Prevalence of endoscopic improvement and remission according to patient-reported outcomes in ulcerative colitis.

Background: Treatment targets for ulcerative colitis are evolving towards achievement of endoscopic improvement and remission in addition to symptom resolution. It remains to be accurately quantified what proportion of patients with symptom resolution have residual endoscopic activity that might warrant treatment modification.

Aim: To quantify the prevalence of endoscopic improvement and remission amongst ulcerative colitis patients with various permutations of patient-reported outcomes.

Development and Validation of a Test to Monitor Endoscopic Activity in Patients With Crohn's Disease Based on Serum Levels of Proteins.

Background & Aims: Noninvasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins.

Methods: We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI], using samples from 278 patients with CD from a multinational training cohort.

Outcome of biological therapies in chronic antibiotic-refractory pouchitis: A retrospective single-centre experience.

Background: In limited retrospective series, infliximab, adalimumab and vedolizumab have demonstrated efficacy in chronic antibiotic-refractory pouchitis. Here, we report single-centre data of all biological therapies in refractory pouchitis.

Methods: We retrospectively assessed all records from patients with ulcerative colitis and ileal pouch -anal anastomosis who received infliximab, adalimumab or vedolizumab for pouchitis.

Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study.

Background: Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse.

Aims: To assess pregnancy and child outcomes of VDZE pregnancies and to compare these results to anti-TNF exposed (TNFE) or both immunomodulatory and biologic unexposed (CON IBD) pregnancies.

Inflammatory Bowel Disease (IBD)-A Textbook Case for Multi-Centric Banking of Human Biological Materials.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition affecting mainly the gastro-intestinal tract with two main entities: Crohn's disease (CD) and ulcerative colitis (UC). Although the exact mechanisms underlying the initial development of IBD are not fully understood, it is believed that an abnormal immune response is elicited against the intestinal microbiota in genetically predisposed individuals. Crucial elements of the etiopathogenesis have been elucidated by research using human biological materials.

Expert consensus: practical algorithms for management of inflammatory bowel disease patients presenting with back pain or peripheral arthropathies.

Background: Spondyloarthritis is the most frequent extra-intestinal manifestation of IBD.

Aim: To present simple strategies to identify and differentiate inflammatory joint pain in IBD patients.

Methods: A panel of Belgian gastroenterologists and rheumatologists developed seven algorithms for IBD patients with joint symptoms based on a Delphi exercise conducted between April and December 2016.

Long-term outcome of immunomodulator use in pediatric patients with inflammatory bowel disease.

Objectives: In the era where new biologicals are entering the market, the place of immunomodulators in the treatment of pediatric inflammatory bowel disease (IBD) needs to be reassessed.

Methods: All children with Crohn's disease (CD) or ulcerative colitis (UC) followed at our center over the last 10 years were reviewed. Children who received conventional therapy (including 5-aminosalicylates, steroids, thiopurines and methotrexate) since diagnosis were included.

The Ulcerative Colitis Response Index for Detection of Mucosal Healing in Patients Treated With Anti-tumour Necrosis Factor.

Background: Surrogate markers that accurately detect mucosal healing [MH] in patients with ulcerative colitis [UC] are urgently needed. Several stool neutrophil-related proteins are currently used as biomarkers for MH. However, the sensitivity and specificity are not sufficient to avoid unnecessary endoscopic evaluations.

Protein Glycosylation as a Diagnostic and Prognostic Marker of Chronic Inflammatory Gastrointestinal and Liver Diseases.

Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver.

How, When, and for Whom Should We Perform Therapeutic Drug Monitoring?

The implementation of therapeutic drug monitoring (TDM) in the inflammatory bowel disease practice has evolved over the years. In the early days, the focus was merely on measuring and reporting drug concentrations. Later, these concentrations were considered in light of target concentrations that are related to clinical response.

Oncostatin M as a new diagnostic, prognostic and therapeutic target in inflammatory bowel disease (IBD).

: Given the high rate of primary and acquired resistance to current inflammatory bowel disease (IBD) treatments, novel drug targets and biomarkers that aid in therapeutic prediction are eagerly awaited. Furthermore, postponing treatment initiation because of a diagnostic delay profoundly affects patient well-being and overall disease evolution. Among the emerging targets and biomarkers, oncostatin M (OSM) has gained much interest in the past few years.

Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling.

Objective: Macrophage interleukin (IL)-10 signalling plays a critical role in the maintenance of a regulatory phenotype that prevents the development of IBD. We have previously found that anti-tumour necrosis factor (TNF) monoclonal antibodies act through Fcγ-receptor (FcγR) signalling to promote repolarisation of proinflammatory intestinal macrophages to a CD206+ regulatory phenotype. The role of IL-10 in anti-TNF-induced macrophage repolarisation has not been examined.

Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients.

