Long-Term Feasibility, Adherence, and Exploratory Clinical Outcomes of Crohn’s Disease Exclusion Diet Plus Partial Enteral Nutrition in Adults with Crohn’s Disease

Background: Long-term data on the feasibility, adherence, and efficacy of the Crohn’s Disease Exclusion Diet combined with partial enteral nutrition (CDED + PEN) in adults with active Crohn’s disease (CD) remain limited. Methods: In this prospective, single-center cohort study, we assessed adherence, tolerability, clinical remission, nutritional and body composition changes in adults with clinically active CD following a 52-week 3-phase CDED + PEN protocol. Clinical activity, inflammatory markers, quality of life, nutritional intake, and body composition were evaluated at baseline and weeks 6, 12, and 52. Results: A total of 22 of 36 patients (61.1%, exact 95% CI:43.5–76.9%) remained adherent throughout the 52-week follow-up. Adherence overlapped with tolerability, as all discontinuations were attributable to poor tolerability. Adherence was higher in patients with disease duration ≤2 years (59.1% vs. 21.4%, p = 0.041) and in those with greater caloric (p = 0.012) and protein requirements (p = 0.022). All adherent patients achieved clinical remission after the 6-week induction phase, and remission was maintained at 12 months in 14/22 (63.6%). Harvey–Bradshaw Index scores decreased significantly at weeks 6 and 12, while fecal calprotectin decreased at week 6. Nutritional status improved, with sustained higher protein intake and early increases in total protein and albumin. Patients maintaining remission at 52 weeks showed greater reductions in C-reactive protein and fecal calprotectin, together with greater improvements in phase angle and muscle mass index. Conclusions: CDED + PEN is a feasible and safe long-term strategy for adults with active CD, particularly in early disease. It reduces disease activity, improves nutritional status and body composition, and supports durable remission in a substantial proportion of adherent patients.