P0997 Exclusive enteral nutrition induces early biochemical and transmural healing in adults with Crohn’s disease: Findings from the IMPLEMENT-CD study

Abstract Background Exclusive enteral nutrition (EEN) therapy is underused in adults with Crohn’s Disease (CD) reflecting concerns of tolerability and subsequent lack of efficacy. Traditional disease activity scores are unreliable and no longer sufficient as standalone markers of inflammation. Biochemical remission is now an accepted treatment target and transmural healing is an emerging marker of deep remission. Yet prospective EEN studies in adults evaluating these objective endpoints remain scarce . This study evaluated the efficacy of a 6-week EEN induction therapy using real-world clinical, biochemical and sonographic markers of disease activity. Methods This prospective, open labelled cohort study recruited adults (>18 years) with active CD (ACTRN12622000449730). Under dietetic supervision, patients received 6 weeks of polymeric EEN. Tapering corticosteroids and biological therapy were permitted. Eligibility was determined by presence of active disease, pragmatically defined as CD activity index (CDAI) ≥150, faecal calprotectin (FCP) >100µg/g, or bowel wall thickness (BWT) >3mm or increased Doppler on intestinal ultrasound (IUS). The composite outcome combined a clinical and objective marker of disease activity - clinical response or remission (CDAI reduction ≥100 or CDAI<150) plus either biochemical response or remission (FCP≥50% reduction or FCP<100µg/g ) or transmural response (≥25% BWT reduction) or healing, whichever was abnormal at baseline. Transmural healing required normal BWT, absent Doppler flow (modified Limberg=0), preserved wall stratification, and no inflammatory fat. Global sonographic inflammation was assessed by the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS). Results Fifty adults (mean age 42.3±16.3 years; 34 female) were recruited. Terminal ileal (25/50, 50%) and non-stricturing, non-penetrating disease (30/50, 60%) were most common (Table 1). Therapy was completed by 80% (40/50). The composite outcome was achieved by 38% (19/50). In those with clinically active disease, response and remission were 69% (25/36) and 21/36 (58%). Biochemical response and remission were 35% (12/34) and 12% (4/34). By IUS, transmural response and healing at week 6 was achieved in 48% (16/33) and 12% (4/33), respectively. In 51% (17/33), either transmural response or healing was observed . Mean IBUS-SAS fell from 65.4±27.1 to 48.7±31.2 (p = 0.001), and mean BWT reduced from 5.4±1.9 to 4.4±1.8 mm (p < 0.001)(Fig 1). Conclusion EEN is efficacious and induces early transmural response and healing within 6 weeks. This data supports EEN as a non-pharmacologic induction strategy in adults and highlights IUS as a non-invasive tool for disease monitoring. Further evaluation of the optimal duration of therapy is required. Conflict of interest: Dr. Chu, Matthew: None Bryant, Robert Venning: Robert V. Bryant has received grant/research support/speaker honoraria/advisory board fees from AbbVie, Ferring, Janssen, Shire, Takeda, GlaxoSmithKline, Bristol Myers Squibb, and Emerge Health and is a shareholder in Biomebank. Mathias, Ryan: Speakers fees from Pfizer, Johnson and Johnson (Janssen), travel grant support from Dr Falk Pharma, Abbvie, consulting fees GPEx Direen, Tennealle: No conflicts Broad, Lani: No conflicts Davis, Rachel: No conflicts Lynch, Kate: None Costello, Samuel: Employee: BiomeBank Shareholder: BiomeBank, Microbiotica Research funds and speakers fees: Janssen, Ferring, MSD, Microbiotica Edwards, Suzanne: No conflicts Day, Alice: Research Support from The Hospital Research Foundation and Michelle McGrath Fellowship, consultancy fees from Biome Bank, Ferring, AbbVie.