Unravelling the genetic architecture of inflammatory bowel disease multiplex families with rare and common variant polygenic risk scores.

Background And Aims: Inflammatory bowel disease (IBD) often affects multiple relatives, pointing towards shared genetic and/or environmental factors. This study evaluates the importance of known IBD risk variants, and of genetic determinants of smoking in such multiplex families.

Methods: We studied 65 IBD multiplex families, comprising 146 Crohn's disease [CD], 33 ulcerative colitis [UC], and 111 unaffected relatives.

Optimizing the switch from escalated intravenous to subcutaneous infliximab: a population pharmacokinetics-pharmacodynamics study.

Background And Aims: It remains unclear if patients on escalated intravenous (IV) infliximab can switch to standard subcutaneous (SC) infliximab CT-P13 of 120 mg bi-weekly (Q2W) injections without losing therapeutic response. This study investigates the dose-exposure-response relationship during the IV-to-SC switching of infliximab in Crohn's disease (CD) and ulcerative colitis (UC).

Methods: Data were collected from healthy volunteers and patients with CD and UC in different Phase I studies.

Environmental and Inflammatory Factors Drive Perinuclear-Antineutrophil Cytoplasmic Antibodies (pANCA) in Ulcerative Colitis: A European Twin Study.

Background: Perinuclear-antineutrophil cytoplasmic antibodies (pANCA) have been identified in familial ulcerative colitis (UC), but the mechanism underlying their expression remains elusive. We assessed the role of genetic predisposition, environmental factors and systemic subclinical inflammation in the development of pANCA in a twin cohort with UC.

Methods: A total of 48 twin pairs (Leuven, Belgium n = 4, Maastricht, The Netherlands n = 6 and Örebro, Sweden n = 38) with UC were included.

Effect of five dietary emulsifiers on inflammation, permeability, and the gut microbiome: a placebo-controlled randomized trial.

Background And Aims: Dietary emulsifier consumption might promote intestinal inflammation, eventually leading to inflammatory bowel diseases. However human data are scarce and involve a limited number of emulsifiers. We studied the effects of an emulsifier-free diet (EFD) and specific emulsifier supplementation.

Comparison of the FDA and EMA guidance on drug development in ulcerative colitis: an expert panel review.

Background And Aims: The Food and Drug Administration (FDA) and European Medicines Agency (EMA) ensure the safety, efficacy, and security of treatments, including therapies for immune-mediated disorders such as inflammatory bowel disease (IBD). Their clinical trial guidelines aid sponsors in designing robust studies. While the EMA updated its guidelines for ulcerative colitis (UC) in 2018, the FDA issued new recommendations in April 2022.

Assessment of PredictSURE IBD Assay in a Multinational Cohort of Patients With Inflammatory Bowel Disease.

Background And Aims: PredictSURE IBD is a prognostic blood test that classifies newly diagnosed, treatment-naïve Inflammatory Bowel Disease (IBD) patients into 'IBDhi' (high-risk) or 'IBDlo' (low-risk) groups (risk of future aggressive disease). We evaluated this assay in a multinational cohort and explored the effect of concomitant corticosteroids on its discrimination.

Methods: One hundred thirty-six (71 Ulcerative colitis [UC], 65 Crohn's Disease [CD]) and 41 (15 UC, 26 CD) patients with active IBD were 'unexposed' and 'exposed', respectively, to corticosteroids at baseline blood sampling.

Unraveling Genetic Versus Environmental Factors Determining Disease Course in Inflammatory Bowel Diseases: A Population-Based Cohort Study in First- and Second-Generation Immigrants.

Background: Inflammatory bowel diseases (IBD) incidence in immigrants approximates that of the host country in progressive generations but less is known about their disease outcome. We investigate how the immigrant generation affects IBD outcomes.

