Selecting the ideal candidate for Anti-TNF discontinuation in Crohn’s Disease, dream or reality?

© 2021 by the AGA InstituteThe topic of anti-TNF therapy discontinuation for patients with inflammatory bowel disease in long-term remission is of significance for both clinicians and patients, due to safety concerns, adverse effects, and cost. In the current pandemic era, it has regained renewed attention. However, disease relapse has been reported to occur in roughly 50% of patients, highlighting the need for the development of biomarkers that could help in selecting the best candidates for successful stopping.info:eu-repo/semantics/publishedVersio

Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease

Background: Mucosal IL-13 Receptor alpha 2 (IL13RA2) mRNA expression is one of the best predictive markers for primary non-responsiveness to infliximab therapy in patients with inflammatory bowel disease (IBD). The objective of this study was to understand how IL-13Rα2, a negative regulator of IL-13 signaling, can contribute to IBD pathology.Methods:IL13RA2 knockout (KO) and wild type (WT) mice were exposed to dextran sodium sulfate (DSS) in drinking water to induce colitis. Furthermore, mucosal biopsies and resection specimen of healthy individuals and IBD patients before the start of anti-tumor necrosis factor (anti-TNF) therapy were obtained for immunohistochemistry and gene expression analysis.Results: After induction of DSS colitis, IL13RA2 KO mice had similar disease severity, but recovered more rapidly than WT animals. Goblet cell numbers and mucosal architecture were also more rapidly restored in IL13RA2 KO mice. In mucosal biopsies of active IBD patients, immunohistochemistry revealed that IL-13Rα2 protein was highly expressed in epithelial cells, while expression was restricted to goblet cells in healthy controls. Mucosal IL13RA2 mRNA negatively correlated with mRNA of several goblet cell-specific and barrier genes, and with goblet cell numbers.Conclusions: The data suggest that IL-13Rα2 on epithelial cells contributes to IBD pathology by negatively influencing goblet cell recovery, goblet cell function and epithelial restoration after injury. Therefore, blocking IL-13Rα2 could be a promising target for restoration of the epithelial barrier in IBD

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

Introduction: 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.Areas covered: A literature search to June 2019 was performed to identify the most relevant reports on Oncostatin M. The authors summarize the biology of OSM, its role in health and disease, its potential as a diagnostic, prognostic and therapeutic biomarker in the field of IBD and how it might be a drug target of the future.Expert opinion: OSM has diagnostic, prognostic and therapeutic capabilities. High mucosal OSM predicts primary non-response to anti-TNF antibodies. However, one could question whether a single cytokine can capture the complexity and heterogeneity of IBD. Neutralizing OSM in patients with elevated mucosal OSM appears to be attractive and should be considered as a valid option for the first biomarker-stratified, proof-of-concept trial that studies a novel therapeutic compound in IBD.status: publishe

Editorial: a clinical decision tool to identify patients who might benefit most from intensified dosing in the biological era-getting nearer?

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Tofacitinib, two-faced Janus in ulcerative colitis and Crohn's disease?

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Biomarker discovery for personalized therapy selection in inflammatory bowel diseases: Challenges and promises

The past decades witnessed a significant stride in deciphering the pathophysiology of inflammatory bowel disease, which further advanced drug development adding several new biologicals and small molecules to the arsenal of available therapies. Surprisingly, this wealth in therapeutic options did not yield the aspired high durable response rates. In addition, the increase in therapeutic availabilities ignited an increase in research toward biomarkers that could help assign therapies to patients with the highest probability of response. Luckily, major steps have been undertaken in this domain which resulted in the discovery of some interesting biomarkers that are still under validation. However, the pace in which this domain is progressing, the discordance between short-term endpoints in biomarker discovery studies and the ambition of the disease community in modifying disease course, and the uncertainties about the validity of discovered biomarkers highlight the need for a critical appraisal of research conduct in this domain. In this review, we shed light on areas of improvement in biomarker discovery studies that will help optimize the use of available therapies and break the current therapeutic ceiling

Monitoring vedolizumab and ustekinumab drug levels in patients with inflammatory bowel disease: hype or hope?

Therapeutic drug monitoring (TDM) plays a vital role in implementing precision medicine in inflammatory bowel disease (IBD), and may contribute to increased effectiveness, lower rates of drug toxicity and cost savings. While expert panels advocate the use of reactive TDM for anti-tumor necrosis factor (anti-TNF) agents, TDM is not yet widely recommended for non-anti TNF biologicals. We provide an overview of the observational evidence of the value of TDM in case of vedolizumab and ustekinumab. We also shed light on obstacles that need to be addressed before establishing wide acceptance of TDM in the field of IBD. In this respect, new analytical techniques and modelling approaches are being developed to further optimize efficacy of TDM and to facilitate general acceptance of this tool in personalizing IBD management.status: Published onlin