Introduction

The CACTUS-CD study (NCT06125678) prospectively evaluated 407 patients with small bowel Crohn’s disease (CD) and demonstrated that intestinal ultrasound (IUS), particularly smal intestinal contrsat ultrasound (SICUS), could approach the diagnostic accuracy of computed tomography enterography (CTE) and magnetic resonance enterography (MRE)[1]. The value of IUS/SICUS in monitoring of known CD in reference to device assisted enteroscopy (DAE) is not known [2].

Aims & Methods

This post hoc analysis aimed to compare these imaging modalities (IUS, SICUS, CTE/MRE) against DAE for lesion localization and stricture detection in a subset of patients.
Forty-eight patients with established small bowel CD underwent IUS, CTE or MRE, and DAE within one week. Segmental localization (proximal, mid, distal) was assessed across all modalities. Strictures on IUS were defined using wall thickness >3 mm, luminal narrowing <1 cm, and pre-stenotic dilatation[3]. Simplified Magnetic Resonance Index of Activity (MARIA) for MRE, International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) for IUS, and modified Simple Endoscopic Score for Crohn’s Disease (SES-CD) score (0-12, based on ileal subscore) for DAE were compared [2,4,5].

Results

The median age was 42 years (range 18–73), with 43.8% female and a median BMI of 21 kg/m². Among MRE patients (n=22), the median simplified MARIA (Magnetic Resonance Index of Activity) score was 4.5 (range 1-5). IUS revealed a median bowel wall thickness of 5.55 mm (range 2.2-8.6), an median International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) of 63.3 (8.8-87). For DAE, modified Simple Endoscopic Score for Crohn’s Disease (SES-CD) median score was 9 (0-11). Technical success of DAE was 46/48 (95.8%, technical failure: both post operative). The approach of DAE was antegrade (n=16), retrograde (n=26) and bidirectional (n=6). Median depth of maximal insertion was 120 cm (30-600 cm) with median time ​30 minutes (10-240).
All modalities had 100% agreement in distal bowel.In mid-bowel, CTE/MRE and DAE were fully concordant; IUS achieved 72.7%. Proximal agreement was 71.4% for CTE/MRE and 57.1% for IUS. For strictures, CTE/MRE yielded the highest sensitivity (81%), specificity (88%), and agreement (kappa 0.65). IUS had lower sensitivity (47%) but excellent specificity (94%). SICUS performed better than IUS with sensitivity of 75% (p=0.039) and kappa 0.62. Spearman’s correlation showed stronger association of MARIA with SES-CD (r = 0.659, p = 0.001) than IBUS-SAS (r = 0.486, p < 0.001).

Conclusion

Intestinal ultrasound showed excellent concordance with enteroscopy for disease localization in the distal small bowel, supporting its use as a cost-effective, radiation-free, point-of-care modality. The addition of small intestinal contrast ultrasound (SICUS) significantly improved stricture detection. These findings support ultrasound-based strategies as first-line options for monitoring known Crohn’s disease, particularly in settings requiring repeated assessment or where access to cross-sectional imaging and device-assisted enteroscopy is limited.

References

1. Pal P, Mateen MA, Pooja K, et al. S1044 Correlation and Assessment of Small Bowel Lesions Using Cross-Sectional Imaging Techniques vs Small Intestinal Contrast UltraSonography in Known Crohn’s Disease (CACTUS-CD Trial): A Paired, Validating Study (NCT06125678). Official journal of the American College of Gastroenterology | ACG. 2024;119(10S):S731-S732. [10.14309/01.ajg.0001033544.90391.8a]
2. Na JE, Kim HS, Hong SN, et al. Comparison of an Endoscopic Scoring System and the Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn’s Disease. Gut and Liver. 2024;18(1):97-105.
3. Lu C, Rosentreter R, Parker CE, et al. International expert guidance for defining and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound: a consensus statement. Lancet Gastroenterol Hepatol. 2024;9(12):1101-1110.
4. Novak KL, Nylund K, Maaser C, et al. Expert Consensus on Optimal Acquisition and Development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: A Reliability and Inter-rater Variability Study on Intestinal Ultrasonography in Crohn's Disease. J Crohns Colitis. 2021;15(4):609-616.
5. Roseira J, Ventosa AR, de Sousa HT, Brito J. The new simplified MARIA score applies beyond clinical trials: A suitable clinical practice tool for Crohn's disease that parallels a simple endoscopic index and fecal calprotectin. United European Gastroenterol J. 2020;8(10):1208-1216.

Introduction

Steroid-refractory acute severe ulcerative colitis (SR-ASUC) is a life-threatening emergency that results in colectomy in approximately 40% of cases.¹ Several medical therapies have emerged as rescue treatments aimed at reducing the need for colectomy.^2-3However, direct comparative studies evaluating the relative efficacy of these therapies remain limited.⁴ This network meta-analysis aims to systematically review and compare the efficacy and safety of available rescue therapies for SR-ASUC, including biologics and small molecule treatments.

