Biologic therapies: lessons from multiple sclerosis.
New evidence points to a possible association of multiple sclerosis (MS) with IBD. Tumour necrosis factor (TNF) is involved in the pathogenesis of MS. Paradoxically, administration of anti-TNF monoclonal antibodies to IBD patients has led to exacerbation of MS or triggered demyelination. TNF receptor 1 (TNFR1) mediates demyelination and TNFR2 mediates remyelination, suggesting that a more selective approach to TNF antagonism may be required for an anti-TNF strategy to be effective in MS. Conversely, interferon treatment for MS may worsen IBD. Anti-lymphocyte trafficking strategies such as alpha4 integrin blockers are effective in both these diseases. Recent advances in small molecule development in this area may provide further effective therapies. Common inflammatory cytokine and signaling pathways may be shared between MS and IBD, such as TNF, interleukin (IL)-12/23, IL-17, CD40 and STAT3. However, in contrast to Crohn's disease, ustekinumab has not shown efficacy in MS. Vitamin D deficiency is a hot topic in both diseases. Several drugs developed for MS, e.g. glatiramer acetate, are also being studied in IBDs. As in rheumatoid arthritis, MS also serves as an example of a chronic relapsing inflammatory disease where disease modification is the goal of treatment based on objective evidence derived from imaging, in turn providing examples of how to conduct IBD studies in future.
Department of Medicine, University of Calgary, Calgary, Alta., Canada. subrata.ghosh@albertahealthservices.ca
Subrata
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Ghosh
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001691:Biological Therapy; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha