Ulcerative Colitis

Pathophysiology

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease of the colonic mucosa that typically starts in the rectum and spreads proximally through part of or the entire colon in a continuous pattern.1-3 The etiology of UC is unknown but the disease is thought to be triggered by an impaired mucosal barrier, dysbiosis, and dysregulated immune responses.2 In UC, decreased sulfation and secretion of the secretory human colonic mucin subtype 2 (MUC2) may damage the mucosal barrier that separates host immune cells from luminal microbes, leading to increased exposure of the mucosa to the latter.4 UC may result from an exaggerated immune response to commensal enteric microflora in genetically susceptible individuals.1,4 In patients with UC, there is an increased infiltration of innate immune cells (neutrophils, macrophages, dendritic cells, and natural killer T cells) and adaptive immune cells (B and T cells) into the intestinal lamina propria.1,2,4 As a result, local levels of tumor necrosis factor α, interleukin (IL) 1β, interferon γ, and IL-23-Th17 cytokines are elevated.1,4 The inflammatory response in UC may be further amplified by the recruitment of circulating leukocytes to the inflamed intestinal mucosa.1,4

Landscape

The clinical course of UC is unpredictable and ranges from prolonged periods of remission to fulminant disease requiring immediate therapy.5,6 Ongoing research for UC therapies includes biologic agents targeting the IL-12, IL-23 pathways, Janus kinase inhibitors, anti-adhesion agents, anti-lymphocyte trafficking molecules, toll-like receptor agonists, and phosphatidylcholine.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. de Souza HS, Fiocchi C. Nat Rev Gastroenterol Hepatol. 2016;13:13-27. PMID:26627550
  4. Ordás I, et al. Lancet. 2012;380:1606-1619. PMID:22914296
  5. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/10351-ulcerative-colitis
  6. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/symptoms-causes/syc-20353315
  7. Weisshof R, et al. Adv Ther. 2018;35:1746-1762. PMID:30374806