Introduction

The Rutgeerts score, developed three decades ago, is used to assess postoperative endoscopic recurrence in patients with Crohn’s disease (CD) following ileocolonic resection with an end-to-end anastomosis.¹ However, contemporary surgical techniques have introduced new anatomical locations – the ileal body and ileal inlet – which were not accounted for in the original Rutgeerts score.² Additionally, the original Rutgeerts score has demonstrated limited inter-observer reliability.³ To address these limitations, an updated Rutgeerts score, incorporating new anatomical sites, has been proposed. According to the updated Rutgeerts score lesions restricted to the ileal inlet, or the ileal body can no longer be scored as i2a.² While the updated Rutgeerts score offers improved assessment of inflammation after an ileocolonic resection, its reproducibility has not yet been validated.

Aims & Methods

The aim of our study was to evaluate the inter- and intra-observer reliability of the updated Rutgeerts score.
We conducted a retrospective analysis of 183 patients with CD (48% male, median age 36.8 years) who underwent video-recorded ileocolonoscopy within 14 months of resection with ileocolonic anastomosis. An expert reader MF selected and scored videos of ileocolonoscopies, which were then used as the gold standard. After receiving a two-hour training with a set of ten videos eight expert gastroenterologists reviewed and scored the videos. Each reader assessed 92 videos, including 23 videos that were re-scored after at least one month. Based on the gold standard, inter- and intra-rater agreement was calculated across all score levels and for each score level. Inter-rater reliability was assessed using Fleiss' kappa, and intra-rater reliability using Cohen’s kappa, both with and without application of linear weights.

Results

The probability of perfect agreement between two readers across all scores was 0.604 (95% CI: 0.559-0.649). The chance-corrected inter-observer agreement based on Fleiss’ kappa with linear weights across all scores was 0.619 (95% CI: 0.562-0.676). The strongest inter-observer agreement was observed for the i2a score, with a value of 0.736 (95% CI: 0.647-0.826), while the weakest was seen for the i1 score (0.357, 95%CI: 0.225-0.489).
Intra-rater reliability with a Cohen’s kappa was 0.688 (0.609-0.767), and with weighted kappa was 0.831 (0.758-0.868). The overall agreement rate was 76.0% (69.1%-82.0%).

	Categorical		Ordinal
	Estimate	95%CI	Estimate	95%CI
All levels	0.604	(0.559;0.649)	0.882	(0.866;0.897)
i0	0.633	(0.467;0.800)	0.884	(0.824;0.945)
i1	0.357	(0.225;0.489)	0.829	(0.758;0.899)
i2a	0.736	(0.647;0.826)	0.925	(0.896;0.954)
i2b	0.502	(0.439;0.566)	0.856	(0.834;0.877)
i3	0.487	(0.351;0.623)	0.859	(0.798;0.920)
i4	0.715	(0.606;0.824)	0.894	(0.854;0.934)

Table 1. Summary of agreement across score levels: Agreement for all scores and by individual score levels, based on the gold standard (defined as the scores given by an expert reader MF). Categorical agreement reflects only perfect agreement. Ordinal agreement applies linear weights, assigning less weight to minor disagreements and more to larger ones.

Conclusion

The updated Rutgeerts score demonstrates good agreement and substantial inter- and intra-rater reliability in assessing postoperative endoscopic recurrence in CD, supporting its potential for broader adaptation in both clinical practice and research settings.

References

1. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99(4):956-963. doi:10.1016/0016-5085(90)90613-6
2. Rivière P, Bislenghi G, Vermeire S, et al. Postoperative Crohn’s Disease Recurrence: Time to Adapt Endoscopic Recurrence Scores to the Leading Surgical Techniques. Clin Gastroenterol Hepatol. 2022;20(6):1201-1204. doi:10.1016/j.cgh.2022.02.025
3. Marteau P, Laharie D, Colombel JF, et al. Interobserver Variation Study of the Rutgeerts Score to Assess Endoscopic Recurrence after Surgery for Crohn’s Disease. Journal of Crohn’s and Colitis. 2016;10(9):1001-1005. doi:10.1093/ecco-jcc/jjw082

Introduction

Mirikizumab is an anti-IL-23p19 monoclonal antibody, a key mediator in the pathogenesis of inflammatory bowel diseases. We evaluated the induction efficacy and safety of mirikizumab in the LUCENT-1 (NCT03518086) Chinese subpopulation.

