Review article: anti-adhesion therapies for inflammatory bowel disease.

Abstract

BACKGROUND:

A high proportion of patients with inflammatory bowel disease (IBD) do not achieve clinical remission with the current therapies including mesalazine (mesalamine), immunossupresants (IMS) and antibodies against tumour necrosis factor (anti-TNF). Moreover, IMS and anti-TNF involve a nonnegligible risk for infections and/or malignancies. The anti-adhesion molecules are one of the most interesting new treatments because of their gut-selectivity.

AIM:

To review the physiopathology of the adhesion molecules and the current drugs targeting this mechanism.

METHODS:

We performed a literature review in PubMed and in clinicaltrials.gov using the terms 'anti-adhesion molecules', 'inflammatory bowel disease', 'natalizumab', 'vedolizumab', 'AMG181', 'Etrolizumab', 'PF-00547659', 'AJM300', 'Alicaforsen' and 'CCX282-B' up to November 2013.

RESULTS:

A total of eight drugs were found including those targeting the α4β1, α4β7 or αEβ7 integrins as well as the ICAM-1 and MAdCAM-1 addressins and the chemokine receptor 9. The rationale for these drugs is the blockade of gut-homing T lymphocytes and the ones targeting the α4β7/MAdCAM-1 interaction presented the most promising results in luminal disease. Vedolizumab, an α4β7 antibody, has completed phase 3 trials with very positive results especially for ulcerative colitis. However, many questions remain unanswered such as the effect of these therapies in perianal disease and extraintestinal manifestations.

CONCLUSIONS:

The blockade of the α4β7/MAdCAM-1 interaction and especially vedolizumab is an effective and safe gut-specific treatment for IBD. Further studies are needed to clarify the efficacy and safety of the other anti-adhesion drugs and to define the specific indications of these therapies in the different scenarios of IBD.

• Authors: T Lobatón, S Vermeire, G Van Assche, P Rutgeerts
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 39 Issue 6 Pg. 579-94 (Mar 2014) ISSN: 1365-2036 [Electronic] England
• PMID: 24479980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Cell Adhesion Molecules
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Cell Adhesion Molecules (antagonists & inhibitors)
• Colitis, Ulcerative (drug therapy, physiopathology)
• Humans
• Inflammatory Bowel Diseases (drug therapy, physiopathology)
• T-Lymphocytes (immunology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)