, 14.3%, 32.5%]) vs without (10/37; 27.0% [95% CI, 15.4%, 43,0%). Conclusion Use of SEMA-CD to assess mucosal inflammation in paediatric pts with moderate-severe CD treated with UST demonstrated rates of endoscopic remission similar to clinical remission at Wk 52. Endoscopy was performed more often in sicker pts, with a greater proportion of pts who did not undergo endoscopy achieving clinical remission. Future routine SEMA-CD assessment of mucosal inflammation in clinical practice may improve analyses in observational and retrospective studies.