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Journal of Crohn's and Colitis Current Issue Correction to: Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER StudyMon, 19 May 2025 00:00:00 GMT by NIHR Oxford Biomedical Research Centre10.13039/501100013373Read more Correction to: Volume 18, Supplement 1Fri, 16 May 2025 00:00:00 GMT by This is a correction to Volume 18, Supplement 1, https://academic.oup.com/ecco-jcc/issue/18/Supplement_1Read more Correction to: Post-Discharge Outcomes of Elderly Patients Hospitalized for Inflammatory Bowel Disease Flare Complicated by Clostridioides difficile InfectionThu, 15 May 2025 00:00:00 GMT by This is a correction to: Idan Goren, Ortal Fallek Boldes, Tomer Boldes (et al), Post-Discharge Outcomes of Elderly Patients Hospitalized for Inflammatory Bowel Disease Flare Complicated by Clostridioides difficile Infection, Journal of Crohn’s and Colitis, 2024; https://doi.org/10.1093/ecco-jcc/jjae161Read more Be precise, be reproducible! The emerging role of artificial intelligence in inflammatory bowel disease endoscopyThu, 08 May 2025 00:00:00 GMT by Grading endoscopic disease activity is of pivotal importance in the management of patients with ulcerative colitis (UC) as patients achieving endoscopic healing have significantly more favorable clinical course, as exemplified by long-term steroid-free clinical remission and colectomy-free survival¹.Read more Early intestinal ultrasound response to biologic and small molecule therapy is accurate to predict treat-to-target endoscopic outcomes in children with ulcerative colitis: results from the prospective super sonic-UC studyFri, 02 May 2025 00:00:00 GMT by Read more Expert recommendations to standardize transcriptomic analysis in inflammatory bowel disease clinical trialsTue, 29 Apr 2025 00:00:00 GMT by

Abstract

Background and aims

Substantial methodological and reporting heterogeneity confounds the interpretation and generalizability of transcriptomic data for inflammatory bowel disease (IBD) studies. We aimed to develop recommendations to standardize transcriptomic research in clinical trials.

Methods

A 2-part study was undertaken. A systematic review identified reports of transcriptomic analyses utilizing samples from IBD clinical trials. Studies that used global RNA assay platforms were included. Data regarding study design, methodological approaches, and reporting of transcriptomic research were extracted. The systematic review results informed a modified Research and Development/University of California Los Angeles appropriateness methodology process and the development of survey statements focused on topics with substantial methodological heterogeneity. A panel of 16 IBD translational researchers and gastroenterologists rated the appropriateness of survey statements in 2 rounds.

Results

The systematic review identified 37 reports that included transcriptomic analyses of samples from IBD patients. The appropriateness of 416 statements was rated by 15 panellists in the first survey. The final survey included 305 statements, of which 14 panellists rated 75% appropriate, 1% inappropriate, and 24% uncertain. The panel determined that transcriptomic analysis for multiple research objectives was appropriate at most phases of clinical development in patients with active disease. Recommendations regarding study sample size; biopsy number, location, preservation, and storage; and data analysis and reporting were also generated.

Conclusion

The persistence of existing methodologic heterogeneity may continue to limit the value of transcriptomic research in IBD. This study provides expert recommendations to address and overcome these discrepancies and foster the inclusion of this research in clinical development.Read more Endoscopic submucosal dissection for visible dysplasia in inflammatory bowel disease: a nationwide multicenter cohort from the GETAID and the SFEDFri, 25 Apr 2025 00:00:00 GMT by Read more A multicenter study of the real-world effectiveness and safety of risankizumab in Crohn’s diseaseThu, 24 Apr 2025 00:00:00 GMT by Read more 5-Aminosalicylates for non-surgical patients with active or quiescent Crohn’s disease: an overview of systematic reviews (umbrella review)Mon, 21 Apr 2025 00:00:00 GMT by Read more Triple biologic therapy for refractory Crohn’s diseaseSat, 19 Apr 2025 00:00:00 GMT by

Abstract

Background

Despite significant advances in the therapeutic management of Crohn’s disease (CD), a subset of patients remains refractory to available treatments. Dual-targeted therapy (DTT), combining biologics or biologics with small molecules, has emerged as a promising approach. While evidence supporting DTT continues to grow, reports of patients treated with a combination of 3 biologic or targeted agents remain exceptionally rare.