Aims & Methods

A systematic literature search was conducted using the MEDLINE, SCOPUS, and CENTRAL databases. Colectomy-free survival probabilities were extracted from Kaplan-Meier curves. A one-stage network meta-analysis using parametric Weibull regression was performed to estimate and compare the relative treatment effects of biologics and small molecule therapies. The primary outcome was colectomy-free survival at 4 and 12 weeks. This study was registered in PROSPERO (CRD420251030353).

Results

A total of 18 studies (5 randomized controlled trials and 13 cohort studies), including 1,706 patients with SR-ASUC, were included. Compared to placebo, standard-dose infliximab [hazard ratio (HR) 0.34, 95% CI: 0.20–0.60, p < 0.001], accelerated-dose infliximab [HR 0.38, 95% CI: 0.21–0.68, p = 0.001], and tofacitinib [HR 0.36, 95% CI: 0.19–0.69, p = 0.002] significantly improved colectomy-free survival. Cyclosporine also showed a trend toward reduced colectomy risk, though it did not reach statistical significance [HR 0.57, 95% CI: 0.31–1.01, p = 0.056]. There were no significant differences in overall adverse events or infection rates among the therapies. Based on SUCRA rankings, colectomy-free survival at both 4 and 12 weeks was highest for tofacitinib (SUCRA: 0.90 and 0.87), followed by accelerated-dose infliximab (0.95 and 0.85), standard-dose infliximab (0.87 and 0.83), and cyclosporine (0.81 and 0.74). (Figure 1 Colectomy free survival probability ; Kaplan-Meier curves)
Table 1. Pairwise table showing comparative efficacy in reducing colectomy risk of biologics and small molecule for SR-ASUC

Conclusion

Tofacitinib and accelerated-dose infliximab appear to be the most effective rescue therapies for improving colectomy-free survival in patients with SR-ASUC.

References

1. Dong C, Metzger M, Holsbø E, et al. Aliment Pharmacol Ther. 2020 Jan;51(1):8-33.
2. Honap S, Jairath V, Sands BE, et al. Gut. 2024 Sep 9;73(10):1763-1773.
3. Calméjane L, Laharie D, Kirchgesner J, et al. United European Gastroenterol J. 2023 Oct;11(8):722-732.
4. Choy MC, Seah D, Faleck DM, et al. Inflamm Bowel Dis. 2019 Jun 18;25(7):1169-1186.

Introduction

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex conditions characterized by significant clinical, immunological, molecular, genetic, and microbiological heterogeneity. Current therapeutic strategies, particularly biologics and Janus kinase (JAK) inhibitors, are effective for inducing clinical remission and controlling inflammation. However, one-third of patients fail to respond to these treatments, highlighting the need for predictive biomarkers to better tailor therapy and improve outcomes.

Aims & Methods

In this study, we conducted a multi-omic approach, integrating transcriptomics, proteomics, metabolomics, and metagenomics to identify biomarkers of treatment response in IBD. A cohort of 57 active CD and 70 active UC patients was analyzed before and after 14 weeks of treatment with anti-TNF, ustekinumab, vedolizumab, or tofacitinib. Response was evaluated using endoscopic criteria, categorizing patients as responders or non-responders. Biological samples [serum, urine, serum extracellular vesicles (EVs), intestinal biopsies, and stool] were analysed using RNA sequencing, liquid chromatography-mass spectrometry, nuclear magnetic resonance, and 16S rRNA gene sequencing to assess molecular and microbial profiles.

Results

Our results identified multiple mRNAs, proteins and metabolites associated with treatment response. Gene expression analysis in intestinal tissue showed significant differences between UC patients responders and non-responders to vedolizumab. Proteomic analysis of serum EVs and intestinal tissue samples revealed differentially expressed proteins between different study groups. Metabolomic analysis identified deregulation of 24 serum lipoproteins from CD responders to ustekinumab compared to non-responders. Pathway analysis highlighted significant enrichment in ketone and butyrate metabolism, mitochondrial electron transport chain activity, carnitine synthesis, and fatty acid oxidation pathways. Metagenomic analysis revealed microbial differences in UC patients responders to anti-TNF therapy compared to non-responders.

Conclusion

This multi-omics analysis uncovers promising biomarkers that could serve as predictive indicators of therapeutic response to biologics and JAK inhibitors. Nevertheless, further studies are crucial to confirm these findings and evaluate their clinical relevance in identifying patients most likely to respond to tailored therapeutic interventions. One of the challenges is integrating results from different omics approaches to create a more holistic understanding of the disease, potentially opening doors for more precise/early detection through multipanel biomarkers.

