Reliability and Responsiveness of Endoscopic Indices for Assessing Crohn's Disease Postoperative Recurrence in the PREVENT trial.

Background And Aims: Assessing endoscopic activity is integral in the management of postoperative Crohn's disease (CD). We aimed to comprehensively characterize the reliability and responsiveness of different endoscopic instruments when used to assess postoperative CD activity.

Methods: Ileocolonoscopy videos (n=70) from the PREVENT trial were reviewed by three blinded central readers.

An exploratory single-cell analysis of peripheral blood mononuclear cells from vedolizumab-treated Crohn's disease patients identifies response-associated differences among the plasmacytoid dendritic cells and classical monocytes.

Background: Vedolizumab (VDZ) is a monoclonal antibody approved for the treatment of Crohn's disease (CD). Despite its efficacy, non-response to VDZ is common in clinical practice with no clear understanding of how it manifests. Here, we performed an exploratory study characterizing the cellular repertoire of responders and non-responders to VDZ during treatment.

Submucosal hyper-echogenicity on intestinal ultrasound is associated with fat deposition and predicts treatment non-response in patients with ulcerative colitis.

Background And Aims: The submucosa is the most responsive bowel wall layer on intestinal ultrasound (IUS) when assessing treatment response in ulcerative colitis (UC). Submucosal thickening with hyper-echogenicity is observed. This study aimed to quantify echogenicity and understand transmural changes in UC.

TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination.

Objectives: Tumour necrosis factor inhibitors (TNFi) are widely used and effective as treatment for immune-mediated inflammatory diseases (IMIDs). However, TNFi therapy causes a faster waning of antibody responses following vaccination. The underlying cause by which TNFi affect humoral immunity remains to be elucidated.

Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn's disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials.

Background: Despite the availability of biological therapies, suboptimal disease control remains a problem for patients with Crohn's disease. We report the results of the GALAXI-2 and GALAXI-3 studies, which aimed to assess the efficacy and safety of intravenous induction followed by subcutaneous maintenance therapy with guselkumab over 48 weeks in adults with moderately to severely active Crohn's disease.

Methods: GALAXI-2 and GALAXI-3 were identically designed, phase 3, randomised, double-blind, triple-dummy, treat-through trials with active and placebo comparators.

Development and External Validation of an Endoscopic and Histologic Pouchitis Assessment Tool: The Atlantic Pouchitis Index.

Background & Aims: No fully validated indices to measure pouchitis activity exist. We aimed to develop and externally validate a novel endoscopic and histologic index.

Methods: Endoscopists and pathologists used 11 (4 endoscopic, 4 histologic, 3 composite) existing indices and items from a prior Research and Development/University of California Los Angeles appropriateness exercise to assess pouchitis disease activity in videos and images from 98 patients with chronic antibiotic-refractory pouchitis who participated in a randomized placebo-controlled alicaforsen trial.

Development and validation of peripheral blood DNA methylation signatures to predict response to biological therapy in adults with Crohn's disease (EPIC-CD): an epigenome-wide association study.

Background: Biological therapeutics are widely used in Crohn's disease, with evidence of efficacy from randomised trials and real-world experience. Primary non-response is a common, poorly understood problem. We aimed to assess blood methylation as a predictor of response to adalimumab, vedolizumab, or ustekinumab in patients with Crohn's disease.

Point-of-care ultrasound provides useful information in children with Crohn's disease visiting the outpatient clinic.

Objectives: Point-of-care ultrasound (POCUS) is increasingly used in clinical practice. However, it's additional value next to conventional markers of disease activity has not been studied in paediatric Crohn's disease (CD). This study aimed to assess the clinical added value of POCUS in children with CD.

Development and validation of a novel Endoscopic ulcer Activity Score for Evaluation of Crohn's Disease (EASE-CD) using data from two randomised controlled trials.

Background: Endoscopy is essential for measuring luminal disease activity in Crohn's disease. Existing indices for evaluating endoscopic Crohn's disease activity are only modestly correlated with clinical disease activity, contain items with ambiguous definitions and poor interobserver reliability, and do not have validated thresholds for defining clinically relevant changes. To address these issues, we conducted a multiphase study to develop and validate a novel endoscopic index for Crohn's disease.

An International Consensus on Appropriate Management of Corticosteroids in Clinical Trials in Inflammatory Bowel Disease.

Background & Aims: Approval of new therapies for inflammatory bowel disease (IBD) requires rigorously designed and well-executed randomized controlled trials (RCTs). Corticosteroids remain a cornerstone of IBD induction therapy, and many patients in trials are enrolled while taking corticosteroids. Despite this, approaches to corticosteroid management in RCTs have been highly heterogeneous, often differing from clinical practice.

