Introduction

The Crohn's Disease Exclusion Diet (CDED) is a dietary approach that exclude specific foods to induce remission in Crohn's disease (CD).

Aims & Methods

We conducted an open-label, randomized controlled trial including adults with mild-to-moderate CD, as determined by the Harvey-Bradshaw Index (HBI). Patients were randomly assigned to either CDED or a control diet (Mediterranean pattern). At enrollment, we collected demographic data and medical histories. We measured weight, body mass index (BMI), HBI, fecal calprotectin, and serum inflammatory markers at baseline, 12 and 24 weeks. Bioelectrical impedance analysis (BIA) evaluated safety for CDED participants. The primary outcome was clinical remission (HBI<5), measured in the intention-to-treat population. This study aims to provide a real-world evidence.

Results

Twenty-four patients were randomized to the CDED diet and 21 to the control group, without significant differences at baseline. Five CDED participants discontinued the diet for intolerance by a median of 5 weeks. After 12 and 24 weeks, CDED patients showed significantly lower HBI and higher remission rates compared to control group (70.8% vs 38.1% at 12 weeks and 79.2% vs 42.9% at 24 weeks; p=0.027 and p<0.0001, respectively). Fibrinogen resulted significantly lower in CDED than control group at week 24. CDED participants reported a median BMI reduction from 25.8 kg/m² to 24.4 kg/m² at 12 weeks and 24.5 kg/m² at 24 weeks (p=0.047), although BIA analysis indicated a reduction in fat mass after 12 and 24 weeks (p<0.001 and p<0.001, respectively) while fat-free mass and body cellular mass significantly increased at 12 weeks (p=0.001 and p=0.042, respectively) and remained stable at 24 weeks (p=0.072 and p=0.120, respectively).

Conclusion

The CDED has proven to be safe and effective for achieving remission in adults with mild-to-moderate CD.

Disclosure

No conflict of interest to disclose

Introduction

While ileocecal resection (ICR) is the most common surgical procedure in Crohn's disease (CD), non-ICR surgeries account for only 20% of cases and remain underrepresented in the literature. This study aimed to identify specific clinical risk factors for surgical recurrence in CD patients undergoing small bowel or colonic resections without involving the ileocecal valve.

Aims & Methods

This multicenter retrospective cohort study included 257 patients with CD (124 small bowel resections, 133 colonic resections) across 13 Italian centers from 1978 to 2023. Univariate and multivariate logistic regression and Cox proportional hazards analyses were performed to identify clinical risk factors associated with surgical recurrence.

Results

The cohort comprised two distinct groups: small bowel resections (n=124), characterized by male predominance (63.71%), a high prevalence of stricturing disease (60.48%), and a median follow-up of 75.5 months; and colonic resections (n=133), featuring a more balanced gender distribution (47.37% male), higher rates of penetrating disease (47.37%), and a median follow-up of 88.0 months. Penetrating disease behaviour emerged as the only significant predictor of recurrence in logistic regression analysis (OR 2.16, 95% CI 1.03-4.52, p=0.041), while factors typically predictive in ICR, such as smoking (OR 0.90, p=0.843) and prior resections (OR 0.96, p=0.913), were non-significant. Cox regression identified prior biologic exposure as a significant predictor of earlier recurrence (HR 2.52, 95% CI 1.22-5.18, p=0.012), with TNF experience specifically associated with increased risk (HR 2.28, 95% CI 1.12-4.67, p=0.024). The cumulative number of risk factors (HR 1.35, 95% CI 1.01-1.82, p=0.046) and postoperative intra-abdominal septic complications (HR 2.75, 95% CI 1.18-6.44, p=0.020) also contributed to recurrence risk. Disease phenotypes significantly differed between resection types (p<0.001), with stricturing disease most prevalent in small bowel resections (60.48% vs. 36.09% in colonic) and penetrating disease more common in colonic resections (47.37% vs. 36.29% in small bowel). Results are summarized in Table 1.

Table 1: Univariate logistic regression analysis of predictors for postoperative surgical recurrence in patients undergoing small bowel or colonic resections. Abbreviations: CI: Confidence Interval; CD: Crohn’s Disease; IBD: Inflammatory Bowel Disease; POR: Postoperative recurrence; TNF: Tumour Necrosis Factors.

Conclusion

This study reveals distinct risk factors for surgical recurrence after non-ICR surgeries in CD. Unlike ICR where smoking, perianal disease, and prior resections predominate, non-ICR recurrence is primarily associated with penetrating disease phenotype and prior biologic exposure. These findings demonstrate that risk stratification models developed for ICR are not applicable to non-ICR surgeries, highlighting the need for procedure-specific approaches to postoperative management. Tailored prophylactic strategies should address the unique recurrence dynamics of small bowel and colonic resection surgeries.

Introduction

Ustekinumab (UST) is efficacious in inducing and maintaining remission in patients with Crohn’s disease (CD). Treatment persistence up to 5 years has been documented in open-label extension of pivotal RCTs of UST (1). In a prospective, real-world (RW) nation-wide study (REASSURE) 73% of 169 bio-naive (BN) and bio-experienced (BE) patients were still in the study after 2 years of treatment with UST (2).