Introduction

Intestinal ultrasound (IUS) is increasingly used to objectively assess inflammatory bowel disease (IBD), yet a structured framework for evaluating operator proficiency is lacking. Structured objective assessment exists for general ultrasound(1), but not for IUS. The study aims to develop international consensus criteria for the objective structured assessment of IUS skills (OSAIUS) using a structured, multidisciplinary Delphi process.

Aims & Methods

IUS gastroenterology, radiology, internal medicine, and pediatric experts were identified worldwide. A modified Delphi process achieved expert consensus through multiple survey rounds. Four key OSAIUS domains were identified. In the first round, all experts rated the relevance of 20 predefined topics across these domains using a five-point Likert scale and were invited to propose additional topics. In the second round, participants re-rated 2 original topics and evaluated the newly suggested topics, each accompanied by standardized anchor text for the five Likert scores. A third round was conducted for final anchor text acceptance. Topic descriptions and anchor text wording were continuously revised to ensure clarity, accuracy, and terminology consistency throughout the process. We defined inclusion in the final assessment as ≥70% of experts rating a topic as 4 or 5 (relevant/essential).

Results

Of the 23 experts invited, 21 participated in the first round and 19 completed the second. Most respondents were gastroenterologists (n=15). In the first round, 18 topics were accepted. Two existing topics were marked for reassessment, along with four newly proposed topics for inclusion in subsequent rounds. In the second round, 3 topics were accepted: research segment documentation (mean score/rank 4.5/2.1), machine care/hygiene (4.4/3.6), post-resection anastomosis (4.4/2.8), totaling 21 final topics for the OSAIUS (Table 1). The topics discarded were examiner position (3.6/3.5), advanced machine settings (3.5/4.0), appendix (3.8/4.4), and transperianal ultrasound (2.8/6.1).

Conclusion

An international, multispecialty consensus defined the core technical competencies required to assess IUS proficiency. These findings establish the foundation for a globally accepted OSAIUS, which may support future certification at varying levels of expertise. The OSAIUS covers 4 domains, each with 5 topics, all individually rated from 1-5, giving a total score of 20-100. The proposed framework aims to reduce operator variability and offers a yet-to-be-validated tool for optimizing and objectively comparing educational interventions. Integrating expert-rated elements provides a robust basis for developing an internationally recognized IUS curriculum and standardized assessment protocol.

References

1) Tolgsaaard et al. International Multispecialty Consensus on How to Evaluate Ultrasound Competence: A Delphi Consensus Survey, PLoS One, 2013 Feb 28;8(2):e57687. doi: 10.1371/journal.pone.0057687

Disclosure

This study is supported by a grant from The Leona M. and Harry B. Helmsley Charitable Trust, as part of the IBUS eIUS Ed Project.
No author deaclears specifice conflicts of interest for this study

Introduction

Epithelial injury is a hallmark of chronic mucosal damage in Crohn’s disease (CD), which can lead to fibrostenotic strictures. Type VII collagen, a critical component of the epithelial basement membrane, forms U-shaped anchoring fibrils that link the basement membrane to the interstitial matrix by binding fibrillar collagen. Genetic mutations in the COL7A1 gene, which encodes type VII collagen, are known to impair fibril formation and reduce tissue tensile strength, resulting in epithelial dysfunction, as seen in disorders such as dystrophic epidermolysis bullosa. This highlights the essential structural role of type VII collagen in maintaining matrix stability. In CD, the importance of this protein is underscored by the presence of autoantibodies targeting type VII collagen in up to 50% of patients with CD. Loss of tissue integrity, because of loss of the interaction between the basement and interstitial matrix, leads to tissue dysfunction and fibrosis.

Aims & Methods

We investigated C7M, a biomarker of type VII collagen degradation, to assess its specificity for intestinal mucosal damage. We analyzed serum samples from CD patients enrolled in a prospective cohort study. The cohort included 62 CD patients undergoing surgical resection for fibrostenotic strictures and 49 patients with luminal disease receiving treatment adjustments without surgery. Serum was collected at baseline, post-operative day 1 (POD1), and one-month post-resection. C7M levels were quantified using a competitive ELISA.

Results

At baseline, C7M levels were significantly elevated in fibrostenotic CD patients (median: 9.79ng/mL) compared to those with luminal CD patients (median: 6.03ng/mL) (p<0.01, AUC: 0.69). In the resected group, C7M levels rose sharply on POD1 (p<0.0001, AUC: 0.81), suggesting acute release in response to surgical injury. By one-month post-surgery, C7M levels had returned to baseline, closely resembling those observed in luminal CD patients (p<0.0001, AUC: 0.80). C7M also demonstrated mild-moderate correlations to biochemical markers of inflammation, including CRP (rho=0.62, p<0.0001), hemoglobin (rho=-0.28, p=0.0024), thrombocytes (rho=0.24, p=0.0105), albumin (rho=-0.52, p<0.0001), and fecal calprotectin (rho=0.25, p=0.019).

