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Background: Loss of response (LoR) to biologics in Crohn's disease (CD) is a significant clinical problem. Dietary therapy as a treatment strategy in this setting has not been previously reported. We report the use of dietary strategies using enteral nutrition coupled with the Crohn's Disease Exclusion Diet (CDED) for LoR.Methods: We have used dietary therapy as a salvage therapy for patients with biologic refractory disease or LoR. All cases of LoR to a biologic treated with dietary therapy as the sole salvage therapy in our unit. Patients with severe flares received 14 days of exclusive enteral nutrition followed by 6 weeks of CDED with Partial Enteral Nutrition (PEN) providing 50% of calories. Patients with non -severe disease received only CDED + PEN 50% for 12 weeks. Current and prior treatment, Harvey Bradshaw Index (HBI), CRP and albumin were recorded. All patients were seen at week 6 & 12 for follow up. Remission was defined as HBI <5 at week 6.Results: Twenty one patients, mean age 22.1±8.9 years. (11 adults and 10 children) met study criteria. Seventeen patients (81%) had used combination therapy, 10/21 (47.6%) were failing a second biologic. Dose escalation had failed in 13/21 (62%) patients. Clinical remission after 6 weeks was obtained in 13/21 (61.9%). Mean HBI decreased from 9.14±4.05 to 2.5±3.7 (p<0.001), mean CRP decreased from 3.2±3.4 to 1.1±2 (p=0.033) and mean albumin increased from 3.5±0.6 to 3.8±0.5 (p=0.06).Conclusions: Dietary therapy combining enteral therapy with the CDED may be a useful salvage therapy for patients failing biological therapy despite dose escalation.