Advances in immunology and genetics have identified new therapeutic targets to control
inflammation and symptoms in patients with
inflammatory bowel diseases (IBD). Despite the success of anti-TNF
therapies in the treatment of IBD, a considerable proportion of patients are refractory to treatment, highlighting an unmet medical need for new
therapies. Molecules that direct the trafficking of inflammatory cells, such as the α4β7
integrin, are attractive targets for new
drug candidates. The α4β7
integrin is involved in lymphocyte recruitment to the normal and inflamed gut mucosa, and the lymphoid tissue. The pan-α4
integrin neutralizing mAb,
natalizumab, is not gut-selective but has demonstrated efficacy in IBD. However, treatment was associated with the occurrence of
progressive multifocal leukoencephalopathy, which has limited its use, especially in Europe.
Vedolizumab (MNL-0002), Millennium
Pharmaceutical's gut-specific, α4β7
integrin-neutralizing mAb, does not affect peripheral blood cell counts and appears to lack systemic effects. Data from phase II clinical trials of
vedolizumab demonstrated efficacy with an attractive safety profile, especially in
ulcerative colitis. Large phase III, multicenter trials in both
ulcerative colitis and
Crohn's disease will provide valuable data for the ongoing development of
vedolizumab, which might evolve as a new anti-inflammatory treatment option for the management of
therapy-refractory patients.