Case Presentation

We report the case of a 30-year-old male with a complex clinical course, initially diagnosed with ulcerative colitis and later reclassified as CD following ileal pouch-anal anastomosis, due to subsequent small bowel and perianal involvement. The patient also had concomitant ankylosing spondylitis. Despite multiple lines of therapy, including, anti-tumor necrosis factor agents, vedolizumab, ustekinumab, and upadacitinib, both CD and ankylosing spondylitis remained clinically active. In the absence of alternative therapeutic options and continued refusal of surgery, a triple combination of certolizumab pegol, ustekinumab, and vedolizumab was initiated and maintained over 10 months. While the treatment was well tolerated and ankylosing spondylitis remained in remission, no impact was observed on CD.

Discussion

This case highlights the challenges of managing refractory inflammatory bowel disease with overlapping immune-mediated conditions. Although the combination of biologics targeting distinct inflammatory pathways is conceptually appealing and supported by emerging data on DTT, the effectiveness of triple therapy remains uncertain in some patients.

Conclusions

Triple biologic therapy remains experimental and should be approached with caution, pending more robust evidence. Larger and translational studies are needed to better identify patients who may benefit, define optimal combinations, and clarify long-term safety of these combinations.Read more Anti-integrin αvβ6 IgG antibody as a diagnostic and prognostic marker in ulcerative colitis: A cross-sectional and longitudinal study defining a specific disease phenotypeSat, 19 Apr 2025 00:00:00 GMT by Read more Biglycan deficiency alleviates intestinal fibrosis through BMP-7-mediated Smad1/5/8 signalingFri, 18 Apr 2025 00:00:00 GMT by Read more Drug tissue concentration and STAT3 modulation as determinants of tofacitinib response in ulcerative colitisThu, 17 Apr 2025 00:00:00 GMT by

Abstract

Introduction

Inflammatory bowel disease management has advanced with therapies like Janus kinase inhibitors (JAKi). Despite their promise, JAKi pharmacokinetic-pharmacodynamic (PK-PD) profiles and tissue-level effects remain underexplored. This study investigates tissue and serum tofacitinib levels, their correlation with therapeutic efficacy, and molecular mechanisms underlying treatment response.

Methods

Thirty refractory ulcerative colitis (UC) patients receiving tofacitinib were prospectively studied. Tissue biopsies and serum samples were collected pre- and post-induction for PK analysis using liquid chromatography mass spectrometry. RNA sequencing and cytokine profiling were performed on tissue samples to explore molecular responses. Endoscopic improvement was defined as a Mayo endoscopic subscore of 0-1 by week 16.

Results

Tofacitinib tissue concentrations were 25-fold higher than serum levels and significantly correlated (ρ=0.92, P < .001). Responders showed significantly higher tissue drug exposure (1047.5 ng/g vs 467.1 ng/g, P = .02) at the time of endoscopic assessment. Tofacitinib treatment reduced phosphorylated STAT3 (pSTAT3) levels, particularly in responders (P = .02). RNA sequencing revealed gene modules linked to tissue drug and pSTAT3 concentrations. Gene set enrichment analysis showed that these were more frequent in non-responders and associated with JAK-STAT pathways.

Conclusions

This study underscores the importance of tissue tofacitinib levels in UC treatment efficacy, with pSTAT3 reduction serving as a potential marker of drug efficacy. RNA sequencing identified molecular pathways for potential biomarkers and novel therapeutic targets in tofacitinib non-responders.Read more Effectiveness and safety of rectal tacrolimus in patients with ulcerative colitis. TACRO-TOPIC study of GETECCUThu, 10 Apr 2025 00:00:00 GMT by Read more Association of bile acid diarrhea with symptoms and disease activity in Crohn’s disease: post-hoc clinical trial analysis of serum 7a-hydroxy-4cholestern-3-one, C4, in patients with active Crohn’s diseaseWed, 09 Apr 2025 00:00:00 GMT by Read more The mediating role of psychological inflexibility on internalized stigma and patient outcomes in a sample of adults with inflammatory bowel diseaseTue, 01 Apr 2025 00:00:00 GMT by

Abstract

Background

This study examined the relationship between psychological inflexibility, internalized stigma, and patient outcomes in adults with inflammatory bowel disease (IBD). It aimed to explore if psychological inflexibility mediated the relationship between internalized stigma and patient outcomes.

