Introduction

Monitoring Crohn's Disease (CD) activity is crucial to identify disease progression and tailor treatment. Endoscopic scores are the most reliable tools to monitor disease activity but have some cost and risk implications. Inflammatory faecal biomarkers, such as Faecal Calprotectin (FC), are cost-effective and non-invasive but do not always correlate with endoscopic indexes. There is a need to develop alternative or complementary biomarkers that provide a more accurate assessment of CD activity.

Aims & Methods

The aim of this study was to identify faecal microbial biomarkers that could provide greater performance than FC to monitor activity, leading to improved management of CD.
A cohort of 55 CD patients was recruited from four Spanish hospitals. All participants provided a faecal sample before undergoing colonoscopy, which was analysed for FC levels and microbial markers, including Eubacteria (EUB), Escherichia coli (ECO), Faecalibacterium prausnitzii (FPRA) and its phylogroups I and II (PHG-I and PHG-II), Ruminococcus sp. (RUM), Akkermansia muciniphila (AKK), Methanobrevibacter smithii (MSM), Clostridium cluster I (CLO), Enterococcus sp. (ENT), Roseburia intestinalis (ROS), Clostridium cluster XIV (XIV), and Gammaproteobacteria (GAM). The Simplified Endoscopic Score for Crohn’s Disease (SES-CD) was employed to assess endoscopic activity, being remission and activity defined as SES-CD<2 and SES-CD≥2, respectively.

Results

FC levels showed a significant correlation with SES-CD (r_s=0.778, p<0.001) and a cut-off of 250 μg/g discriminated activity and remission with 86.21% sensitivity, 80.77% specificity, 83.33% positive predictive value, 84.00% negative predictive value, and 83.63% accuracy. The relative abundance of each microbial marker was compared between activity and remission and significant differences were identified in ECO (p<0.001), GAM (p<0.001), MSM (p=0.012), AKK (p=0.024), and RUM (p=0.026). The relative abundance of ECO (r_s=-0.495, p<0.001), GAM (r_s=-0.492, p<0.001), MSM (r_s=0.378, p=0.005) and RUM (r_s=0.274, p=0.042) also showed a significant correlation with SES-CD. None of the microbial markers alone exceeded FC performance. Abundances of microbial markers did not show significant differences when clinical variables such as the Harvey-Bradshaw index, disease location, and body mass index were compared. Only RUM (p=0.011) and ENT (p=<0.001) were found to be significantly different when the sexes were compared, though only in active CD.
The combination of ECO, RUM, GAM, XIV, PHG-I, and PHG-II in a unique microbial signature performed better than FC for discriminating between activity and remission, with 96.57% sensitivity, 96.87% specificity, 95.65% positive predictive value, 96.39% negative predictive value, and 96.25% accuracy.

Conclusion

A new faecal microbial signature has been defined to monitor endoscopic activity in CD with sensitivity, specificity, and accuracy higher than FC. This tool may be useful to improve clinical decision support systems in CD management, optimizing endoscopic allocation and providing a more patient-friendly and cost-effective approach. Further studies are needed to validate these results.

Disclosure

M. Serra-pagès, S. Ramió-Pujol, J. Amoedo, M. Malagón and S. Taboada-López are employees of GoodGut SLU.

Introduction

The PROTDILAT study (Loras et al. Lancet Gastroenterol Hepatol. 2022) at 1-year follow-up showed greater efficacy of EBD vs SEMS for the treatment of short strictures in CD. However, long term efficacy of endoscopic treatmetn is still debated, especially for EDB.

Aims & Methods

Aims: To assess the long-term evolution of patients included in PROTDILAT study. 1). Percentage of patients free of surgery; 2) Factors related to surgery; 3) Need for endoscopic retreatments; 4) Effectiveness related to the type of initial endoscopic treatment (EBD vs SEMS); 5) Complications related to endoscopic or surgical treatment.
Methods: Retrospective study based on PROTDILAT trial database (patients with CD, obstructive symptoms, with stenosis <10cm). Data on medical, endoscopic and surgical treatment and smoking habits were collected. The effectiveness of endoscopic treatment is defined by the percentage of patients free of surgery and endoscopic retreatment at the end of follow-up.

Results

Information available on 80/80 patients (39 SEMS, 41 EBD), 39 women, age (median): 45y (IQR: 38-55); median stricture length 3.4cm (IQR: 2-5.5), 42.5% being anastomotic. Thirty-one percent (25/80) of patients required surgical resection [(median time to surgery 30.61 months (6.35-55.24)). Factors associated to surgery: non-intensification of therapy (HR 0.26 (0.10-0.68)), treatment with EBD exclusively (HR 0.22 (0.08-0.58)) (with respect to treatment with EBD + SEMS) and number of stents (HR 2.31 (1.10-4.84)). Of the 55 patients free of surgery, during the entire follow-up (median 84 months (74.7-84.0)), a median of 2 endoscopic procedures (1-3) were performed: EBD in 45 cases (80.0%) and SEMS in 26 cases (46%). Thirty-eight-point seventy-five percent (31/80 patients) did not require neither surgery nor endoscopic retreatment during the follow-up. The long-term effectiveness of endoscopic treatment was 45% for SEMS and 57.6% for EBD (p=0.374). The complications related to endoscopic or surgical treatment were 8.75% (7/80) versus 36% (9/25) respectively (p=0.002). As for the severity of complications (AGREE/CLAVIEN-DINDO ≥ III), it was observed that surgical treatment presented more severe complications than endoscopic treatment (Endoscopic vs surgical treatment: 38% (3/8) vs 84% (10/12), p=0.011).

Conclusion

Endoscopic treatment (predominantly EBD) avoids surgery in most cases, requiring a low number of endoscopic treatments in the long-term. Patients at higher risk for surgery are those with a greater number of endoscopic treatments that include SEMS and EBD. On the contrary, protective factors are non-intensificationof therapy and having been treated exclusively with EBD. Although there are no significant differences in the long effectiveness between SEMS and EBD, a trend for a better outcome is observed for EBD. To highlight a significant higher rate of complications observed in surgicaltreatment compared to endoscopic treatment.

References

Loras et al. Lancet Gastroenterol Hepatol. 2022

Disclosure

No conflict of Interest