Endoscopic Relapse Risks Evaluation After Ileocolic Resection for Crohn's Disease (RIC-1)

Endoscopic Relapse Risk Factors After Ileocolic Resection on Crohn's Disease Patients in the Biologic Era

Aim of the study:

To evaluate risk factors of endoscopic relapse after ileocolic resection in a cohort of Crohn's disease patients treated with anti-TNF agents.

Methods:

From 2014 to 2022, all consecutive patients who underwent ileocolic resection for Crohn's disease treated with anti-TNF agents in two referral tertiary center were prospectively collected.

Considering exclusion criteria, data from 114 patients were analyzed. The cohort was separated into 2 groups according to study period.

Short and long-term outcomes were compared between the two groups.

Primary outcome:

Endoscopic recurrence (defined as > i2 lesions according to Rutgeerts classification) 6 months after surgery

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Procedure: Ileocolic resection

Detailed Description

Crohn's disease is a chronic inflammatory bowel disease whose preferential location is the ileo-colon, for which surgical management is necessary in 60% of patients.

The most common surgical procedure is ileo-caecal resection for symptomatic last ileal loop stenosis resistant to a well conducted medical treatment.

The conventional surgical technique aims to preserve the length of the digestive tract as much as possible. From a technical point of view, the resection passes as close as possible to the small intestine, leaving the vessels within the mesentery in place.

Despite the improvement of therapeutics (over the last decade, 80% of patients present an endoscopic recurrence at 1 year after surgery. Endoscopic recurrence is defined as the apparition of new typical mucosal lesions based on the Rutgeerts classification.

According to the last ECCO guidelines, biologic agents (TNF-inhibitors, ustekinumab and vedolizumab) are used as maintenance treatment in moderate-to-severe Crohn's disease patients:

• who achieved remission with anti-TNF agents -> maintenance treatment using the same treatment.
• who have achieved long-term remission with the combination of infliximab and immunosuppressants -> monotherapy with infliximab.
• who have achieved long-term remission with the combination of adalimumab and immunosuppressants -> monotherapy with adalimumab. The risk factors for postoperative recurrence are now well established and include smoking habit, penetrating or fistulizing phenotype (classified as B3 in the Montréal classification), perineal disease, history of previous bowel resection, extensive small bowel resection (>20 cm).

Recently, the role of the mesentery in Crohn's disease has been deeply investigated. There is a mesenteric nerve dysfunction with inhibition of anti-inflammatory activity, a major angiogenesis, a multiplication of lymphatic vessels with emboli at the origin of lymphatic drainage abnormalities, a mesenteric hypertrophy with multiple small adipocytes secreting adipokines.

These new elements have raised the question of a potential benefit of a combined resection of the mesentery during an ileocecal resection in the treatment of Crohn's disease.

CALVIN J Coffrey et al. carried out a study in 2008 comparing a prospective cohort with ileo-caecal resection including the mesentery (mesentery resection group) to a retrospective cohort with classical ileocecal resections (ICR group). The results were very promising in terms of recurrence requiring surgical management with a re-operation rate at 5 years of 40% in the classical ICR group vs 2.9% in the mesenteric resection group. And shows that significant mesenteric disease is an independent risk factor for recurrence with a HR=4.7 (p<0.007).

Thus, it is necessary to analyse within local patient base: the percentage of endoscopic recurrence at 6 months after surgery in patients treated with anti TNFa as well as the risk factors at the origin of the increase of these recurrences, more particularly the anatomopathological factors which could call into question the surgical practices within the long term a major interest in resection of the mesentery.

Therefore, the investigator carried out a retrospective study in two referral tertiary center, Montpellier University Hospital and Nîmes University Hospital. The investigator prospectively collected data from 2014 to 2022 from Crohn's disease patients treated with TNF inhibitors who have undergone ileocolic resection, to determine the percentage of endoscopic recurrence at 6 months and its risk factors.

• Study Type: Observational
• Enrollment (Actual): 133

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Montpellier University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All patients with Crohn's disease treated with TNF inhibitors who underwent ileocolic resection between 2014 and 2023 in the Digestive Surgery (A), Oncology and Minimally Invasive Department (Pr FABRE) of the Montpellier University Hospital and the Digestive Surgery and Cancer Department (Pr PRUDHOMME) of the Nimes University Hospital

Description

Inclusion Criteria:

• Patients with histologically proven Crohn's disease
• On anti-TNF alpha: infliximab, adalimumab (ECCO 2014 recommendation)
• > 18 years old patients
• All patients who have undergone ileocolic resection and whose disease site is accessible to endoscopic follow-up (first or repeat procedure)

Exclusion Criteria:

• Minor patients under 18 years of age
• Endoscopic follow-up not possible
• Pregnant women
• Medical treatment other than anti-TNF alpha

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Crohn's disease patients undergoing ICR; Crohn's disease patients undergoing ICR treated with TNF inhibitors	Procedure: Ileocolic resection; Ileocolic resection by open or laparoscopic approach

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic recurrence rate	Defined as the presenc of new mucosal lesions classified >i2 according to Rutgeerts classification.	6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resection margins	Pathological examination of resection margins	90 days after surgery
Length of resected specimen	Pathological examination and measure of the lenght of ileon and colon resection	90 days after surgery
Duration of surgery	Operative time	90 days after surgery
Intra-operative blood loss	Intra-operative blood losss	90 days after surgery
Postoperative morbidity rate	Postoperative morbidity according to Clavien Dindo	90 days after surgery
Mortality rate	Death occuring within 90 days after surgery	90 days after surgery
Myenteric plexitis	Myenteric plexitis defined as the presence of > 3 inflammatory cells in myenteric plexuses of the proximal resection margin	90 days after surgery
Number of inflammatory cells in myenteric plexuses	Number of inflammatory cells in myenteric plexuses of inflammatory cells in myenteric plexuses	90 days after surgery

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Carémeau University Hospital, Nîmes
• Investigators: Principal Investigator: Thomas BARDOL, MD, MSc, Montpellier University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: RECHMPL23_0187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No