Aims & Methods

In this Phase 3, multi-center, randomized, parallel-arm, double-blind, placebo-controlled trial, conventional-failed or biologic/tofacitinib-failed Chinese adult patients (N=184) with moderately to severely active ulcerative colitis (UC, Modified Mayo Score 4-9, endoscopic subscore ≧2) were randomized in a 3:1 ratio to 300 mg mirikizumab (intravenous) or placebo every 4 weeks for 12 weeks. Randomization was stratified by biologic/tofacitinib failure status, baseline corticosteroid use and baseline disease activity (Modified Mayo Score). The primary objective was to test the hypothesis that mirikizumab was superior to placebo in inducing clinical remission at Week 12 (W12). Key secondary endpoints included alternate clinical remission, clinical response, clinical response in biologic-failed patients, symptomatic remission, endoscopic remission, histologic-endoscopic mucosal and bowel-movement urgency improvement. Analyses in Chinese subpopulation were descriptive. Missing data was imputed as non-responders for the categorical endpoints. Bowel urgency change from baseline data was reported based on Mixed Model Repeated Measured.

Results

Baseline characteristics were balanced across groups. A greater proportion of mirikizumab-treated patients achieved clinical remission (18.6% vs. 7.0%; Δ=11.5 [95%CI: 1.7, 21.3]) and alternate clinical remission at W12 (21.4% vs. 7.0%; Δ=14.3 [95%CI: 4.4, 24.2]). Mirikizumab also improved key secondary endpoints at W12. The frequencies of treatment-emergent adverse events were similar between groups (mirikizumab [60.0%] vs. placebo [62.8%]). There were fewer serious adverse events (10 [7.1%] vs. 7 [16.3%]) and discontinuations due to adverse events (2 [1.4%] vs. 3 [7.0%]) in mirikizumab-treated patients compared to placebo. There was 1 adenocarcinoma of colon (mirikizumab group) and no deaths during the treatment period.

Table 1: Primary and key secondary outcomes of LUCENT-1 in Chinese population	Placebo IV N=43	Miri 300 mg IV N=140
Clinical Remission at Week 12, n (%) Common risk difference vs placebo	3 (7.0)	26 (18.6) 11.5
Alternate Clinical Remission at Week 12, n (%) Common risk difference vs placebo	3 (7.0)	30 (21.4) 14.3
Clinical Response at Week 12, n (%) Common risk difference vs placebo Clinical Response (biologic-failed) at Week 12, n (%) Common risk difference vs placebo	13 (30.2) 3 (13.0)	76 (54.3) 23.2 32 (45.1) 32.0
Endoscopic remission at Week 12, n (%) Common risk difference vs placebo	5 (11.6)	44 (31.4) 19.0
HEMI at Week 12, n (%) Common risk difference vs placebo	2 (4.7)	24 (17.1) 12.6
Symptomatic remission at Week 4, n (%) Common risk difference vs placebo	5 (11.6)	15 (10.7) -1.6
Symptomatic remission at Week 12, n (%) Common risk difference vs placebo	8 (18.6)	49 (35.0) 16.2
Urgency Numeric Rating Scale (NRS), LSM (SE) LSM difference vs placebo	-1.6 (0.4)	-2.0 (0.2) -0.39
CI = confidence interval; IV = intravenous; LSM = least squares mean; Miri = mirikizumab; SE = standard error. Modified Intent-to-Treat population. Number of biologic-failed patients in placebo and Miri groups were 23 and 71, separately. Clinical remission: Stool frequency (SF) subscore = 0 or 1 with a ≥1-point decrease from baseline, and Rectal bleeding (RB) subscore = 0, and Endoscopic subscore (ES) = 0 or 1 (excluding friability) Alternate clinical remission: SF subscore = 0 or 1, RB subscore = 0, and ES = 0 or 1 (excluding friability) Clinical response: decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and decrease of ≥1 point in the RB subscore from baseline or an RB score of 0 or 1 Clinical response (bio-failed): clinical response in patients who had previously failed biologic or tofacitinib therapy Endoscopic remission: ES = 0 or 1 (excluding friability) HEMI (histologic-endoscopic mucosal improvement): Histologic improvement, defined using Geboes scoring system with neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue; and endoscopic remission Symptomatic remission: SF = 0, or SF = 1 with a ≥1-point decrease from baseline and RB = 0 Urgency NRS (numeric rating scale) ∆ baseline: least square mean change in urgency NRS from baseline Mixed Model for Repeated Measures (MMRM) was used to compare the treatment groups for bowel movement urgency improvement; for all other endpoints, the Cochran-Mantel-Haenszel (CMH) test with missing data imputed as nonresponse, was used to compare the treatment groups while adjusting for the stratification factors. All analyses in Chinese subpopulation were for descriptive purpose, and multiplicity adjustment was not applied.

