Review: Local Tumor Necrosis Factor-alpha Inhibition in Inflammatory Bowel Disease

Gareb, B., Otten, A. T., Frijlink, H. W., Dijkstra, G. & Kosterink, J. G. W., Jun-2020, In : Pharmaceutics. 12, 6, 34 p., 539.

Research output: Contribution to journalReview articleAcademicpeer-review

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) are associated with disease activity and severity. Anti-TNF-alpha therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-alpha inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-alpha inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-alpha therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-alpha inhibition in IBD.

Original languageEnglish
Article number539
Number of pages34
Issue number6
Publication statusPublished - Jun-2020


  • inflammatory bowel disease, tumor necrosis factor-alpha, local, topical, site-specific, drug targeting, antibody, antisense, miRNA, prokaryote, eukaryote, PERIANAL CROHNS-DISEASE, CALCIUM-PHOSPHATE NANOPARTICLES, TNF FUSION PROTEIN, ANTI-TNF, ULCERATIVE-COLITIS, GENE-EXPRESSION, COLONIC-MUCOSA, ANTISENSE OLIGONUCLEOTIDE, INTESTINAL INFLAMMATION, INFLIXIMAB THERAPY

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