Background And Objectives: Vedolizumab has demonstrated efficacy and safety in patients with Crohn's disease [CD] and ulcerative colitis [UC]. Endoscopic outcome data are limited, especially in anti-tumour necrosis factor [TNF] naïve patients. The present study compared endoscopic outcome in anti-TNF naïve and exposed patients, and explored if this was affected by drug exposure.

Reliability of Endoscopic Evaluation of Postoperative Recurrent Crohn's Disease.

Endoscopic evaluation for postoperative recurrence of Crohn's disease (CD) is routinely integrated into clinical practice. The Rutgeerts score (RS) was developed to grade the severity of endoscopic postoperative CD recurrence and has been integrated into clinical practice guidelines and utilized as an endpoint in interventional trials. However, the operating properties of the RS have not been fully assessed.

Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis.

Background & Aims: Maintenance treatment with vedolizumab, a monoclonal antibody that inhibits the gut-selective αβ integrin, is administered intravenously. Some patients might prefer a subcutaneous formulation of vedolizumab for maintenance treatment. Subcutaneous vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis.

Osteonecrosis of the jaw in patients with inflammatory bowel disease treated with tumour necrosis factor alpha inhibitors.

Previous reports have suggested a possible association between tumour necrosis factor alpha (TNF-α) inhibitors, used in the treatment of immune-mediated inflammatory diseases, and medication-related osteonecrosis of the jaw (MRONJ). However, a comprehensive assessment of the frequency and severity of MRONJ caused by these agents is lacking. The aim of this cohort study was to investigate the occurrence of MRONJ in a population of patients with inflammatory bowel disease (IBD) treated with TNF-α inhibitors at a tertiary care medical centre.

Expression Levels of 4 Genes in Colon Tissue Might Be Used to Predict Which Patients Will Enter Endoscopic Remission After Vedolizumab Therapy for Inflammatory Bowel Diseases.

Background & Aims: We aimed to identify biomarkers that might be used to predict responses of patients with inflammatory bowel diseases (IBD) to vedolizumab therapy.

Methods: We obtained biopsies from inflamed colon of patients with IBD who began treatment with vedolizumab (n = 31) or tumor necrosis factor (TNF) antagonists (n = 20) and performed RNA-sequencing analyses. We compared gene expression patterns between patients who did and did not enter endoscopic remission (absence of ulcerations at month 6 for patients with Crohn's disease or Mayo endoscopic subscore ≤1 at week 14 for patients with ulcerative colitis) and performed pathway analysis and cell deconvolution for training (n = 20) and validation (n = 11) datasets.

Evaluating Efficacy, Safety, and Pharmacokinetics After Switching From Infliximab Originator to Biosimilar CT-P13: Experience From a Large Tertiary Referral Center.

Background: The use of infliximab biosimilar CT-P13 has increased in patients with inflammatory bowel disease. Nevertheless, doubts about switching from infliximab originator to biosimilar still exist among patients and health care professionals.

Methods: Our tertiary referral center underwent a mandatory switch from infliximab originator to CT-P13 in 2017.

A Population Pharmacokinetic and Exposure-Response Model of Golimumab for Targeting Endoscopic Remission in Patients With Ulcerative Colitis.

Background: Unlike other anti-tumor necrosis factor alpha antibodies, golimumab does not deliver on its promise of effectiveness for treating patients with ulcerative colitis. We investigated the value of therapeutic drug monitoring for optimizing golimumab therapy.

Methods: We analyzed the golimumab pharmacokinetics data of 56 patients with moderate to severe ulcerative colitis.

Comparison of the EMA and FDA Guidelines on Ulcerative Colitis Drug Development.

Background & Aims: In 2016, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) released revised EMA and new FDA draft guidelines related to the development of drugs intended for the treatment of ulcerative colitis. We sought to compare and contrast the EMA draft guideline with the FDA draft guidance to facilitate further discussion and perhaps harmonization between the 2 guidelines when they are finalized.

Methods: A concordance document was created by arranging like or similar topics addressed by the guidelines side by side in a tabular format.

Impact of first-line infliximab on the pharmacokinetics of second-line vedolizumab in inflammatory bowel diseases.

Background: Very little is known about the impact of the wash-out period on the pharmacokinetics of a second-line biologic.

Objective: The objective of this article is to explore the impact of two different wash-out periods on the pharmacokinetics of vedolizumab and infliximab.

Methods: Patients switching from infliximab to vedolizumab were retrospectively identified.

Fibrogenesis in Chronic DSS Colitis is Not Influenced by Neutralisation of Regulatory T Cells, of Major T Helper Cytokines or Absence of IL-13.

Mechanisms underlying fibrogenesis in chronic colitis are largely unknown. There is an urgent need for clinical markers and identification of targets to prevent, treat and limit intestinal fibrosis. This study investigated the contribution of major T cell cytokines and T regulatory cells (Tregs) to inflammation and fibrosis induced in a model of experimental colitis by oral intake of dextran sodium sulphate (DSS) in wild type and IL-13 knock-out C57Bl/6 mice.

Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn's Disease.

Background & Aims: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy.

Methods: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017.