Introduction

Exclusive enteral nutrition (EEN) is effective for inducing remission in Crohn's disease (CD) but adherence is challenging. CD-Exclusion Diet (CDED) may be a suitable alternative, but it is structured with mandatory ingredient and requires partial enteral nutrition (PEN). The Tasty&Healthy (T&H) diet excludes processed food, gluten, red meat, and dairy (except for plain yogurt); otherwise, it has no mandatory ingredients and does not require PEN.

Aims & Methods

In this clinician-blinded randomized controlled trial we aimed to assess the tolerability and effectiveness of the T&H diet vs. EEN in children and young adults with CD.
Patients aged 6-25 years with mild-moderate CD were randomized into T&H or EEN for 8-weeks; both groups received weekly dietary support. Explicit nutritional and clinical data, as well as calprotectin were collected at baseline and every 2-weeks thereafter. Tolerability was defined as the discontinuation of the intervention for lack of adherence, or low adherence judged by weekly interviews and 24-hour intake diary. Effectiveness outcomes included clinical remission (i.e. wPCDAI/CDAI), the MINI index that reflects mucosal inflammation (mucosal healing is defined by MINI<8 points), CRP, ESR and calprotectin. Those not tolerating either intervention during the first 24 hours were excluded; otherwise, both ITT and per-protocol (PP) analyses are presented.

Results

Of the 97 randomized patients, 14 were excluded during the first 24 hours and 83 were analyzed, 41 in the T&H arm and 42 in the EEN arm (mean age 14.5±3.7 years). The primary endpoint was met with 36 (88%) patients tolerating T&H vs. 22 (52%) tolerating EEN (OR 6.3 (95%CI 2.2-22; p<0.001).
Week-8 clinical remission rates were similarly high in both groups whether analyzed by ITT (56% in the T&H vs. 38% in the EEN; p=0.1) or PP (67% vs. 76%; p=0.47). The mean MINI index improved significantly from baseline in both the EEN (14.9±5.6 to 7.1±6.1; p<0.001) and T&H (14.5±4.6 to 8.7±6.4; p<0.001) arms, without a difference across groups (p=0.47). In the ITT analysis, MINI<8 at week 8 was higher in the T&H arm (54%) than the EEN arm (41%; OR 2.6 (95%CI 1.1-6.3); p=0.026). Calprotectin decreased significantly from baseline in both arms, without a difference across groups at week-8 (calprotectin <250 was noted in 38% with T&H vs 41% with EEN; p=0.84). There were also no differences between EEN and T&H in ESR and CRP, both improving significantly from baseline (both p<0.01).
There were 3 adverse events reported in this trial with at least possible association with the intervention, all mild, 2 in the EEN arm (nausea and dizziness) and 1 in the T&H arm (constipation).

Conclusion

T&H is a flexible exclusion diet, with similar effectiveness to EEN in mild-moderate CD and higher tolerance. The diet does not include mandatory foods and does not require PEN.

Disclosure

This study was funded by a grant from The Helmsley Charitable Trust

Introduction

Biological treatment in inflammatory bowel disease (IBD) patients is currently hampered by high non-response rates. To enhance personalized medicine and predict response to biological therapeutics such as vedolizumab, the working mechanism should be elucidated. We aimed to visualize macroscopic and microscopic vedolizumab distribution, assess target saturation and detect drug target cells during quantitative fluorescence molecular endoscopy (qFME) to improve understanding of the mechanism of action.

Aims & Methods

Vedolizumab-800CW was developed in-house and GMP produced. Forty-three qFME procedures were performed in thirty-seven IBD patients. Dose escalation was performed using 0.0mg, 4.5mg and 15mg. Subsequently, two patient cohorts were added that received 75mg or 300mg unlabelled vedolizumab prior to vedolizumab-800CW to assess target saturation. Extensive ex vivo analyses were performed to correlate in vivo findings to immune status, fluorescence, microscopic distribution and potential target cells.

Results

Macroscopically and microscopically a significant difference between inflamed and non-inflamed tissue was visualized and quantified (0.0227 and 0.0470 mm^-1, p<0.0001) for the 15 mg cohort. In addition, ex vivo analyses showed a clear dose-dependent increase (p<0.0001) of the fluorescent drug signal, whereas a decrease could be established after adding an unlabelled dose (p<0.0001). Fluorescence microscopy revealed clear membrane binding of vedolizumab-800CW to inflammatory cells and migration into the inflamed mucosa. Various immune cell types were abundantly present in areas with high vedolizumab signal compared to areas with low signal, whereas this was most prominent for plasma cells.

Conclusion

QFME using vedolizumab-800CW enabled visualization and quantification of macroscopic and microscopic vedolizumab distribution in the inflamed target organ. In addition, it showed the potential of qFME to improve understanding in of local drug distribution, target cell identification and target engagement, which could improve understanding of targeted drugs.