Su1915 Prediction of Anti-TNF Antibody Responses in Crohn's Disease by Endoscopic Molecular Imaging In Vivo: A Clinical Phase 1 Study

Atreya, Raja; Neumann, Helmut; Neufert, Clemens; Zopf, Yurdagül; Waldner, Maximilian J.; Kießlich, Ralf; Münster, Tino; Kessler, Hermann; Maas, Stefanie; Gebhardt, B; Heimke-Brinck, Ralph; Dörje, Frank; Rau, Tilman T.; Hannappel, Ewald; Neurath, Markus F.

doi:10.1016/s0016-5085(12)62054-x

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“…Interestingly, subsequent clinical therapy with adalimumab revealed that patients with high amounts of mTNF þ cells in the mucosa were significantly more likely to respond to anti-TNF therapy than patients with low amounts of mTNF þ cells. 116 This observation opens new avenues for individualized adalimumab therapy in IBD and suggests that failure to anti-TNF therapy may occur in patients with low amounts of mTNF þ lamina propria cells due to TNF-independent gut inflammation. If this concept holds true, it might be of interest to target the mTNF/TNFR2 interaction specifically in the future rather than total TNF (mTNF plus sTNF).…”

Section: Attacking Key Proinflammatory Pathways In Ibd: Anti-tnf Antimentioning

confidence: 96%

New targets for mucosal healing and therapy in inflammatory bowel diseases

2014

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Healing of the inflamed mucosa (mucosal healing) is an emerging new goal for therapy and predicts clinical remission and resection-free survival in inflammatory bowel diseases (IBDs). The era of antitumor necrosis factor (TNF) antibody therapy was a remarkable progress in IBD therapy and anti-TNF agents led to mucosal healing in a subgroup of IBD patients; however, many patients do not respond to anti-TNF treatment highlighting the relevance of finding new targets for therapy of IBD. In particular, current studies are addressing the role of other anticytokine agents including antibodies against interleukin (IL)-6R, IL-13, and IL-12/IL-23 as well as new anti-inflammatory concepts (regulatory T cell therapy, Smad7 antisense, Jak inhibition, Toll-like receptor 9 stimulation, worm eggs). In addition, blockade of T-cell homing via the integrins α4β7 and the addressin mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) emerges as a promising new approach for IBD therapy. Here, new approaches for achieving mucosal healing are discussed as well as their implications for future therapy of IBD.

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Section: Attacking Key Proinflammatory Pathways In Ibd: Anti-tnf Antimentioning

confidence: 96%