Influence of Pharmacokinetic-Pharmacodynamic Failure Mechanisms on Outcomes in Biologic Therapy Sequencing in Inflammatory Bowel Disease: A Retrospective Cohort Study.

Background: Increasing therapeutic options for inflammatory bowel disease calls for tools to aid choice of sequencing. We investigated if pharmacokinetic (PK) and pharmacodynamic (PD) failure mechanisms prompting therapy change influenced subsequent outcomes when switching to a different biologic drug class.

Methods: Retrospective single-center cohort study including patients treated first with tumor necrosis factor (TNF) inhibitors, followed by vedolizumab, and then ustekinumab.

Postoperative Outcomes in Tofacitinib-Treated Patients With Acute Severe Ulcerative Colitis Undergoing Colectomy.

Background And Aims: Up to 30% of patients with acute severe ulcerative colitis (ASUC) will require urgent colectomy despite initiation of intravenous corticosteroids and rescue therapies. Janus kinase inhibitors, such as tofacitinib, have emerged as an effective agent for ASUC; however, there are currently limited data evaluating the risk of postoperative complications among patients who received tofacitinib treatment for an episode of ASUC compared with infliximab.

Methods: We conducted a multicenter, retrospective, case-control study of patients hospitalized with ASUC who underwent colectomy, comparing patients treated with tofacitinib prior to colectomy with infliximab-treated controls.

Inflamed Intestinal Epithelial Cells From Patients With Ulcerative Colitis Restore a Noninflamed Transcriptional Profile Upon In Vitro Expansion.

Ulcerative colitis (UC) is characterized by chronic relapsing inflammation starting from the rectum and distal colon, which in severe disease cases may affect the entire colon. Intestinal stem cells (ISCs) directly isolated from inflamed UC colonic tissue specimens have been found to present an inflammatory gene expression profile. However, a critical issue is whether these cells retain memory of exposure to inflammation and/or therapeutics.

A Novel Case of Biallelic MLH3 Variants in a Patient With Rectal Cancer and Polyps.

An increasing number of autosomal recessive forms of adenomatous polyposis have been described, but some in very few cases. Here, we describe a rare case of biallelic germline pathogenic variants in the MLH3 gene, implicating it as a potential cause of early colorectal cancer. The patient, a 47-year-old woman, presented with rectal bleeding, leading to the discovery of a malignant rectal tumor and adenomas during colonoscopy.

Risk-based pricing models and the role they might play in patients' access to new stem cell therapies.

Stem cell research is currently undergoing a promising transformation from primarily basic research to increasing emphasis on translation and clinical trials. To reach patients, however, stem cell treatments need to be not only technically but also economically viable. In this commentry we present insights into emerging pricing models that may help ensure access to advanced and expensive treatments like stem cell therapies.

Protocol for scoping review: Patient-controlled sedation.

Background: In settings where general anaesthesia is unnecessary, effective sedation, analgesia and local anaesthesia are crucial for optimal outcomes. Traditionally, sedation have been managed and controlled by healthcare professionals, but advancements in pharmacology and technology have renewed the way we are able to sedate. Patient-controlled sedation (PCS) offers a promising approach, allowing patients to adjust their sedation levels during procedures.

Therapeutic drug monitoring of vedolizumab therapy in inflammatory bowel disease.

Background: Therapeutic drug monitoring is effective for optimizing anti-tumor necrosis factor therapies in inflammatory bowel disease, but for vedolizumab, a gut-selective leucocyte migration inhibitor, data are scarce.

Methods: Observational cohort study including 116 bio-experienced inflammatory bowel disease patients treated with vedolizumab for active luminal disease. Biobanked trough blood samples (n = 676) covering 96% of patients were analyzed using a drug-binding immunofluorometric assay.

Immune cell-derived signals governing epithelial phenotypes in homeostasis and inflammation.

