Tumor Necrosis Factor Blockade for Treatment of Inflammatory Bowel Disease: Efficacy and Safety

Department of Gastrointestinal Medicine, Lankenau Hospital, GI Fellows Office, 1(st) Floor, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA.
Current Molecular Pharmacology 11/2010; 3(3):145-52. DOI: 10.2174/1874-470211003030145
Source: PubMed


Inflammatory bowel disease (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC), is characterized by inflammation of the gastrointestinal tract. In UC, inflammation is confined to the mucosa, initially involving the rectum, and may extend proximally to involve the entire colon. In CD, transmural inflammation may affect any portion of the GI tract. The etiology of these disease processes has remained unclear. Therapies are aimed at reducing inflammation and thereby improving symptomatology and morbidity. Traditional medical therapies have included corticosteroids, aminosalicylates, and immunomodulators. Within the past decade, another class of medications has been utilized targeting Tumor Necrosis Factor (TNF), a key, early signaling molecule in the inflammatory cascade. Increased levels of TNF have been found in the blood, epithelial tissue, and stool of patients with active IBD. Anti-TNF medications can not only have direct effects on immune system components, but they also can ameliorate apoptotic cell death and tight junction compromise in the gastrointestinal epithelium. Several randomized, placebo controlled studies have demonstrated the efficacy of these medications in achieving induction and maintaining remission of disease. Their safety profile, however, remains a concern. There has been a reported association of biologic therapy and increased opportunistic infections. A link between biologic therapy and the development of certain malignancies has also been described. Despite these associations, TNF blockade remains an important therapeutic development in the modern therapy of IBD. The role of barrier breakdown at the tight junction level in IBD, and of TNF induction of barrier disruption, is also discussed.

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Available from: James M. Mullin, Dec 03, 2015
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    • "More recently, the use of biologicals, like infliximab or adalimumab that act by targeting tumor necrosis factor (TNF)-α, a key, early signaling molecule in the inflammatory cascade, has resulted in a higher efficacy in those patients who were resistant to conventional treatment (Ngo et al., 2010). However, and unfortunately, these drug treatments are not devoid of potentially serious side effects, thus limiting their chronic use (Stein and Hanauer, 2000; Ngo et al., 2010). For this reason, it is interesting to develop new strategies that, in combination with safety, could restore the altered immune response that emerges in the inflamed intestine in these conditions. "
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    • "Tumor Necrosis Factor (TNF)-α, produced by macrophages, DCs, neutrophils and T H 1 cells, is responsible for pro-inflammatory signaling pathways, like cytokine production and apoptosis. Anti- TNF-α treatment is one of the most promising therapies in IBD nowadays (Sandborn, 2003; Ngo et al., 2010). The contribution of chemokines to the pathogenesis of IBD stems from a series of clinical and animal model studies (Ajuebor & Swain, 2002; Danese & Gasbarrini, 2005). "
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    • "General opinion is that anti-tumour necrosis factor-alpha (TNF-α) medications, such as infliximab and adalimumab, are more efficacious in the treatment of CD than in the treatment of UC. Furthermore, the safety profile associated with infections and certain malignancies is under discussion (Ngo et al., 2010). Pearce and Lawrance (2007) proposed that careful patient selection may improve infliximab's efficacy. "
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