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 tumor 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.
Dr Rutgeerts and colleagues from Belgium reviewed the physiopathology of the adhesion molecules and the current drugs targeting this mechanism.
|The blockade of the α4β7/MAdCAM-1 interaction and is a safe gut-specific treatment for IBD|
|Alimentary Pharmacology & Therapeutics|
The team 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 2013.
The team identified a total of 8 drugs 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, the researchers noted that there are many questions remain unanswered such as the effect of these therapies in perianal disease and extraintestinal manifestations.
Dr Rutgeerts' team concludes, "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."