Methods

Three hundred and eighty-two participants with IBD took part in a cross-sectional quantitative study conducted via an online survey from May to December 2020. Participants completed questionnaires that assessed psychological inflexibility, committed action, internalized stigma related to IBD, psychological distress, IBD self-efficacy, self-concealment, beliefs about emotions, and fatigue. Participants also completed a sociodemographic and clinical questionnaire in addition to a bespoke Covid-19 questionnaire. Pearson’s correlations and exploratory simple mediation analyses were used to examine relationships between variables and the mediating effect of psychological inflexibility.

Results

40.5% of participants experienced internalized stigma. Higher psychological inflexibility was associated with higher internalized stigma, lower committed action, poorer health-related quality of life, lower IBD self-efficacy, higher self-concealment, higher fatigue, and more negative beliefs about emotions. Psychological inflexibility partially mediated the relationship between internalized stigma and several patient outcomes (psychological distress, IBD health-related quality of life, IBD self-efficacy, and self-concealment) and completely mediated the relationship between internalized stigma and fatigue.

Conclusion

Psychological inflexibility significantly impacts the quality of life in individuals with internalized stigma related to IBD and mediates the relationship between internalized stigma and patient outcomes. Increasing psychological flexibility in adults with IBD may reduce distress and enhance quality of life. Longitudinal studies and trials of psychological interventions targeting psychological flexibility warrant exploration.Read more Fidaxomicin for Clostridioides difficile infection in patients with inflammatory bowel disease: a multicenter retrospective cohort studyTue, 01 Apr 2025 00:00:00 GMT by

Abstract

Background and aims

Inflammatory bowel disease (IBD) patients with Clostridioides difficile infection (CDI) are at increased risk of adverse outcomes. Data on fidaxomicin use in IBD remain scarce. We assessed the effectiveness and safety of fidaxomicin for CDI and its impact on IBD outcomes in a large international cohort.

Methods

Adult patients with ulcerative colitis (UC) or Crohn’s disease (CD) treated with fidaxomicin for documented CDI were retrospectively included. The primary outcome was CDI recurrence rate within 8 weeks (C. difficile toxin detection and CDI-targeted therapy). Secondary outcomes included sustained response (no CDI-targeted therapy within 12 weeks), IBD therapy escalation, colectomy rate, and all-cause mortality within 30, 90, and 180 days.

Results

Ninety-six patients (57 UC and 39 CD) from 20 IBD centers were included. Most were on advanced IBD therapy. Half had a previous CDI episode, 15% a severe episode. CDI recurrence rate was 10% at week 8, and sustained response 82% at week 12. Compared with patients with previous CDI episode, patients at first episode tended to have a lower recurrence (4.3% vs 16%; P = .06) and higher sustained response (91% vs 75%; P = .04) rate. IBD therapy escalation was required in 48% with a numerically lower need for patients achieving vs not-achieving sustained response within 30 days (12% vs 20%; P = .42). Five UC patients underwent colectomy. One death unrelated to CDI or IBD occurred. One moderate and 5 mild adverse events were reported.

Conclusions

Fidaxomicin was effective and safe in IBD patients with CDI, with greater effectiveness in CDI-naïve patients, potentially influencing short-term IBD outcomes.Read more Real-world effectiveness of ustekinumab versus anti-TNF or vedolizumab in ulcerative colitis: induction and 12-month maintenance results from the prospective, observational RUN-UC studyThu, 27 Mar 2025 00:00:00 GMT by

Abstract

Background

Real-world evidence studies of ustekinumab (UST) in ulcerative colitis (UC) are needed because randomized controlled trials do not represent unselected patient populations in everyday clinical practice. Patients with UC were recruited when starting biologic therapy for the first time or switching to a new biologic therapy. This study assessed the effectiveness of maintenance therapy with UST in comparison to anti-TNF or vedolizumab (VDZ) at 12 months.

Methods

Between 2020 and 2022, 507 UC patients starting biologic therapy for the first time or switching to a new biologic therapy were enrolled at 34 inflammatory bowel disease (IBD)-specialized centers in Germany. After excluding patients receiving other biologics or small molecules, as well as those with stomas or missing outcomes, the final sample consisted of 476 patients. The outcomes were clinical response, clinical remission (CR), and steroid-free remission. Propensity score (PS) adjustment with inverse probability of treatment weighting was used to reduce the effect of confounding due to physician selection of therapy.