Aims & Methods

In this prospective, single-centre study we aimed to assess the long-term persistence of UST treatment in consecutive BN and BE CD patients who were treated in RW setting with UST in approved dosing regimens for induction and remission maintenance.
Consecutive BN and BE CD patients with active moderate to severe luminal CD with or without perianal involvement, aged 18-80 years who received UST induction (6mg/kg iv) and maintenance (90mg sc q8 weeks) and achieved clinical and biomarker response or remission without concomitant steroids at 6 months after initiation of UST were included in a long-term observational study. Study end-point was treatment discontinuation for whatever reason. Patients were followed every 4 months with clinical examination, recording of the Harvey-Bradshaw Index (HBI) and laboratory tests [including regular CRP and occasional Fecal Calprotectin (FC)]. Ileocolonoscopy was performed at 6 months after initiation of treatment and then every 2 years. Clinical response and remission were defined as a drop in HBI ≤2 and <5 from initiation of treatment, respectively. Biomarker remission was defined as a CRP level ≤0.5mg/dL and FC ≤200 μg/g. Endoscopic remission was defined as a SES-CD score of ≤3 and a Rutgeert’s score of ≤1 for patients with inflammatory CD and for patients in post operative setting, respectively. In this abstract we report the results on the persistence of UST-treatment based on clinical and biomarker data.

Results

Between 1/6/2017 and 31/12/2024, 64 patients were evaluated and 52 patients who fulfilled the entry criteria were enrolled in the study. Patient demographic, clinical, biomarker and endoscopic data is shown in table 1. Of these 52 patients, 42 (80.7%) patients were still maintained in clinical, biomarker and endoscopic remission [HBI 2.3 (1-4), mean (range), CRP<0.5 mg/dL and FC <200μg/ml)] on UST 90 mg sc every 8 weeks for >2 [n=10 (24%),3 [n=5 (12%)], 4 [n=5 (12%)], 5 [n=6 (14%)] και ≥ 6 [n=16 (38%)] years after inclusion in the study, respectively. Treatment escalation was not performed and neither serious adverse events nor serious infections were reported in any of these patients during the study period. Ten patients (19.3%), two BN and 8 BE stopped therapy. Cessation of treatment was slightly statistically higher in BE than PN patients (p<0.05). Five of 10 patients stopped treatment because of post-operative endoscopic recurrence (Rutgeert’s score ≥i2) at 2,2,2.5, 2.9 and 3.2 years, respectively and 2 patients because of a flare of colitis at 4 and 6.5 years, respectively after inclusion in the study. Another 3 patients stopped therapy because of active axonal spondyloarthropathy 2.3 years (n=1) and two patients because they were diagnosed with pancreatic cancer and a T1-colorectal cancer (patient was on the 3nd biologic agent after a 20-year course of colitis) after 7 years in the study, respectively.

Conclusion

This prospective, open label, single-center RW study confirms the long-term treatment persistence of UST with an acceptable safety profile.

References

1. Colombel JF, et al, Clin Gastroenterol Hepatol. 2023;S1542-3565(23)00499-8
2. Mantzaris GJ et al, UEGW 2024, MP676.

Disclosure

Advisory Boards/Lectures: AbbVie, Aenorasis, Celgene, Celltrion, Dr Falk Pharma, Ferring, Hospira, Inovis, Janssen, Merck Sharp & Dohme, MYLAN, Pfizer, Takeda, και Vianex
Research support: AbbVie, Ferring, Galenica, Genesis, Merck Sharp & Dohme, MYLAN, Takeda και Vianex

Introduction

Prevention of postoperative recurrence (POR) after ileocolonic resection is one of the most relevant issues in the management of Crohn's disease (CD). The role of ustekinumab (UST) especially in the context of real-life studies is still not entirely clear, often due to small sample sizes, thus requiring further investigation and confirmation (1).

Aims & Methods

Our real life single-centre retrospective study aims to evaluate the effect of UST therapy on prophylaxis of endoscopic recurrence after ileo-colonic resection in CD. In the whole cohort UST was used as first-line therapy for prophylaxis of recurrence. All patients (pts) underwent the first endoscopic evaluation within 6-12 months after surgery to assess postoperative recurrence (POR), using the Rutgeerts score and were subsequently evaluated at 22 (+-3) months with a second endoscopy. Persistence on therapy ~ two years after the surgery was also evaluated.

Results

27 pts with a mean age of 51 years old were included. 40% of pts had previously been resected and 45% were active smokers. 93% had already been exposed to one or more biological drugs. The most frequent reason for surgery was the presence of stenosing disease. The first postoperative colonoscopy at 6-12 months, showed severe POR (RS score i3 or i4) in 19% of patients, so 11% changed treatment at this time point. Among patients who continued the drug (24 pts), the second endoscopy performed at 22 (+-3) months showed severe POR in 13% of pts, whose treatment was subsequently changed.
At ~ 2 years persistence on therapy in the cohort was 78%, notably endoscopic remission (RS<2) was found in 37%.
No patients discontinued the drug due to adverse effects.

Conclusion

In our real life cohort of complex CD patients, ustekinumab showed high levels of persistence on therapy at the point of time considered, although less than half of the patients achieved endoscopic remission.

References

1- Tursi A, Mocci G, Picchio M, Elisei W, Maconi G. Letter: ustekinumab for the treatment of post-surgical and refractory Crohn's disease. Aliment Pharmacol Ther. 2021 Apr;53(7):859-860. doi: 10.1111/apt.16281. PMID: 33709395.

Disclosure

No