Tailored step-up approach results in beneficial long-term disease outcome in the prospective Belgian Paediatric Crohn's disease registry (BELCRO)

L. WAUTERS (1), F. SMETS (2), E. DE GREEF (3), I. HOFFMAN (4), P. BONTEMS (5), S. VAN BIERVLIET (6), E. VAN DE VIJVER (7), I. PAQUOT (8), P. ALLIET (9), W. ARTS (10), B. HAUSER (11), H. PEETERS (12), M. DE VOS (13), P. BOSSUYT (14), J. RAHIER (15), O. DEWIT (16), O. DEWIT (16), T. MOREELS (16), F. FONTAINE (17), E. LOUIS (17), D. FRANCHIMONT (18), V. MULS (18), J. COCHE (19), F. BAERT (20), S. VERMEIRE (1), G. VEEREMAN (11) / [1] University Hospitals Leuven, Leuven, Belgium, Gastroenterology and Hepatology, [2] Clin universitaires St-Luc, UCL, Brussels, Belgium, Paediatric Gastroenterology, [3] UZ Brussel, Jette, Belgium, Paediatric Gastroenterology, [4] University Hospitals Leuven, Leuven, Belgium, Paediatric Gastroenterology, [5] HUDERF, City of Brussels, Belgium, Paediatric Gastroenterology, [6] UZ Gent, Gent, Belgium, Paediatric Gastroenterology, [7] UZ Antwerpen, Antwerp, Belgium, , Belgium, Pediatric Gastroenterology, [8] CHC Clinique de l'Esperance, Liège, Belgium, Paediatric Gastroenterology, [9] Jessa Hospital, Hasselt, Belgium, Paediatric Gastroenterology, [10] ZOL, Genk, Belgium, Paediatric Gastroenterology, [11] UZ Brussel, Jette, Belgium, Pediatric Gastroenterology, [12] AZ St Lucas, Ghent, Belgium, Gastroenterology, [13] UZ Gent, Gent, Belgium, Gastroenterology, [14] Imelda Hospital, Bonheiden, Belgium, Gastroenterology, [15] UCL, Mont-Godinne, Belgium, Gastroenterology, [16] Clin universitaires St-Luc, UCL, Brussels, Belgium, Gastroenterology, [17] CHU Liege, Liège, Belgium, Gastroenterology, [18] ULB Hôpital Erasme, Brussels, Belgium, Gastroenterology, [19] Clinique St. Pierre, Ottignies, Belgium, Gastroenterology, [20] Heilig Hart Ziekenhuis, Roeselare, Belgium, Gastroenterology Introduction The prolonged use of biologic agents with or without immunomodulators (IM) remains controversial in the management of paediatric Crohn’s disease (CD). Aim The prolonged use of biologic agents with or without immunomodulators (IM) remains controversial in the management of paediatric Crohn’s disease (CD). Methods Five-year follow-up (FU) data from the BELCRO, an observational prospective cohort of children (< 18 years) diagnosed with CD in Belgium, were analysed. Disease severity was scored as inactive, mild or moderate-to-severe on a 3-point PCDAI scale and monitored yearly. Treatment and outcomes were recorded from diagnosis until 5 yrs FU. Remission was defined as inactive disease and sustained remission when achieved for ≥ 2 yrs FU. Univariate analyses were performed between patients with or without anti-TNF and Spearman’s correlation between treatment and outcomes. Results A total of 91 patients (median (IQR) age 12.7 (10.9 – 14.8) yrs, 53% male) were included. Disease location was 12% ileal, 23% colonic (L2), 64% ileocolonic, 76% upper GI and 30% perianal. Disease severity was 25% mild and 75% moderate-to-severe. Anti-TNF was started in 73% after median (IQR) 1.1 (0.6 – 2.2) yrs with duration of 3.9 (2.5 – 4.7) yrs of which 89% combination therapy with duration of 1.3 (0.6 – 2.0) yrs. Older age (13.1 (11.5 – 15.2) vs. 11.8 (8.7 – 13.8) yrs; p< .05) and location L2 (29% vs. 8%; p= .04) were associated with need to start anti-TNF. Despite shorter delay to corticosteroids (CS) (0 (0 – 0.02) vs. 0.02 (0 – 0.06); p= .04), total duration of CS was similar and total duration of IM (2.5 (1.4 – 4.7) vs. 4.7 (3.6 – 5.2); p= .001) was shorter in the anti-TNF group. Time to first (1.1 (0.5 – 1.8) vs. 0.6 (0.3 – 1.1); p= .01) and sustained (2.9 (2.3 – 3.9) vs. 2.3 (2.1 – 2.9); p= .03) remission was longer with anti-TNF use. Mean disease severity (1.7 (1.4- 1.9) vs. 1.4 (1.3- 1.6); p< .01) during 5 yrs FU was higher with anti-TNF but rates of inactive disease (65% vs. 76%; p= .32) after 5 yrs FU were similar with less ongoing CS (41% vs. 72%; p= .008) in the anti-TNF group. Delay to IM treatment was correlated with mean disease severity (r= .26; p= .02) and duration of CS with duration of sustained remission (r= -.24, p= .03), though not significantly after correction for multiple testing. Rates of perianal flares, hospitalizations or surgery were similar and no serious opportunistic infections, cancer or deaths were reported with use of anti-TNF. Conclusions Prospective data from the BELCRO demonstrate beneficial long-term outcomes using a step-up approach with anti-TNF in over 2/3 of patients, limiting IM treatment. The gain of top-down and early combination therapy remains to be determined in paediatric CD.