From historical perspectives to modern therapy: a review of current and future biological treatments for Crohn’s disease

Abstract

Crohn's disease (CD) is a debilitating, systemic inflammatory disorder with both gastrointestinal and extraintestinal manifestations. Its existence predates modern medicine, but its precise etiology remains incompletely understood. Most authorities suggest a multifactorial pathogenesis owing to a mixture of genetic disorders, immunologic dysregulation, microbiota disequilibrium and environmental influences. Of these factors, the overactive immunologic response seen in CD appears to be the most promising target of medical therapy. Biological agents comprise a relatively new class of drugs that can induce and maintain remission in moderate to severe CD, as well as in ulcerative colitis. This review will provide an overview of CD, its history, clinical features, pathophysiology, and treatment options focusing on current and future biological agents with an emphasis on drug development, dosage and administration.

Magnetic resonance enterography in Crohn’s disease: How we do it and common imaging findings

“…Moreover, the chronic inflammatory response promotes smooth muscle cell proliferation, collagen accumulation, wall thickening, stenosis and fibrosis of the affected bowel segments with mesenteric fibro-fatty proliferation[8,9]. …”

Current and novel anti-inflammatory drug targets for inhibition of cytokines and leucocyte recruitment in rheumatic diseases

“…Manifestations outside the intestine include rheumatologic symptoms (arthritis, ankylosing spondylitis), dermatologic (skin patches) and ophthalmologic symptoms such as uveitis. Patients may also experience frequent aphthous ulcers in the mouth . Maintenance of inflammatory bowel disease (IBD), including Crohn's, is dependent on the release of pro‐inflammatory cytokines, such as TNF‐α and IL‐6 from immune cells.…”

“…As noted, the development of Crohn's may depend on a combination of genetic and environmental factors leading to an exaggerated immune response to commonly encountered antigens as well as commensal flora found in the intestine. Many genes (more than 160) have been described to possibly be altered in patients with IBD, with some describing a direct pro‐inflammatory link resulting in the infiltration of immune cells which cause damage and alteration of the intestinal crypts . NOD2 is one of the genes first described to be responsible for susceptibility to Crohn's and is a receptor normally used for bacterial recognition, leading to NF‐kB activation and pro‐inflammatory cytokine release.…”

“…Patients may also experience frequent aphthous ulcers in the mouth. [2] Maintenance of inflammatory bowel disease (IBD), including Crohn's, is dependent on the release of pro-inflammatory cytokines, such as TNF-a and IL-6 from immune cells. Murine studies have also identified several environmental and genetic factors which may be involved in the pathogenesis of IBD.…”

“…Many genes (more than 160) have been described to possibly be altered in patients with IBD, with some describing a direct proinflammatory link resulting in the infiltration of immune cells which cause damage and alteration of the intestinal crypts. [2] NOD2 is one of the genes first described to be responsible for susceptibility to Crohn's and is a receptor normally used for bacterial recognition, leading to NF-kB activation and pro-inflammatory cytokine release. Alternations, particular a truncation, in NOD2 have been thought to result in an ineffective clearing of bacteria or suppression of the innate response, leading to exaggerated inflammation.…”