Conclusion

C7M was elevated in fibrostenotic CD patients relative to luminal CD, indicating its potential as a biomarker of more severe or complex mucosal pathology. The pronounced but transient increase following surgery, with normalization within one month, further supports C7M as a dynamic marker of intestinal epithelial damage. These findings suggest C7M may serve as a novel, disease-specific biomarker for assessing mucosal integrity and inflammatory burden in CD.

Disclosure

Full time employee at Nordic Bioscience

Introduction

Mirikizumab (MIRI) is an anti-IL-23p19 antibody with demonstrated efficacy compared to placebo (PBO) in the treatment of moderately-to-severely active ulcerative colitis (UC) (LUCENT-1: NCT03518086; LUCENT-2: NCT03524092).¹ Prevention of IBD-related surgery and hospitalizations is a goal in disease-modification trials for preventing disease progression.² We described the rates of these events in the LUCENT-1 and -2 trials.

Aims & Methods

Patients were randomized to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for induction in LUCENT-1. Patients randomized to MIRI induction and achieving clinical response at Week (W)12 were re-randomized 2:1 in LUCENT-2 to subcutaneous MIRI 200 mg Q4W or PBO (MIRI withdrawal) for maintenance (W12-52). Descriptive statistics were used for proportion of patients in LUCENT-1 and -2 who had hospitalization and/or surgery by treatment group and the exposure-adjusted incident rate (IR). For LUCENT-1, hospitalizations in the induction period and surgeries during the induction and 16-week follow-up period were included. For LUCENT-2, all events were from the on-treatment period. Only hospitalizations associated with an adverse event with ≥24-hour stay (for any causes) were recorded.

Results

MIRI-treated patients had significantly lower IR of overall hospitalization, UC-related hospitalization, and overall surgery vs PBO-treated patients in LUCENT-1 (IR ratio MIRI vs PBO: 0.4, 0.1, 0.4, respectively). IR of UC-related surgery was 1.3 per 100 patient-years in MIRI-treated patients vs 2.6 per 100 patient-years in PBO group (Table). Mean time to first surgery or hospitalization from randomization was 30.5 days for PBO and 58.7 days for MIRI. Additional analyses revealed that patients on MIRI who had surgery/hospitalization in LUCENT-1 or -2 tended to have prior biologic failure and longer duration of disease. Similarly, in LUCENT-2, MIRI-treated patients had significantly lower IR of all-cause hospitalization and similar all-cause surgery vs PBO. No UC-related hospitalization and surgery were reported in the MIRI group while 2 UC-related hospitalizations (1.8 per 100 person-years) were reported from PBO.

Conclusion

Lower rates of UC-related hospitalizations and UC-related surgery were observed in patients treated with MIRI compared to those treated with PBO during the 12W induction LUCENT-1, and that impact continued through the 40W of maintenance LUCENT-2 with no UC-related hospitalizations or UC-related surgery reported in MIRI-treated patients.

References

1. D’Haens G, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. New England Journal of Medicine 2023;388(26):2444-2455.
2. Le Berre C, Peyrin-Biroulet L. Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD. Gastroenterology 2021;160(5):1452-1460.e21.

Disclosure

MR serves as a consultant and on advisory boards for AbbVie, Janssen, Bristol-Myers Squibb, UCB, Takeda, Pfizer, Prometheus Laboratories, Lilly, Celgene, and Amgen.
LPB has served as a consultant for AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; he received grants from Takeda, Fresenius Kabi, Celltrion; he served as a speaker for Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac; he also declares support travel by Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Gossamer Bio, Sandoz, MSD, Amgen, Lilly, Gilead, Thermo Fisher, Medac, CONNECT Biopharm; he declares stock options of Clinical trials Mobile Application.
JW, BZ, IR, KT, CO are employees and minor shareholders of Eli Lilly and Company.
SN has served on advisory board and speaker for Eli Lilly and Company, Pfizer and advisory board for madrigal and speaker for Janssen
TK has served as a paid consultant for Abbvie, Amgen, Biogen, Mundipharma, Hospira, Gilead, Janssen, Pfizer, MSD Sharp & Dome GmbH, and Novartis. He has received reimbursement of meeting participation fees and of travel and accommodation expenses from Abbvie, Janssen, MSD, and Takeda. He has received honoraria for preparing continuing medical education events from Abbvie, Falk, Janssen, MSD, Takeda, and Ferring Arzneimittel GmbH.
LM reports educational grants from Abbvie, Janssen, Pfizer and Takeda; advisory boards: AbbVie, Bristol Myers Squibb, Janssen, and Celltrion; consultant for Abbvie, Pfizer and Pharmacosmos.
FM has served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratorios Vitoria, Ferring, Hospira, and Biogen.