Conclusion

Efficacy and safety profiles were consistent with LUCENT-1 overall population, supporting benefits of mirikizumab treatment in the Chinese UC patients.

Disclosure

No conflict of interest to disclose

Introduction

Faecal microbiota transplantation (FMT) is an emerging therapy in inflammatory bowel disease (IBD), supported by evidence for improved clinical and endoscopic outcomes. Decontamination of the recipient gastrointestinal tract using antibiotics or colonic lavage has been proposed to improve FMT efficacy by reducing microbial load and creating a niche for donor organism colonisation. The aim of this study was to assess the effects of antibiotic pre-treatment and colonic lavage on clinical and endoscopic outcomes of FMT in IBD.

Aims & Methods

A systematic review of the literature was conducted by searching PubMed, MEDLINE and Scopus from inception to July 2024. Prospective studies examining FMT in IBD with or without antibiotic pre-treatment and/or colonic lavage were included. Outcomes included clinical response, clinical remission, endoscopic response and endoscopic remission. A random-effects model was used to calculate pooled proportions with 95% confidence intervals (CI).

Results

Forty-one studies (n=1185) were included, of which 7 (17.1%) incorporated antibiotic pre-treatment and 29 (70.7%) incorporated colonic lavage prior to FMT therapy. Eight studies (19.5%) were in Crohn’s disease, 32 (78%) were in ulceratice colitis and one study incorporated any IBD. Antibiotic pre-conditioning courses varied in terms of antibiotics used, treatment duration and washout period prior to FMT. Polyethylene glycol was the most used lavage preparation (23 studies, 79.3%). Antibiotic pre-treatment was associated with numerically higher rates of clinical response (64% vs. 56%), clinical remission (47% vs. 39%), endoscopic response (59% vs. 45%) and endoscopic remission (47% vs. 21%) than no antibiotics, but these differences did not reach statistical significance. Colonic lavage was associated with significantly lower clinical response (52% vs. 71%) compared to no lavage. Clinical remission rates were numerically lower in the lavage group (37% vs. 46%), but again, not statistically significant. Endoscopic response and remission rates were similar. Risk of bias was high or moderate in most studies.

Outcome (%; 95% CI)	Antibiotics	No antibiotics	Lavage	No lavage
Clinical response	64% (52-76%)	56% (48-64%)	52% (43-60%)	71% (62-80%)
Clinical remission	47% (30-63%)	39% (31-47%)	37% (28-47%)	46% (29-63%)
Endoscopic response	59% (44-74%)	45% (24-66%)	51% (30-71%)	45% (16-74%)
Endoscopic remission	47% (25-70%)*	21% (11-31%)	22% (10-33%)	22% (10-35%)

*Single study in antibiotic group. Bold = statistically significant difference.

Conclusion

The results of this review suggest while antibiotics may improve FMT outcomes in IBD, the evidence remains inconclusive, and further adequately powered studies are needed before changing clinical practice. Colonic lavage appears to reduce clinical response to FMT and should be avoided where feasible. FMT delivery methods that avoid the need for bowel preparation, such as capsules, enemas or upper gastrointestinal administration should be considered preferable.

Disclosure

RV Bryant, SP Costello and E Tucker are shareholders in BiomeBank.

Introduction

Janus kinase inhibitors (JAKi) exhibit distinct performance characteristics versus monoclonal antibody (mABs) biological agents in the management of ulcerative colitis (UC). There is a lack of direct comparative effectiveness data of JAKi small molecules versus mABs in the real world.

Aims & Methods

In the absence of direct head-to-head comparisons, we determined the persistence of tofacitinib (TOF) versus vedolizumab and tumour necrosis factor inhibitor (TNFi) mABs in advanced therapy (AT)-naïve and AT-exposed real-world UC subjects from a population-based prospective registry.

The Persistence Australian National IBD Cohort (PANIC5) registry collected AT prescribing data for the entire Australian population up until Dec 2021. In Australia, all advanced therapies for IBD are prescribed without a hierarchical order in subjects with moderate-severe UC refractory to conventional therapies, irrespective of occupation and insurance status. Treatment is provided indefinitely in those that enter into clinical remission. Non-persistence was defined as failure to continue AT prescriptions for >6-months. Propensity score matching (PSM) statistically controlled for baseline selection biases. Kaplan-Meier survival curves were generated for AT persistence and compared using the log-rank test. Cox proportional hazards regression models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI). P<0.05 was deemed statistically significant (SPSS, USA).