Methods: In this population-based cohort study, the risks of first IBD-related hospitalization, first IBD-related surgery, need for advanced therapies, and perianal disease were compared between first- and second-generation immigrants (stratified into Western/non-Western) and native Danes, using Cox proportional hazard regression to estimate adjusted hazard ratios (aHRs), correcting for sex, age at IBD diagnosis, and calendar year of IBD diagnosis.

Dietary convergence induces individual responses in faecal microbiome composition.

Background: Dietary variation has been identified as a key contributor to microbiome diversification. However, assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodological hurdles. We aimed to estimate the impact of a reduction of dietary variation (dietary convergence) on faecal microbiota composition among individuals consuming a Western-type diet.

Obefazimod in patients with moderate-to-severely active ulcerative colitis: efficacy and safety analysis from the 96-week open-label maintenance phase 2b study.

Background And Aims: Obefazimod is an oral small molecule that selectively enhances the expression of a single micro-RNA (miRNA), miR-124. Obefazimod has demonstrated safety and efficacy in patients with moderate-to-severely active ulcerative colitis (UC) in a phase 2b induction trial. This analysis presents the 2-year outcome data of the open-label maintenance (OLM) study.

Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses.

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients.

Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study.

Background: The U-ACTIVATE long-term extension study aims to evaluate the long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis. Here, we report interim results after 3 years of total treatment.

Methods: U-ACTIVATE is an ongoing, 288-week, phase 3, long-term extension study done at 307 centres across 43 countries (active sites on Dec 31, 2021, are presented as part of this interim analysis) and began on Jan 31, 2017.

Differential effects of tofacitinib on macrophage activation contribute to lack of response in ulcerative colitis patients.

Background And Aims: Tofacitinib, a Janus kinase inhibitor, is approved for the treatment of moderate-to-severe ulcerative colitis. Nonetheless, 40-60% of patients will not respond adequately. The mechanisms underlying responses to tofacitinib remain unknown.

The Development of a Multidisciplinary Care Pathway for Patients with Inflammatory Bowel Disease Before, During and After Pregnancy.

: Recent advancements have significantly enhanced our understanding of the interplay between inflammatory bowel disease (IBD) and reproductive health. While international organizations provide guidelines for best practices, translating them into actionable strategies is crucial. This study aimed to develop a comprehensive care pathway to enhance preconception counselling and support for patients with IBD in the perinatal period, ensuring they receive optimal expert care.

Cooking methods affect advanced glycation end products and lipid profiles: A randomized cross-over study in healthy subjects.

Thermal treatments used in ultra-processed foods (UPFs) lead to advanced glycation end products (AGEs). UPFs and serum AGEs are associated with cardiometabolic disease. We explore differential cooking methods as a mechanistic link between UPFs and detrimental health outcomes through a randomized cross-over cooking method trial in healthy subjects using identical ingredients and a deep profiling analysis.

Efficacy and Safety of Mirikizumab in the Treatment of Moderately to Severely Active Ulcerative Colitis Regardless of Baseline Modified Mayo Score: Results From the Phase 3 LUCENT Trials.

Background: The modified Mayo score (mMS) is a measure for ulcerative colitis (UC) disease activity. Recent US Food and Drug Administration guidance for moderately to severely active UC trials suggests that patients should have baseline mMS of 5-9 including an endoscopy score of at least 2, as opposed to the previous range of 4-9. This disclosure reports results from patients with UC with baseline mMS of 5-9 who received mirikizumab, a monoclonal antibody directed against the interleukin-23 p19 subunit, or placebo in the phase 3 LUCENT trials.

Drug tissue concentration and STAT3 modulation as determinants of tofacitinib response in ulcerative colitis.

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.

Serum extracellular RNAs as a noninvasive approach to differentiate inflammatory bowel disease subtypes: a proof-of-concept study.

Background And Aims: Extracellular RNAs (exRNAs), including in serum, show potential as noninvasive biomarkers. However, their (patho)physiological role is still not fully understood. In this study, we characterized serum exRNAs in patients with inflammatory bowel diseases (IBDs) and evaluated their ability to differentiate ulcerative colitis (UC) from Crohn's disease (CD).

Mirikizumab Improves Quality of Life and Work Productivity in Patients with Moderately to Severely Active Crohn's Disease: Results from the Phase 3 VIVID-1 Study.

Introduction: Mirikizumab demonstrated significant efficacy compared with placebo in patients with Crohn's disease (CD) in the phase 3 VIVID-1 study. In this study, we report the impact of mirikizumab vs placebo on health-related quality of life (HRQoL) and work productivity in VIVID-1.

Methods: VIVID-1 patients randomized to receive mirikizumab (N = 579), or placebo (N = 199) were included.

Real-time automated assessment of histological disease activity in patients with ulcerative colitis using single-wavelength endoscopy technology.

Single-wavelength endoscopy (SWE) has shown promising results in assessing histological disease activity in ulcerative colitis. Our objective was to validate the real-time performance of a bedside prototype of SWE computer-aided diagnosis (CAD) as proof of concept.A bedside module for real-time use evaluated histological disease activity when endoscopy was performed in the rectum and sigmoid based on white-light endoscopy and SWE (410 nm monochromatic light).

Efficacy and Safety of Etrasimod in Patients With Moderately to Severely Active Ulcerative Colitis Stratified by Baseline Modified Mayo Score: A Post Hoc Analysis From the Phase 3 ELEVATE UC Clinical Program.

Background: Etrasimod is an oral, once daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). This post hoc analysis of the ELEVATE UC clinical program describes etrasimod efficacy and safety by patients' baseline disease activity.

Methods: Predefined efficacy endpoints were assessed at week 12 in patients with moderately (modified Mayo score [MMS] 5-7) or severely (MMS 8-9) active UC using pooled data from ELEVATE UC 52 and ELEVATE UC 12.

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.

No Increased Risk of Venous Thromboembolism or Infectious Complications after Janus Kinase Inhibitor Exposure in Patients with Ulcerative Colitis Undergoing Surgery.

Introduction: Total colectomy for ulcerative colitis (UC) is associated with postoperative morbidity, including venous thromboembolic events (VTE). In light of recent concerns about increased major adverse events associated with Janus kinase (JAK) inhibitor exposure, we aimed to evaluate the postoperative VTE risk as well as other complications in UC patients undergoing colectomy.

Methods: This single-center retrospective cohort study included all UC patients who underwent (procto)colectomy between 2013 and March 2022 and documented the 180-day postoperative non-infectious and infectious complications.

Ustekinumab Drug Clearance Is Better Associated with Disease Control than Serum Trough Concentrations in a Prospective Cohort of Inflammatory Bowel Disease.

: This study aimed to compare the association of ustekinumab (UST) drug clearance (CL) and trough drug concentrations with disease activity in patients with inflammatory bowel diseases (IBDs). : A prospective cohort of 83 patients with IBD receiving maintenance therapy with 90 mg subcutaneous UST was analyzed using Bayesian PK modeling. UST concentrations and antibodies to UST (ATU) were collected at the trough and measured using a drug-tolerant homogenous mobility shift assay (HMSA).

A transcriptomic score to classify the inflammation-dysplasia-cancer sequence lesions in inflammatory bowel disease.

Background And Aims: Inflammatory bowel disease (IBD) is associated with a higher risk of developing colorectal cancer, according to the inflammation-dysplasia-cancer (IDC) sequence from inflammation to colitis-associated colorectal cancer (CAC). The objective of this study was to identify and generate a transcriptomic signature and score, related to the IDC sequence, that could ultimately classify dysplasia and cancer in IBD.

Methods: Demographics, clinical parameters, histological characteristics, and RNA-sequencing data were evaluated on 134 formalin-fixed paraffin-embedded lesions from 2 independent cohorts of IBD patients with low- or high-grade dysplasia (LGD, HGD) and/or CAC.