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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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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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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Related Experiment Video

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Type I interferon antagonists in clinical development for lupus.

Jacqueline L Paredes1, Timothy B Niewold1

  • 1Colton Center for Autoimmunity, New York University School of Medicine , New York, NY, USA.

Expert Opinion on Investigational Drugs
|July 24, 2020
PubMed
Summary

New therapies targeting the type I interferon (IFN) pathway show promise for systemic lupus erythematosus (SLE), an incurable autoimmune disease. While challenges remain, advancements suggest IFN antagonists could soon offer clinical utility for SLE patients.

Keywords:
IFN pathwayLupusautoimmune diseaseclinical trialsinterferonsystemic lupus erythematosustype I IFN antagoniststype I interferon pathway

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Area of Science:

  • Immunology
  • Rheumatology
  • Autoimmune Diseases

Background:

  • Systemic lupus erythematosus (SLE) is a chronic, incurable autoimmune disease with significant unmet therapeutic needs.
  • Current treatments like glucocorticoids and immunosuppressants offer only partial responses.
  • The type I interferon (IFN) pathway is notably activated in over 50% of SLE patients and plays a key pathogenic role.

Purpose of the Study:

  • To review the landscape of emerging therapeutics targeting the type I interferon pathway in SLE.
  • To assess the clinical development and potential utility of these novel therapies.

Main Methods:

  • Literature search using terms 'SLE and interferon antagonists'.
  • Identification and review of therapeutics targeting type I IFN in SLE clinical development.
  • Analysis of therapeutic strategies including monoclonal antibodies and vaccination.

Main Results:

  • Several therapeutics targeting type I IFN in SLE have entered clinical development.
  • Approaches include monoclonal antibodies against type I IFN cytokines and kinoid vaccination.
  • Some agents have shown success, but many have not progressed to Phase III trials.

Conclusions:

  • Type I IFN antagonists have demonstrated partial success in SLE treatment.
  • Challenges include concurrent cytokine abnormalities, imprecise IFN signature readouts, and clinical trial complexities.
  • Despite hurdles, the unmet need and recent success with anifrolumab suggest type I IFN antagonists are likely to become clinically useful for SLE.