The intestinal epithelium fulfills important physiological functions and forms a physical barrier to the intestinal lumen. Barrier function is regulated by several pathways, and its impairment contributes to the pathogenesis of inflammatory bowel disease (IBD), a chronic inflammatory condition affecting more than seven million people worldwide. Current treatment options specifically target inflammatory mediators and have led to improvement of clinical outcomes; however, a significant proportion of patients experience treatment failure.

Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn's Disease Might Be Associated With Increased Rates of Stoma Construction.

Background: Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn's disease (CD) with radiologically guided percutaneous drainage (PD) was debated.

Methods: This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers.

Results: Seventeen patients (4.

Adult-Onset Autoimmune Enteropathy: A Case Report.

Small bowel villous atrophy is most often caused by celiac disease in the Western world, but other diseases should be explored in patients without positive serology. Adult-onset autoimmune enteropathy (AIE) is a rare cause of villous atrophy first known in children with T-cell dysregulation but also seen in adults with autoimmune predispositions. Here, an 82-year-old woman with autoimmune thyroiditis was admitted with weight loss and watery diarrhoea not responding to diet change.

Trajectories of health-related quality of life and fatigue during vedolizumab therapy in inflammatory bowel disease.

Background And Aim: Normalizing health-related quality of life (QoL) and fatigue are important long-term treatment targets in inflammatory bowel disease (IBD). We examined their evolution in relation to changes in disease activity during vedolizumab therapy.

Methods: Cohort study of biologically refractory IBD patients treated with vedolizumab.

Identifying and understanding disease burden in patients with inflammatory bowel disease.

Objective: Physicians tend to focus on biomedical targets while little is known about issues important to patients. We aimed to identify critical concepts impacting patients with inflammatory bowel disease (IBD).

Design: We performed a survey of patients with IBD in biologic therapy (n=172) and used a validated qualitative method called group concept mapping (GCM) in patient workshops.

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review.

Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome.

Therapeutic drug monitoring in inflammatory bowel disease: implementation, utilization, and barriers in clinical practice in Scandinavia.

Background And Aims: Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia.

Methods: A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies.

Discontinuation of Infliximab Therapy in Patients with Crohn's Disease.

BACKGROUND: Whether infliximab therapy can be successfully discontinued after patients with Crohn’s disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn’s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks.

Fatigue is a systemic extraintestinal disease manifestation largely independent of disease activity, chronicity, and nutritional deficiencies in inflammatory bowel disease on biologics.

Background: Fatigue is a common symptom reported by patients with chronic immunoinflammatory diseases and with profound negative implications on health-related quality of life. This study aimed to delineate underlying components contributing to fatigue in patients with inflammatory bowel disease (IBD) receiving biologic therapy.

Methods: Cross-sectional questionnaire study of all patients with IBD receiving any biologic therapy at a tertiary IBD center.

Molecular Manipulations and Intestinal Stem Cell-Derived Organoids in Inflammatory Bowel Disease.

The pathogenesis of inflammatory bowel diseases (IBD) involves genetic predisposition, environmental factors, and a broadly dysregulated intestinal immune response to the commensal intestinal microflora. The interface between genetic predisposition and environmental factors is reflected in the epigenetic regulation at the transcriptional level. Treatment targets now involve mucosal and histological healing, but the future might additionally include normalization of intestinal cellular functions also at the molecular level, for example comprising complete restoration of phenotypic, genotypic, and epigenetic states.

[Practical guide to the use of thiopurinesin patients with inflammatory bowel diseases].

Despite the increasing availability of biological treatment in recent years, thiopurines remain an important treatment option in patients with inflammatory bowel diseases (IBD) both as monotherapy and in combination therapy with biologicals. Pre-treatment screening of thiopurine-methyltransferase activity and monitoring of thiopurine metabolites during treatment are essential to optimize the effectiveness and safety of thiopurines. This review provides an evidence-based practical guide to prescribing and monitoring thiopurines in patients with IBD.