Results

A total of 476 patients with UC were included in the analysis (UST: 147, anti-TNF: 168, VDZ: 161). Treatment persistence over 12 months differed significantly (P < .001) between UST (93.9%), VDZ (87.0%), and anti-TNF (75.0%). The PS-weighted effectiveness of UST in the mITT analysis at month 12 was not significantly different from anti-TNF or VDZ (CR: UST 26.9%, anti-TNF 34.7%, VDZ 40.9%; P = .063).

Conclusions

In the prospective RUN-UC study with PS-weighted groups, UST showed higher treatment persistence but no significant difference in maintenance effectiveness compared to anti-TNF or VDZ in UC.Read more The use of International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in patients with ulcerative colitis: applicability and comparison with other ultrasound scoresMon, 24 Mar 2025 00:00:00 GMT by

Abstract

Background and aims

The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) is an intestinal ultrasound (IUS) score validated for Crohn’s disease, potentially applicable to ulcerative colitis (UC). We aimed to confirm the applicability of IBUS-SAS to UC, while comparing its performance with other IUS scores.

Methods

Adult patients with UC undergoing colonoscopy were prospectively included and scored with both the Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Intestinal ultrasound was performed within 4 weeks of endoscopy, measuring IBUS-SAS and other 5 UC-developed IUS scores. The Spearman’s rank coefficient (ρ) was used to perform correlations, while receiver operating characteristic curves were compared with the Hanley & McNeil method.

Results

In total, 185 patients were included. The IBUS-SAS showed a strong correlation with both the MES (ρ = .72, P < .01) and the UCEIS (ρ = .73, P < .01). Its area under the curve to detect an endoscopic activity of at least moderate severity (MES ≥ 2 and UCEIS ≥ 5) was 0.87 and 0.89, respectively. The optimal cutoffs of IBUS-SAS to detect a MES ≥ 2 and an UCEIS ≥ 5 were > 19 (sensitivity 79%, specificity 84%) and > 23 (sensitivity 88%, specificity 75%), respectively. Consistently, all the investigated IUS scores correlated with both the MES and the UCEIS (P < .01).

Conclusions

The IBUS-SAS has an optimal performance in the assessment of UC endoscopic activity, despite having been initially developed for CD. Therefore, it might be adopted as a reference score both for CD and UC activity.Read more Characterization of Inflammatory Bowel Disease Heterogeneity Using Serum Proteomics: A Multicenter StudyMon, 04 Nov 2024 00:00:00 GMT by

Abstract

Background

Recent genetic and transcriptomic data highlight the need for improved molecular characterization of inflammatory bowel disease (IBD). Proteomics may advance the delineation of IBD phenotypes since it accounts for post-transcriptional modifications.

Aims

We aimed to assess the IBD spectrum based on inflammatory serum proteins and identify discriminative patterns of underlying biological subtypes across multiple European cohorts.

Methods

Using proximity extension methodology, we measured 86 inflammation-related serum proteins in 1551 IBD patients and 312 healthy controls (HC). We screened for proteins exhibiting significantly different levels among IBD subtypes and between IBD and HC. Classification models for differentiating between Crohn’s disease (CD) and ulcerative colitis (UC) were employed to explore the IBD spectrum based on estimated probability scores.

Results

Levels of multiple proteins, such as interleukin-17A, matrix metalloproteinase-10, and fibroblast growth factor-19, differed (fold-change >1.2; false discovery rate <0.05) between ileal versus colonic IBD. Using multivariable models, a protein signature reflecting the IBD spectrum was identified, positioning colonic CD between UC and ileal CD, which were at opposite ends of the spectrum. Based on area under the curve (AUC) estimates, classification models more accurately differentiated UC from ileal CD (median AUCs > 0.73) than colonic CD (median AUCs < 0.62). Models differentiating colonic CD from ileal CD demonstrated intermediate performance (median AUCs: 0.67–0.69).

Conclusions

Our findings in serum proteins support the presence of a continuous IBD spectrum rather than a clear separation of CD and UC. Within the spectrum, disease location may reflect a more similar disease than CD versus UC, as colonic CD resembled UC more closely than ileal CD.Read more Post-Discharge Outcomes of Elderly Patients Hospitalized for Inflammatory Bowel Disease Flare Complicated by Clostridioides difficile InfectionMon, 21 Oct 2024 00:00:00 GMT by Read more