Immunogenicity and Efficacy of Subcutaneous Infliximab Monotherapy vs Combination Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Background & Aims: Intravenous (IV) infliximab (IFX) combined with an immunomodulator (combination therapy) outperforms IV IFX monotherapy in terms of clinical, endoscopic, and immunogenicity outcomes in patients with inflammatory bowel disease (IBD). With the advent of subcutaneous (SC) IFX, which is associated with higher serum drug concentrations, it is essential to assess whether SC IFX monotherapy provides similar pharmacokinetic and clinical benefits as combination therapy.

Methods: We conducted a systematic review and meta-analysis (until August 2024), of studies on patients with IBD treated with SC IFX.

Clinical Utility and Accuracy of Point-of-Care Testing for Anti-TNF Drug Monitoring and Loss of Response.

Background And Aims: Point-of-care tests (POCT) enable immediate measurement of anti-TNF blood concentrations. This study examined the association between loss of response (LOR) to infliximab (IFX) or adalimumab (ADL) and serum concentrations measured with POCT and enzyme-linked immunosorbent assay (ELISA) in inflammatory bowel disease (IBD) patients.

Methods: Patients with IBD with stored IFX or ADL serum samples were recruited.

Pharmacokinetic Comparability and Safety Between Original and Citrate-Free Mirikizumab Formulations for Subcutaneous Injections: Results from Three Clinical Trials.

Introduction: Mirikizumab, a p19-directed antibody against interleukin-23 (IL-23), is administered by subcutaneous (SC) injection. Injection site pain (ISP) associated with citrate buffers may negatively affect patient adherence to SC-administered treatments. We assessed the bioequivalence and safety of the citrate-free (CF) and original formulations of mirikizumab.

Potential predictors of efficacy outcomes following tofacitinib dose reduction in patients with ulcerative colitis in stable remission: a post hoc analysis of outcomes from the RIVETING study.

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC).

Objectives: To investigate potential predictors of efficacy in RIVETING.

Design: This post hoc analysis included patients with UC in stable remission (⩾6 months) on tofacitinib 10 mg twice daily (BID) maintenance therapy (⩾2 years of treatment), who received tofacitinib 5/10 mg BID in RIVETING.

Directionality of endoscopic and histologic healing in ulcerative colitis: a prospective pilot study.

Objective: Endoscopic and histologic healing in ulcerative colitis (UC) is hypothesized to progress proximally to distally, with healing of the distal rectosigmoid occurring last. However, this has not been empirically verified.

Methods: We performed a prospective cohort study in patients with pancolonic UC commencing treatment with a tumor necrosis factor (TNF) antagonist or vedolizumab.

Tofacitinib for the treatment of chronic pouchitis: A pilot study.

Background & Aims: Up to 15% of ulcerative colitis (UC) patients with an ileo-anal pouch will develop chronic or antibiotic refractory pouchitis. We aimed to evaluate the efficacy and safety of tofacitinib in these refractory patients.

Methods: In this prospective single center study, adult UC patients with chronic or antibiotic refractory pouchitis (pouchitis disease activity index [PDAI] ≥ 7) were treated with tofacitinib 10 mg twice daily for 8 weeks.

The impact of advanced medical therapies on time to resection and colorectal cancer outcomes in ulcerative colitis patients undergoing colectomy.

Background: We aimed to evaluate the impact of advanced medical therapies (biologicals and small molecules) on time to colectomy and oncological outcomes in ulcerative colitis (UC).

Methods: This cohort study included UC patients who underwent colectomy between 2003 and 2022 at 2 referral centers in Belgium and the Netherlands. Exposure was the use of advanced medical therapies.

Re-evaluating Methods for Assessing Differences in Response in Ileal vs Colonic Crohn's Disease: A Post-hoc Analysis of the FITZROY Trial.

Background And Aims: The ileum is the most commonly affected segment of the gastrointestinal tract in Crohn's disease [CD]. We aimed to determine whether disease location affects response to filgotinib, a Janus kinase [JAK] inhibitor, in patients with moderately-to-severely active Crohn's disease [CD] and applying appropriate methods to account for differences in measuring disease activity in the ileum compared with the colon.

Methods: This post-hoc analysis of data from the FITZROY phase 2 trial [NCT02048618] compared changes in the Crohn's Disease Activity Index [CDAI] and Simple Endoscopic Score for Crohn's Disease [SES-CD] among patients with ileal-dominant and isolated colonic CD treated with 10 weeks of filgotinib 200 mg daily or placebo.

Effect of mesenteric sparing or extended resection in primary ileocolic resection for Crohn's disease on postoperative endoscopic recurrence (SPICY): an international, randomised controlled trial.

Background: Retrospective research suggests that excision of the affected mesentery can improve outcomes after an ileocoecal resection in Crohn's disease. However, prospective data from randomised controlled trials are scarce. We aimed to compare rates of postoperative recurrence in patients with Crohn's disease who underwent extended mesenteric resection.