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Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

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Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
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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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Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
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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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Interleukin-23 Inhibitors in Inflammatory Bowel Disease.

Pierluigi Puca1,2,3, Simone Parello4, Stefania Colantuono5

  • 1Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy. pierluigi.puca@unicatt.it.

Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
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Summary
This summary is machine-generated.

Interleukin-23 (IL-23) inhibitors like risankizumab, mirikizumab, and guselkumab are highly effective for inflammatory bowel disease, showing durable remission and a good safety profile in clinical trials and real-world use.

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Area of Science:

  • Gastroenterology and Immunology
  • Pharmacology and Therapeutics

Background:

  • Inflammatory bowel disease (IBD) involves chronic intestinal inflammation.
  • Selective inhibition of interleukin-23 (IL-23) targets a key pathway in IBD.
  • IL-23 inhibition aims to reduce inflammation while maintaining host defense.

Purpose of the Study:

  • To evaluate the efficacy and safety of IL-23 inhibitors in IBD.
  • To assess the long-term durability of treatment response.
  • To review real-world evidence supporting IL-23 inhibitor use.

Main Methods:

  • Analysis of Phase II and III randomized controlled trials (RCTs) for risankizumab, mirikizumab, and guselkumab.
  • Review of long-term extension studies for sustained efficacy.
  • Examination of real-world data in diverse patient populations.

Main Results:

  • High clinical remission rates (40-50% UC, >50% CD maintenance) achieved with IL-23 inhibitors.
  • Significant endoscopic and histological improvements observed, particularly with mirikizumab and guselkumab.
  • Durable responses maintained beyond two years, with a favorable safety profile and low adverse event rates.

Conclusions:

  • IL-23 inhibitors are a cornerstone therapy for IBD, offering high efficacy and durability.
  • These agents demonstrate a favorable safety profile for long-term management.
  • Real-world evidence confirms effectiveness in complex and previously treated patient groups.