947 TOP-DOWN INFLIXIMAB SUPERIOR TO STEP-UP IN CHILDREN WITH MODERATE-TO-SEVERE CROHN'S DISEASE - A MULTICENTER RANDOMIZED TRIAL Maria Jongsma, Martine Aardoom, Maarten Cozijnsen, Merel van Pieterson, Tim de Meij, Obbe F. Norbruis, Michael Groeneweg, Victorien Wolters, Herbert M. van Wering, Iva Hojsak, Kaija-Leena Kolho, Thalia Hummel, Janneke Stapelbroek, Patrick van Rheenen, Michiel P. van Wijk, Sarah Teklenburg-roord, Johanna C. Escher, Janneke N. Samsom, Lissy de Ridder Background: In newly diagnosed pediatric Crohn’s Disease (CD) patients current guidelines instruct to start exclusive enteral nutrition (EEN) or oral prednisolone in combination with immunomodulators to achieve remission. Infliximab (IFX) is proven to be highly effective in pediatric CD patients, but mostly used once patients are refractory, the so called step- up (SU) treatment strategy. However, evidence is emerging IFX is more effective the sooner it is initiated. We investigated whether initiation of IFX directly after diagnosis in moderate- to-severe CD, i.e. top-down (TD) treatment, results in a higher long-term remission rate than SU treatment. Methods: For this international randomized controlled trial (RCT) patients aged 3-17 years, with new-onset, untreated CD with weighted pediatric CD activity index (wPCDAI) >40 were included. TD treatment consisted of 5 IFX (CT-P13) infusions of 5 mg/kg (0, 2, 6, 14, 22 weeks) combined with azathioprine (AZA). After 5 infusions, IFX was stopped while continuing AZA. SU treatment consisted of induction therapy with EEN or oral prednisolone combined with AZA as maintenance treatment. In both groups, IFX could be (re)started on predefined conditions. Primary endpoint of this study was sustained clinical remission (wPCDAI <12.5) at week 52 without need for additional therapy or surgery. Secondary endpoints included IFX use at week 52, mucosal healing (SES-CD <3) and low fecal calprotectin levels (<250 ug/g) at week 10. Results: 100 patients were included in 12 centers. Three out of 100 patients did not start with the study after randomiza- tion (n=97; 49 TD vs 48 SU). At week 52, 19/46 (41%) of TD patients were in clinical remission without a need for treatment intensification or surgery, while in the SU group this number was significantly lower (7/48, p=0.004). After induction therapy, IFX was (re)started in 18/49 (36%) TD patients compared to 29/48 (60%) SU patients within 52 weeks (p=0.02). Three patients underwent surgical resection (ileocecal resection), one TD patient and two SU treated patients. At week 10, significantly more TD (27/44, 61%) than SU treated patients (17/44, 39%) were in clinical remission (p=0.033). 57/97 consented to endoscopy at week 10. Endoscopic remission rates were higher in TD (16/27 [59%], median SES-CD 1 [IQR 0-5]) than SU treated patients (5/30 [17%], median SES-CD 6 [IQR 3-16], p=0.001). Similarly, low fecal calprotectin levels were more frequent in the TD group (n= 75; TD 21/40 [53%] vs SU 9/35 [26%], p=0.027). Conclusion: We are the first to compare TD IFX to SU treatment in an RCT of paediatric CD patients. TD treatment was superior to SU in achieving sustained clinical remission. Therefore, we advise to start IFX directly after diagnosis in moderate-to-severe paediatric Crohn’s disease patients. 948 A NOVEL SUBCUTANEOUS INFLIXIMAB (CT-P13) IN PATIENTS WITH ACTIVE CROHN’S DISEASE AND ULCERATIVE COLITIS: WEEK54 AND SWITCHING RESULTS FROM A MULTICENTER, RANDOMISED CONTROLLED PIVOTAL TRIAL Walter Reinisch, Jaroslaw Leszczyszyn, Robert Dudkowiak, Adi Lahat, Beata Gawdis- Wojnarska, Aldis Pukitis, Marek Horynski, Katalin Farkas, Jaroslaw Kierkus, Maciej Kowalski, Stefan Schreiber, Shomron Ben-Horin, Sang Joon Lee, Sung Hyun Kim, Han Na Kim, Mi Rim Kim, Yun Ah Kim, Byong Duk Ye BACKGROUND: Two randomized controlled trials of a novel subcutaneous (SC) formulation of infliximab in patients with active rheumatoid arthritis 1 and in patients with active Crohn’s disease (CD) and ulcerative colitis (UC) 2 confirmed comparable clinical efficacy and safety of CT-P13 SC with CT-P13 intravenous (IV) up to Week 30. We now present the efficacy, pharmacokinetics (PK) and safety of CT-P13 SC over 1-year in the active CD and UC trial, including the outcome in patients switched from CT-P13 IV to CT-P13 SC. METHODS: After loading doses of IV 5 mg/kg at Weeks 0 and 2, patients were randomized at Week 6 to receive either SC 120 mg (<80 kg) or 240 mg ( ≥80 kg) every 2 weeks (SC arm), or to continue IV 5 mg/kg every 8 weeks (IV arm). From Week 30, IV 5 mg/kg was switched to either SC 120 or 240 mg based on the patients’ body weight at Week 30. Patients who initially responded but experienced loss-of-response at Week 30 or beyond, were dose- escalated to SC 240 mg every 2 weeks. RESULTS: A total of 131 patients were randomized (66 to the SC arm and 65 to the IV arm), of whom 105 (80.2%) patients completed the Week 54 visit (55 in the SC arm and 50 in the IV arm). The CDAI and partial Mayo scores showed comparable improvement in the 2 arms at Week 30 and also at Week 54 after switching the remaining IV patients to SC (Table 1). The rates of clinical response and remission were also maintained at Week 54 (Table 1). The proportion of combined CD and UC patients achieving mucosal healing (SES-CD score ≤2 for CD and Mayo endoscopic subscore ≤1 for UC) was comparable at Week 54 (66.7% [32/48 patients] in the SC arm and 69.8% [30/43 patients] in the IV arm). The mean pre-dose serum concentrations in the IV arm increased to a similar level to SC arm after switching and was maintained until Week 54 (Figure 1). The safety profiles during the maintenance phase and after Week 30 were generally comparable between the 2 arms (Table 1). All of localized injection site reactions were grade 1 or 2 in intensity. CONCLUSION: These results of CT-P13 SC 1- year study in active CD and UC show comparable efficacy and safety of the SC and IV formulations, which was similar whether the patients started SC dosing directly after IV induction or after 6 months of IV dosing. The PK as manifested by trough concentrations of the drug, increased after switching to SC from 6 months of IV dosing. These observations support the first infliximab SC formulation is a viable therapeutic agent whether used early after induction or whether patients switch from IV to SC during maintenance. REFERENCES: 1. Westhovens R. et al., SAT0170, European League Against Rheumatism, 2019. 2. Schreiber S. et al., LB02, United European Gastroenterology Week, 2019. S-193 AGA Abstracts 949 EFFICACY AND SAFETY OF 2 VEDOLIZUMAB IV REGIMENS IN PATIENTS WITH PERIANAL FISTULIZING CROHN'S DISEASE: RESULTS OF THE ENTERPRISE STUDY David A. Schwartz, Laurent Peyrin-Biroulet, Karen Lasch, Shashi Adsul, Silvio Danese Background: Perianal fistulae occurring with Crohn’s disease (CD) are a challenge to treat. Vedolizumab (VDZ) is a gut-selective, monoclonal α 4 β 7 integrin antibody approved to treat patients with moderately to severely active CD. Here we report results from ENTERPRISE (NCT02630966; EudraCT 2015-000852-12), a randomized, double-blind, phase 4 trial to evaluate 2 VDZ IV dosing regimens in patients with fistulizing CD. Methods: Patients with moderately to severely active CD and 1-3 draining perianal fistulae received either VDZ 300 mg IV at Weeks (Wk) 0, 2, 6, 14, and 22 (VDZ), or the same regimen plus an additional VDZ dose at Wk10 (VDZ+Wk10). The primary endpoint was the proportion of patients with a ≥50% reduction from baseline in number of draining fistulae (absence of draining despite gentle finger compression) at Wk30. Secondary endpoints were the proportion of patients with a ≥50% reduction from baseline in number of draining fistulae at Wk22 and Wk30, and the proportion of patients with 100% fistulae closure at Wk30. Patients with missing data at study visits were counted as non-responders. Perianal disease activity index (PDAI), perianal pain score, Van Assche score, gadolinium contrast enhancement by pelvic MRI, and safety were assessed. Study enrollment closed early due to slow recruitment; thus, all analyses are descriptive. Results: Of the 32 patients with post-baseline assessment of fistulae healing (full analysis set), 28 had ≥1 draining fistula at baseline (modified full analysis set). Median CD duration was 8.5 y (VDZ [n=14]: 11.2 y; VDZ+Wk10 [n=14]: 6.1 y). In each arm, 11 patients (78.6%) had prior anti-tumour necrosis factor therapy at baseline; concomitant corticosteroid use was 21.4% (VDZ) and 14.3% (VDZ+Wk10), and concomitant immunosuppressant use was 28.6% (VDZ) and 21.4% (VDZ+Wk10). At Wk30, 53.6% of all patients achieved ≥50% decrease in number of draining fistulae (VDZ: 64.3%; VDZ+Wk10: 42.9%; Figure 1); improvement was rapid with 42.9% of patients responding at Wk2 (VDZ: 50.0%; VDZ+Wk10: 35.7%). A decrease of ≥50% in number of draining fistulae at both Wk22 and Wk30 was achieved by 46.4% of patients (VDZ: 57.1%; VDZ+Wk10: 35.7%). Closure of all fistulae draining at baseline was observed at Wk30 in 42.9% of patients (VDZ: 50.0%; VDZ+Wk10: 35.7%). In the full analysis set, mean (SD) PDAI scores changed from baseline to Wk30 –4.1 (3.3) and perianal pain scores changed –2.2 (2.7) ( Table 1). At Wk30, mean (SD) Van Assche scores and contrast enhancement scores changed –1.1 (3.1) and –9.5 (69.4) from screening, respectively. No new safety signals were observed. Conclu- sions: Over half of CD patients treated with VDZ had reductions of ≥50% in the number of draining perianal fistulae. Clinically relevant reductions in draining fistulae were seen as early as Wk2 and maintained through Wk30. AGA Abstracts