Anti-TNF Therapy in Crohn’s Disease

Abstract

Crohn’s disease (CD) accounts for a variety of clinical manifestations or phenotypes that stem from chronic inflammation in the gastrointestinal tract. Its worldwide incidence is increasing including younger or childhood-onset of disease. The natural history of Crohn’s disease is characterized by a remitting and relapsing course that progresses to complications and surgery in most patients. The goals of treatment are to achieve clinical and endoscopic remission, to avoid disease progression and minimise surgical resections. Medical treatment usually features antibiotics, corticosteroids, immunomodulators (thiopurines, methotrexate). Anti-TNF (tumour necrosis factor) therapy was approved for use in Crohn’s disease in 1998, and has changed the paradigm of treatment, leading to improved rates of response and remission in patients. There are significant considerations that need to be borne in mind, when treating patients including immunogenicity, safety profile and duration of treatment.

Biological and clinical significance of T helper 17 cell plasticity

“…In agreement with this, etanercept prevented non‐classic Th1 cell development from Th17 in vitro. Anti‐TNF‐ α treatment is approved for the treatment of several immune‐mediated diseases including Crohn’s disease, rheumatoid arthritis, psoriasis and spondyloarthritis . Abatacept, the CTLA‐4–IgG fusion protein that prevents T‐cell activation by binding to CD80 CD86 on antigen‐presenting cells, has been shown to reduce IFN‐ γ and TNF‐ α production by anti‐CD3 stimulated cells, so indirectly preventing possible Th17 trans‐differentiation .…”

“…45 Anti-TNF-a treatment is approved for the treatment of several immune-mediated diseases including Crohn's disease, rheumatoid arthritis, psoriasis and spondyloarthritis. [89][90][91][92] Abatacept, the CTLA-4-IgG fusion protein that prevents T-cell activation by binding to CD80 CD86 on antigen-presenting cells, has been shown to reduce IFN-c and TNF-a production by anti-CD3 stimulated cells, so indirectly preventing possible Th17 trans-differentiation. 93 Other biologicals targeting IL-12 or IL-23 may also be useful as these cytokines are involved in non-classic Th1 cell generation.…”

Synthesis, activity and mechanism of alkoxy-, carbamato-, sulfonamido-, thioureido-, and ureido-derivatives of 2,4,5-trimethylpyridin-3-ol against inflammatory bowel disease

“…TNF-a is a critical player in the pathogenesis of IBD, which is supported by the most efficacious effects of anti-TNF-a biologics in the clinic 28 . Based on the notion, we examined anti-IBD activity of various compounds against TNF-a-induced monocyte adhesion to colonic epithelial cells, an in vitro model of initial phase of colitis.…”

Structure-based design of a Cortistatin analog with improved immunoregulatory activity against inflammatory bowel disease (IBD)

“…Altogether, these observations position IBD as a major health concern whose treatment is an important priority for our society. Finding specific and safe therapeutic tools to tackle these complex disorders is not trivial and requires an efficient combination of approaches to increase treatment effectiveness, improve patient quality of life and reduce the economic cost 3 .…”