OP15 Cyclic exclusive enteral nutrition to maintain longterm drug-free remission in Paediatric Crohn’s Disease: The CD HOPE study of the GETAID pédiatrique

Abstract

Objectives and Study: Nutritional therapy is recommended as first choice induction therapy for luminal active Crohn's disease (CD). To address the question if patients responding to nutritional induction therapy can be maintained in remission on dietary therapy without the use of immunosuppressive drugs, we designed a prospective randomized trial (CD-HOPE) comparing cyclic exclusive enteral nutrition to daily supplement over a 12 month period. Methods: New onset patients (6-17 years) with a confirmed diagnosis of CD (or CD patients experiencing a relapse) who successfully completed a cycle of at least six weeks of EEN with clinical remission (wPCDAI ≤12.5) were recruited in n= 21 investigational sites of the French paediatric IBDnetwork GETAID pédiatrique between 12.2014 and 09.2018. All drug therapy had to be stopped at least 4 weeks prior to inclusion. A total of n=112 patients were screened with n=100 patients randomized successfully to group A cyclic EEN (100% of caloric requirement) every 8 weeks for 2 weeks or group B daily supplementary nutrition (25% of caloric requirement). Patients were stratified according to age (< 10 years or older) and previous drug exposure or not. EEN and the nutritional supplement were in form of MODULEN IBD ®. Except for the two weeks of EEN in group A food access was not restricted. Primary objective of CD HOPE was the comparison of relapse rates at 12 months (defined as a wPCDAI >12.5 at two consecutive visits) between the two groups (log-rank test per protocol). The additional analyses were performed using a multivariate regression analysis and cox model. Results: N=49 CD patients were successfully randomized to group A (cyclic EEN) and 51 to group B (daily supplement) with 43/49 and 44/51 newly diagnosed patients without any previous drug exposure (group A and B, respectively). The baseline characteristics were comparable between the two groups. Median age was 12 and 13 years, group A and B respectively. At the final 12 months visits a total of 25/49 patients (group A) remained in remission without disease activation compared to 12/51 patients (group B) (p=0.004) with a hazard ratio of 0.48 (0.29-0.80) (p= 0.0051). Kaplan Maier survival remission rates are shown in figure 1. Mean fecal calprotectine levels were not significantly different between the two groups (297, 399 and 469 at month 0, 3, and 12 visits in group A and 480, 606, and 283 at month 0,3, and 12 visits in group B). Mucosal healing was evaluated at 12 months of therapy in 25/49 patients (group A) and 18/51 patients (group B), with a mucosal healing rate of 52% (group A) and 33% (group B). Both treatment arms showed a significant catch-up growth. Conclusions: This is the first randomized trial indicating that children/adolescents with CD responding to EEN as induction therapy can be maintained on longterm remission with a nutritional therapy without use of immunosuppressive drugs/biologics. While daily nutritional supplement with normal access to food was not successful with a relapse rate of 76%, cyclic EEN over 2 weeks every 8 weeks allowed to maintain half of the patients in remission with mucosal healing.