Results

A total of 9,671 consecutive UC patients were recruited (53% male, 23,348 patient-years of follow up). The cohort comprised 14,772 treatment lines: 6,044 infliximab (IFX), 1,981 adalimumab (ADA), 5,467 vedolizumab (VED), 750 golimumab (GOL) and 530 tofacitinib (TOF). TOF exhibited superior persistence versus IFX (HR: 1.88, 95%CI: 1.34-2.63, P<0.001), ADA (HR: 2.10, 95%CI: 1.49-2.94, P<0.001) and GOL (HR: 2.20, 95%CI: 1.55-3.11, P<0.001) but not versus VED (HR: 1.28, 95%CI: 0.92-1.80, P=0.14). Following PSM, TOF was not significantly higher in persistence compared to mABs among AT-naïve subjects (all P>0.05). However, TOF showed superior persistence compared to all mABs among AT-exposed (all P<0.001). The persistence of TOF (P=0.77) did not significantly decline moving from AT-naive- to AT-exposed treatment status, unlike for TNFi (-8 months) and VED (-19 months, both P<0.001). PSM-multivariate Cox regression showed predictors of higher persistence to be use of TOF, AT-naïve status, use of immunomodulator. Rankings of persistence of ATs are presented for AT-naïve- and AT-exposed UC subjects (Table).

Advanced therapy naive				Advanced therapy exposed
Rank	Drug	HR (95%CI)	P	Rank	Drug	HR (95%CI)	P
1	vedolizumab	0.87 (0.45-1.68)	0.68	1	tofacitinib	1	ref
2	tofacitinib	1	ref	2	vedolizumab	2.12 (1.43-3.15)	<0.001
3	infliximab	1.42 (0.74-2.76)	0.29	3	infliximab	2.83 (1.90-4.21)	<0.001
4	golimumab	1.48 (0.76-2.90)	0.24	4	adalimumab	3.09 (2.07-4.61)	<0.001
5	adalimumab	1.55 (0.80-2.99)	0.19	5	golimumab	3.49 (2.31-5.49)	<0.001

Conclusion

This is the first real-world study comparing treatment effectiveness using a national universal insurance persistence dataset. It found that tofacitinib had significantly greater persistence than biological agents in patients with ulcerative colitis who had previously received advanced therapy. Unlike monoclonal antibodies, tofacitinib did not show a decline in persistence after exposure to advanced therapy. Given these findings, JAK inhibitors like tofacitinib should be strongly considered for patients switching advanced therapies in ulcerative colitis.

Disclosure

RL advisory board: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grants: Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, MRFF

Introduction

Intestinal barrier integrity is emerging as a key therapeutic target in inflammatory bowel disease (IBD). Advanced endoscopic imaging techniques, including ultra-high magnification endocytoscopy (ECS) and probe-based confocal laser endomicroscopy (pCLE), enable real-time, in vivo structural and functional intestinal barrier assessment. Raman Spectroscopy (RS) can add a molecular dimension through vibrational fingerprinting of barrier-associated metabolites in biological samples.¹

Aims & Methods

This study explores the potential of RS integration with advanced endoscopy to characterise the intestinal barriers in IBD, targeting on tryptophan-derived metabolites and carbohydrates. A total of 46 IBD patients [25 Crohn’s disease (CD) and 21 ulcerative colitis (UC)] and 7 healthy controls (HC) undergoing endoscopic assessment or surveillance were prospectively enrolled from two academic centres. ECS or pCLE were used to evaluate epithelial and vascular barrier integrity. Barrier healing was defined as ECS score ≤ 1 or pCLE score ≤ 4, with preserved villi/crypt architecture, normal vasculature, and also absence of fluorescein leakage for pCLE. Advanced endoscopy-guided biopsies were collected from representative bowel segments. Mucosal healing (MH) was assessed by experienced pathologists using Nancy’s Histological Index ≤1. Epithelial (Claudin-2 and ZO-1) and vascular (PV-1 and CD-31) barrier markers were analysed through confocal microscopy, and their expression was automatically quantified using QuPath. Micro-RS was applied to tissue samples and matched sera to measure key tryptophan metabolites (kynurenine, indolepropionic acid, and melatonin) and carbohydrates.^2,3 Six-month major adverse outcomes (MAOs) were recorded. Group differences in Raman spectra were analysed with the Mann-Whitney test; correlations were assessed via Pearson’s test.

