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Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
Anti-TNF strategies in stenosing and fistulizing Crohn's disease
Martin H Holtmann1, Markus F Neurath
1First Department of Medicine, Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany.
Background:
Stenoses and fistulas are frequent complications in patients with Crohn's disease (CD). They represent a major diagnostic and therapeutic challenge and surgical intervention is often required. The availability of novel, anti-TNF strategies for therapy has raised the question as to what extent these new treatment options have impact on the clinical decision-making process regarding the necessity for surgery.
Discussion:
A short overview of the current pathophysiological understanding of CD, focusing on the immunology of the intestinal mucosa, is given. Then the problems of proper clinical management of stenoses and fistulas are addressed. With regard to symptomatic stenoses, attention will be given to novel diagnostic tools for the distinction between inflammatory and fibrotic stenoses, and our clinical experience with the treatment of symptomatic inflammatory stenoses with infliximab will be discussed. With regard to fistulizing CD, the data that are currently available for medical therapy are summarized with special reference to the studies on the efficacy of anti-TNF treatment.
Conclusion:
With regard to moderately and severe inflammatory stenoses, medical treatment with infliximab may be an option after careful assessment of the inflammatory nature of the stenosis and exclusion of a septic focus. With regard to fistulas, anti-TNF treatment is a valuable option that is likely to improve the clinical outcome. Based on the available data, however, anti-TNF treatment cannot yet replace surgical intervention when necessary. Prospective trials of medical therapy and a combination of medical and surgical therapy for complex fistulas and internal fistulas are needed to define the potential and the limitations of these novel therapeutic approaches.
Insights
Anti-TNF therapies like infliximab offer options for inflammatory Crohn
Area of Science:
- Gastroenterology and Immunology
- Inflammatory Bowel Disease Research
Background:
- Crohn's disease (CD) frequently presents with stenoses and fistulas, posing significant diagnostic and therapeutic challenges.
- Surgical intervention is often required for these complications.
- The advent of anti-tumor necrosis factor (anti-TNF) therapies prompts re-evaluation of surgical necessity.
Purpose of the Study:
- To review the pathophysiology of CD, focusing on intestinal mucosal immunology.
- To address clinical management strategies for stenoses and fistulas in CD.
- To evaluate the impact of anti-TNF therapies on surgical decision-making for CD complications.
Main Methods:
- Overview of current understanding of CD pathophysiology and immunology.
- Discussion of diagnostic tools for differentiating inflammatory versus fibrotic stenoses.
- Summary of available data on medical therapies, particularly anti-TNF treatments, for fistulizing CD.
Main Results:
- Infliximab may be suitable for moderately to severely inflammatory stenoses after excluding sepsis.
- Anti-TNF treatment shows promise for improving clinical outcomes in fistulizing CD.
- Current data suggest anti-TNF therapies do not yet replace necessary surgical interventions.
Conclusions:
- Anti-TNF therapy is a valuable option for fistulizing CD and inflammatory stenoses.
- Further prospective trials are needed to define the role of medical and combined therapies for complex fistulas.
- Careful assessment of stenosis nature and exclusion of sepsis are crucial before initiating infliximab.
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