Crohn’s Disease

Pathophysiology

Crohn’s disease (CD) is a chronic, transmural, and segmental, idiopathic inflammatory disease that can affect any segment of the gastrointestinal tract (GI) from the mouth to the anus but most commonly affects the terminal ileum and proximal colon.1-4 The etiology of CD is unknown, but 3 main factors are thought to influence its pathogenesis: genetics, aberrant immune responses in the gut, and gut microbiota.3,5 Several genes related to immune regulation have been linked with CD, including nucleotide oligomerization domain receptor 2, tumor necrosis factor (TNF), and the autophagy gene ATG16L1. The interleukin 23/ Th17 pathway is also associated with CD.1,5 In genetically susceptible individuals, disease onset can be stimulated by changes in the environment that disrupt the mucosal barrier, alter the balance of gut microbiota, or trigger an exaggerated immune response.1,2,5 Reduced expression of the mucin 1 gene in CD can weaken the mucosal barrier, allowing luminal antigens to infiltrate the intestinal lamina propria.6 An altered gut microbiota can lead to aberrant regulation of mucosal regulatory T cells (Tregs).5 The imbalance of effector T cells (Th1 or Th17 cells, TNF-α, and interleukins 17 and 22) and Tregs (interleukin 10 and transforming growth factor β or interleukin 35) in CD may facilitate and perpetuate intestinal inflammation.1,5,6

Landscape

Ongoing research on therapies for CD include biologic agents targeting the IL-12, IL-23 pathways, Janus kinase inhibitors, anti-adhesion agents, and anti-lymphocyte trafficking molecules.7

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The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

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Clinical trial information is sourced from ClinicalTrials.gov. Information is updated manually as clinical trials are published. The efficacy and safety of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

References

  1. Abraham C, Cho JH. N Engl J Med. 2009;361:2066-2078. PMID:19923578
  2. Silva FA, et al. Gastroenterol Res Pract. 2016;2016:2097274. PMID:28070181
  3. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/9357-crohns-disease
  4. Scott FL, et al. Br J Pharmacol. 2016;173:1778-1792. PMID:26990079
  5. Boyapati R, et al. F1000Prime Rep. 2015;7:44. PMID:26097717
  6. Baugmart DC, Sandborn WJ. Lancet. 2012;380:1590-605. PMID:22914295
  7. Weisshof R, et al. Adv Ther. 2018;35:1746-1762. PMID:30374806