Results

Among patients undergoing ECS, barrier healing was observed in 10/22 (45%) colonic and 6/9 (67%) ileal cases. pCLE-based assessment revealed healing features in 5/16 (31%) colonic and 2/15 (13%) ileal evaluations. Raman spectral analysis showed a significant (p<0.05) reduction in tryptophan metabolites and carbohydrate-associated peaks in IBD tissues and sera compared to HC, especially in inflamed patients. When stratified by advanced endoscopy-identified barrier integrity, tryptophan metabolites -known barrier modulators-, and carbohydrates -likely reflecting mucin barrier layer- were markedly reduced (p<0.05) in patients with impaired barrier function. Notably, tryptophan derivatives positively correlated with Claudin-2 and ZO-1 in UC (r>0.4), and with PV-1 in CD (r>0.5). Similarly, carbohydrates correlated positively with Claudin-2 in UC (r=0.4) and negatively with CD-31 in CD (r=-0.4). Lower levels of indolepropionic acid and carbohydrates correlated with worse short-term MAOs (r<-0.4).

Conclusion

The integration of RS with advanced endoscopic images offers a novel, multi-layered approach to assess intestinal barrier integrity in IBD. RS can identify novel non-invasive biomarkers of mucosal and barrier healing, with potential real time applications for monitoring disease activity and predicting therapeutic outcome. Tryptophan metabolites may serve as a predictive biomarker of barrier healing paving the way toward personalised, barrier-targeted therapies.

References

1 Smith SCL, Banbury C, Zardo D, et al. PLoS One 2021; 16: e0252210.
2 Michaudel C, Danne C, Agus A, et al. Gut 2023; 72: 1296–307.
3 Arras W, Breugelmans T, Oosterlinck B, et al. J Crohns Colitis 2025; 19.

Introduction

Increased mesenteric blood flow in inflammatory bowel disease (IBD) alters biomechanical forces acting on intestinal vascular endothelial cells (ECs). These cells sense mechanical stimuli through the mechanosensitive ion channel Piezo1, which transduces these forces into pro-inflammatory signaling, thereby aggravating inflammation. Moreover, lactate contributes to immune regulation by influencing macrophage polarization. However, the precise role of Piezo1 in governing endothelial lactate metabolism during IBD pathogenesis remains insufficiently understood.

Aims & Methods

To elucidate the role of Piezo1 in IBD, single-cell RNA sequencing was conducted on colonic tissues from IBD patients and healthy controls to evaluate Piezo1 expression and its association with lactate metabolism. Endothelial cell-specific Piezo1 knockout (Piezo1^ΔEC/ΔEC) mice were generated and subjected to DSS-induced colitis to assess inflammation severity, lactate levels, and macrophage polarization. CRISPR-Cas9 technology was employed to knock out Piezo1 in human umbilical vein endothelial cells (HUVECs). The involvement of the HIF-1α-mediated glycolysis pathway and monocarboxylate transporter 1 (MCT1) in Piezo1-dependent lactate regulation was also investigated.

Results

Piezo1 expression was significantly upregulated in intestinal ECs from active IBD patients and DSS-induced colitis mice compared to controls. Single-cell sequencing further confirmed the enrichment of Piezo1 in intestinal ECs during active inflammation. In DSS-induced colitis, Piezo1^ΔEC/ΔEC mice exhibited decreased levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β), a reduced M1/M2 macrophage ratio, and lower lactate concentrations in both endothelial cells and plasma. Piezo1 activation promotes aerobic glycolysis through the Ca²⁺-induced CaMKII-HIF1α axis. Moreover, the Piezo1/HIF-1α pathway upregulated MCT1 expression in ECs, enhancing lactate transport across mesenteric vessels. Deletion of Piezo1 suppressed MCT1 expression, normalized plasma lactate levels, attenuated M1 macrophage activation, and ameliorated colitis severity in Piezo1^ΔEC/ΔEC mice.

Conclusion

These findings demonstrate that mechanical forces activate Piezo1 in intestinal ECs, driving lactate metabolism through the Piezo1-HIF-1α-MCT1 axis and promoting M1 macrophage differentiation, which subsequently contribute to intestinal inflammation in IBD. Targeting Piezo1 may represent a promising therapeutic strategy for the treatment of IBD.