Surgical treatment DOP037 A model for prediction of ...

Abstracts of the 12th Congress of ECCO – European Crohn’s and Colitis Organisation of cells homozygous for high affinity FcgRIIIa158V compared to low affinity FcγRIIIa158F. Interestingly, hypo-fucosylation of the antibody Fc region enhances binding affinity specifically for FcgRIIIa. Indeed, hypo-fucosylation of anti-TNF increased the amount of CD206+ macrophages in vitro, especially for cells expressing low affinity FcgRIIIa158F. Finally, hypo-fucosylated anti-TNF increased the generation of CD206+ macrophages in the colon and displayed significantly improved therapeutic efficacy in vivo. Conclusions: FcgR engagement by anti-TNF is required for the therapeutic efficacy in IBD. Increasing the Fc binding affinity of anti-TNF with hypo-fucosylation significantly improved therapeutic outcome. Anti-TNF therapy currently achieves mucosal healing in less than 50% of patients, antibody glycoengineering could be an effective future strategy and might be of special interest for patients carrying the low affinity FcgRIIIa158F allotype.

DOP Session 5: Surgical treatment

DOP037 A model for prediction of early surgery and complications in paediatric Crohn’s disease: results of the prospective GROWTH CD study A. Levine*1,2 , S. Hussey3 , K.L. Kolho4 , M. Sladek5 , J.M. de Carpi6 , D. Turner7 , R.K. Russell8 , N. Cohen-Dolev9 , J. Escher10 , Porto-ECCO GROWTH CD Study Group 1 Edith Wolfson Medical Center, Department of Paediatric Gastroenterology and Nutrition Unit, Holon, Israel; 2 Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel; 3 National Children’s Research Centre, UCD and RCSI, Dublin, Ireland; 4 Children’s Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland; 5 Jagiellonian University Medical College, Krakow, Poland; 6 Hospital Sant Joan de Deu, Department of Paediatric Gastroenterology, Barcelona, Spain; 7 Shaare Zedek Medical Center, Department of Paediatric Gastroenterology, Jerusalem, Israel; 8 The Royal Hospital for Children, Department of Paediatric Gastroenterology, Glasgow, United Kingdom; 9 Edith Wolfson Medical Center, PIBD Research Center, Department of Paediatric Gastroenterology and Nutrition Unit, Holon, Israel; 10 Children’s Hospital Erasmus MC Sophia, Department of Paediatric Gastroenterology, Rotterdam, Netherlands Background: Children with Crohn’s disease (CD) are at a high risk for complications from both disease and treatment. The ability to predict risk and adverse outcomes at or close to diagnosis would allow patients to be stratified by risk, in order to avoid under treatment or overtreatment while reducing adverse outcomes from drug and disease. The goal of the current prospective study was to identify factors that would predict early complicated disease behavior or surgery. Methods: The GROWTH CD study (Growth, Relapses and Outcomes With THerapy) is geared to identify factors that could predict early outcomes such as complications (stricturing, penetrating or perianal abscess)and surgery by 24 months. Newly diagnosed children underwent colonoscopy, gastroscopy and imaging. They were phenotyped by the Paris classification and followed at baseline, 8, 12, 26, 52, 78 and 104 weeks. Twenty dichotomous and continuous variables were assessed, including serum biomarkers (ASCA, CBIR1, OMPC), measures of inflammation (ESR, CRP, Calprotectin), disease activity (PCDAI and PGA) and serum albumin. Predictors at

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diagnosis and week 12 (post induction treatment) served as prediction time points. Complications and surgery were recorded at weeks 78 and 104. Logistic regression and risk modeling was performed for best fit models. Results: 285 children, median age 13 yrs, 60% male, were followed prospectively for 2 years, of whom 78 (27.3%) developed complications and 28 (9.8%) required surgery. Use of immunomodulators by 12 weeks was not associated with decreased risk, (complications and surgery both p=0.9). Presence of a complication at diagnosis and PCDAI>30 at week 12 (OR 4.2, CI 1.16–16.77) p=0.03, were predictive of complications. Five parameters predicted increased risk of surgery (high ESR>50 wk 0, stricturing disease at diagnosis, ASCA, hypoalbuminemia or elevated PCDAI >10 at week 12). The first 4 remained in the best fit model. The combination of Paris B2 (OR 4.2, CI 1.3–12.7) p=0.01, ESR>50 (OR 2.9, CI1.004–8.642) p=0.049 at baseline, and Alb