Intestinal Permeability: The Basics

The authors review some of the more fundamental principles underlying the noninvasive assessment of intestinal permeability in humans, the choice of test markers and their analyses, and the practical aspects of test dose composition and how these can be changed to allow the specific assessment of regional permeability changes and other intestinal functions. The implications of increased intestinal permeability in the pathogenesis of human disease is discussed in relation to findings in patients with Crohn’s disease. A common feature of increased intestinal permeability is the development of a low grade enteropathy, and while quantitatively similar changes may be found in Crohn’s disease these seem to predict relapse of disease. Moreover, factors associated with relapse of Crohn’s disease have in common an action to increase intestinal permeability. While increased intestinal permeability does not seem to be important in the etiology of Crohn’s disease it may be a central mechanism in the clinical relapse of disease.

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Discontinuation of Azathioprine Could Be Considered in Pediatric Patients with Crohn’s Disease who Have Sustained Clinical and Deep Remission

10.21203/rs.3.rs-576160/v1 ◽

2021 ◽

Author(s):

Tae Jong Jeong ◽

Eun Sil Kim ◽

Yiyoung Kwon ◽

Seonwoo Kim ◽

Sang Won Seo ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Combination Therapy ◽

Pediatric Patients ◽

Proportional Hazards ◽

Treatment Strategies ◽

Cox Proportional Hazards ◽

Clinical Relapse ◽

Factors Affecting ◽

Factors Associated

Abstract Few studies have demonstrated treatment strategies about the duration and cessation of medications in patients with Crohn’s disease (CD). We investigated factors affecting clinical relapse after infliximab (IFX) or azathioprine (AZA) withdrawal in pediatric patients with CD on combination therapy. Pediatric patients with moderate-to-severe CD receiving combination therapy were analyzed retrospectively and factors associated with clinical relapse were investigated. Discontinuation of IFX or AZA was performed in patients who sustained clinical remission (CR) for at least two years and achieved deep remission. A total of 75 patients were included. Forty-four patients (58.7%) continued with combination therapy and 31 patients (41.3%) discontinued AZA or IFX (AZA withdrawal 10, IFX withdrawal 15, both withdrawal 6). Cox proportional-hazards regression identified four factors associated with clinical relapse: IFX cessation (hazard ratio; HR 2.982, P=0.0081), formation of antibody-to-IFX (ATI) (HR=3.12, P=0.0373), IFX trough level (TL) (HR=0.581, P=0.003) and 6-thioguanine nucleotide (6-TGN) level (HR=0.978, P<0.001). However, AZA cessation was not associated with clinical relapse (P=0.9021). Even when applied in pediatric patients who meet stringent criteria, IFX cessation increased the relapse risk. However, withdrawal of AZA could be contemplated in pediatric patients with CD who have sustained CR for at least two years and achieved deep remission.

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Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease

Gastroenterology ◽

10.1053/gast.1996.v110.pm8613043 ◽

1996 ◽

Vol 110 (5) ◽

pp. 1395-1403 ◽

Cited By ~ 103

Author(s):

RJ Hilsden ◽

JB Meddings ◽

LR Sutherland

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Acetylsalicylic Acid ◽

Intestinal Permeability ◽

Permeability Changes

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Discontinuation of Azathioprine could be considered in pediatric patients with Crohn’s disease who have sustained clinical and deep remission

Scientific Reports ◽

10.1038/s41598-021-04304-6 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Tae Jong Jeong ◽

Eun Sil Kim ◽

Yiyoung Kwon ◽

Seonwoo Kim ◽

Sang Won Seo ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Combination Therapy ◽

Pediatric Patients ◽

Proportional Hazards ◽

Treatment Strategies ◽

Cox Proportional Hazards ◽

Clinical Relapse ◽

Internal Validation ◽

Factors Associated

AbstractFew studies have demonstrated treatment strategies about the duration and cessation of medications in patients with Crohn’s disease (CD). We investigated factors affecting clinical relapse after infliximab (IFX) or azathioprine (AZA) withdrawal in pediatric patients with CD on combination therapy. Pediatric patients with moderate-to-severe CD receiving combination therapy were analyzed retrospectively and factors associated with clinical relapse were investigated. Discontinuation of IFX or AZA was performed in patients who sustained clinical remission (CR) for at least two years and achieved deep remission. A total of 75 patients were included. Forty-four patients (58.7%) continued with combination therapy and 31 patients (41.3%) discontinued AZA or IFX (AZA withdrawal 10, IFX withdrawal 15, both withdrawal 6). Cox proportional-hazards regression and statistical internal validation identified three factors associated with clinical relapse: IFX cessation (hazard ratio; HR 2.982, P = 0.0081), IFX TLs during maintenance therapy (HR 0.581, P = 0.003), 6-thioguanine nucleotide (6-TGN) level (HR 0.978, P < 0.001). However, AZA cessation was not associated with clinical relapse (P = 0.9021). Even when applied in pediatric patients who met stringent criteria, IFX cessation increased the relapse risk. However, withdrawal of AZA could be contemplated in pediatric patients with CD who have sustained CR for at least 2 years and achieved deep remission.

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Relevance of monitoring transmural disease activity in patients with Crohn’s disease: current status and future perspectives

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211006672 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110066

Author(s):

Rune Wilkens ◽

Kerri L. Novak ◽

Christian Maaser ◽

Remo Panaccione ◽

Torsten Kucharzik

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Symptom Control ◽

Current Status ◽

Clinical Relapse ◽

Cross Sectional ◽

Treatment Targets ◽

Endoscopic Remission ◽

Transmural Inflammation

Treatment targets of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) have evolved over the last decade. Goals of therapy consisting of symptom control and steroid sparing have shifted to control of disease activity with endoscopic remission being an important endpoint. Unfortunately, this requires ileocolonoscopy, an invasive procedure. Biomarkers [C-reactive protein (CRP) and fecal calprotectin (FCP)] have emerged as surrogates for endoscopic remission and disease activity, but also have limitations. Despite this evolution, we must not lose sight that CD involves transmural inflammation, not fully appreciated with ileocolonoscopy. Therefore, transmural assessment of disease activity by cross-sectional imaging, in particular with magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS), is vital to fully understand disease control. Bowel-wall thickness (BWT) is the cornerstone in assessment of transmural inflammation and BWT normalization, with or without bloodflow normalization, the key element demonstrating resolution of transmural inflammation, namely transmural healing (TH) or transmural remission (TR). In small studies, achievement of TR has been associated with improved long-term clinical outcomes, including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. This review will focus on the existing literature investigating the concept of TR or residual transmural disease and its relation to other existing treatment targets. Current data suggest that TR may be the next logical step in the evolution of treatment targets.

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