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Related Concept Videos

Drugs for Treatment of Ulcerative Colitis in IBD01:29

Drugs for Treatment of Ulcerative Colitis in IBD

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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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Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

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

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

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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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Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

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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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Inflammatory Bowel Disease IV: Pharmacological Management01:29

Inflammatory Bowel Disease IV: Pharmacological Management

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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.
Pharmacologic...
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Inflammatory Bowel Disease I: Ulcerative Colitis01:27

Inflammatory Bowel Disease I: Ulcerative Colitis

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Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
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Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis.

Bruce E Sands1, William J Sandborn1, Remo Panaccione1

  • 1From the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York (B.E.S.); the Division of Gastroenterology, University of California, San Diego, La Jolla (W.J.S.), and the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles (S.T.) - both in California; the Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada (R.P.); Janssen Research and Development, Spring House, PA (C.D.O., H.Z., J.J., O.J.A., K.L., P.S., C.M.); the Gastroenterology Department and INSERM 1256, Nutrition, Genetics, and Environmental Risk Exposure, Nancy University Hospital, Université de Lorraine, Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, University Hospitals Leuven and Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium (G.V.A.); the IBD Center, Department of Gastroenterology, Humanitas Research Hospital and Humanitas University, Milan (S.D.); the Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami (M.T.A.); and the Division of Gastroenterology, Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo (T.H.).

The New England Journal of Medicine
|September 26, 2019
PubMed
Summary

Ustekinumab effectively induced and maintained clinical remission in moderate-to-severe ulcerative colitis patients. This interleukin-12/23 antagonist demonstrated superior efficacy compared to placebo with a similar safety profile.

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Area of Science:

  • Immunology
  • Gastroenterology
  • Pharmacology

Background:

  • Ulcerative colitis (UC) is a chronic inflammatory bowel disease.
  • The efficacy of ustekinumab, an interleukin-12 and -23 antagonist, for UC is not well-established.
  • Targeting IL-12/23 pathways offers a potential therapeutic strategy for UC.

Purpose of the Study:

  • To evaluate ustekinumab's efficacy as induction and maintenance therapy in moderate-to-severe ulcerative colitis.
  • To determine the optimal dosing regimen for ustekinumab in UC patients.
  • To assess the safety and tolerability of ustekinumab in this patient population.

Main Methods:

  • A randomized, double-blind, placebo-controlled trial involving 961 patients with moderate-to-severe UC.
  • Patients received ustekinumab or placebo for 8-week induction therapy.
  • Responders to induction therapy were randomized to receive maintenance therapy with ustekinumab (every 8 or 12 weeks) or placebo for 44 weeks.
  • Clinical remission was defined by the Mayo score.

Main Results:

  • Ustekinumab significantly increased clinical remission rates at week 8 (15.6% vs 5.3%) and week 44 (38.4%-43.8% vs 24.0%) compared to placebo.
  • Serious adverse events were similar between ustekinumab and placebo groups.
  • Long-term safety data showed a low incidence of deaths and cancers.

Conclusions:

  • Ustekinumab is an effective treatment for inducing and maintaining remission in moderate-to-severe ulcerative colitis.
  • The study supports ustekinumab as a valuable therapeutic option for UC patients.
  • Further research may explore long-term outcomes and specific patient subgroups.