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Review
. 2016 Mar 9:10:33-52.
doi: 10.2147/BTT.S71679. eCollection 2016.

Selective biologics for ulcerative colitis and Crohn's disease - clinical utility of vedolizumab

Jill Mv Petkau  1 , Bertus Eksteen  1
Affiliations
Review

Selective biologics for ulcerative colitis and Crohn's disease - clinical utility of vedolizumab

Jill Mv Petkau et al. Biologics. .

Abstract

Inflammatory bowel disease (IBD) encompasses a cluster of different disease phenotypes which are broadly classified into ulcerative colitis and Crohn's disease. Disease pathogenesis is driven by abnormal host immune responses to their resident gut microbiome in genetically susceptible individuals. Clinical disease features and outcomes are heterogenous and not unexpected as over 163 genetic loci are associated with disease susceptibility, and there are great variability in environmental exposures. Despite this variability, there has been relatively few efficacious therapies for particularly moderate-to-severe IBD. Treatment has been dominated by antitumor necrosis alpha agents with significant success but equally potentially serious adverse events. Therapeutic targeting of leucocyte trafficking has emerged as a viable alternative therapy, with vedolizumab being the lead compound. This review focuses primarily on its biological function as a selective gut immunotherapy, its safety and efficacy, and its emerging role as a mainstream therapy in managing IBD.

Keywords: adhesion molecule antagonist; anti-α4β7 integrin; inflammatory bowel disease; leukocyte trafficking; monoclonal antibody; selective gut immunotherapy; tumor necrosis factor alpha.

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Figures

Figure 1
Figure 1
CD103+ expressing dendritic cells (CD103+ DC) present an antigen in the context of MHC class 2 and co-stimulatory signals to naïve T-cells in mesenteric lymph nodes which leads to activation, proliferation, and recognition of the cognate antigen. Note: Gut CD103+ DCs are unique as they also convert retinoic acid which imprints selective gut trafficking molecules such as CCR9 and α4β7. Abbreviations: CD, Crohn’s disease; DC, dendritic cell; MHC, major histocompatibility complex; TCR, T cell receptor.
Figure 2
Figure 2
Drug development targeting different elements of gut-specific trafficking of immune cells in IBD. Note: Vedolizumab and AMG181 targets α4β7, natalizumab targets α4, etrolizumab selectively targets β7, PF-00547659 targets MAdCAM1, GSK-1605786 (CCX-282; Traficet-EN) targets CCR9, and BTT1023 targets VAP1. Manufacturing details: Takeda: Osaka, Japan; Amgen: Thousand Oaks, CA, USA; Elan: Dublin, Ireland; Genentech: South San Francisco, CA, USA; Pfizer: New York, NY, USA; ChemoCentryx: Mountain View, CA, USA; Biotie Therapies: Turku, Finland. Abbreviation: IBD, inflammatory bowel disease.
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