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Drugs for Treatment of Ulcerative Colitis in IBD01:29

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Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
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Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
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Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
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Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
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Related Experiment Video

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Chinese Herbal Retention Enema for the Treatment of Ulcerative Colitis
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Anti-MADCAM therapy for ulcerative colitis.

Sherman Picardo1, Remo Panaccione1

  • 1Inflammatory Bowel Disease Unit, Department of Gastroenterology, University of Calgary, Calgary, AB, Canada.

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|November 12, 2019
PubMed
Summary

Ontamalimab (SHP647) targets mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to reduce immune cell migration in ulcerative colitis (UC). This therapy shows promise for UC management with demonstrated safety and efficacy in early trials.

Keywords:
SHP647Ulcerative colitisanti-MAdCAMinflammatory bowel diseaseontamalimab

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Area of Science:

  • Immunology
  • Gastroenterology
  • Pharmacology

Background:

  • Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is crucial for lymphocyte trafficking in inflammatory conditions like ulcerative colitis (UC).
  • Targeting MAdCAM-1 presents a promising therapeutic strategy for managing UC.
  • Intestinal immune cell trafficking is increasingly recognized as a key factor in UC pathogenesis.

Purpose of the Study:

  • To review preclinical and clinical data on ontamalimab (SHP647), a MAdCAM-1 inhibitor.
  • To evaluate the safety and efficacy of ontamalimab in the context of UC treatment.

Main Methods:

  • Summary of preclinical research on ontamalimab.
  • Analysis of available clinical trial data (Phase II) for ontamalimab.
  • Comparison of ontamalimab's mechanism and safety profile with existing UC therapies.

Main Results:

  • Ontamalimab (SHP647) is a fully human monoclonal antibody inhibiting MAdCAM-1.
  • Phase II clinical trials demonstrated the safety and efficacy of ontamalimab.
  • The targeted mechanism suggests a potentially superior safety profile compared to systemic immunosuppressants.

Conclusions:

  • Ontamalimab inhibits UC pathogenesis by blocking lymphocyte-endothelial cell adhesion via MAdCAM-1.
  • The drug has shown promise in Phase II trials, warranting further investigation.
  • Phase III trial results are anticipated to determine ontamalimab's role in UC therapy.