Investigational new drugs in the treatment of inflammatory bowel disease: a review

Figures & data

Figure 1 The cytokine cascade in inflammatory bowel disease.

Abbreviations: IFN, interferon; IL, interleukin; Th, T helper; TLR, Toll-like receptor; TNF, tumor necrosis factor.

Figure 2 Migration of immune cells to the site of inflammation in the gut.

Abbreviation: MadCAM-1, mucosal addressin cell adhesion molecule 1.

Table 1 Selected biological therapy trial update

Drug	Mechanism of action	Development status	Published IBD studies	Trials underway	Number of patients treated	Significant results
Golimumab	Anti-TNFα	Phase II/III	Nil published on IBD. Extensive evidence for use in rheumatoid arthritis, psoriatic arthropathy, ankylosing spondylitis	Induction and maintenance therapy in patients with moderately to severely active ulcerative colitis	Studies recruiting
Tocilizumab	Anti-IL-6 receptor	Phase II	Ito et al^Citation8	No trials underway at present	36 patients with Crohn’s disease	80% clinical response; 20% remission
Ustekinumab	Anti-IL-12/23	Phase II	Sandborn et al^Citation15	Moderately to severely active Crohn’s disease, previously treated with anti-TNF therapy	104 patients with Crohn’s disease	59% response in patients previously treated with anti-TNF-α
Vedolizumab	Anti-α4β7 integrin	Phase III	Feagan et al^Citation34	Induction and maintenance in patients with moderately to severely active Crohn’s disease, ulcerative colitis, and open labeled observational study (GEMINI 1/2/3)	127 patients with Crohn’s disease	37% remission in higher dose treatment group
TNF-kinoid	Immunotherapy	Phase I/II	Rogler et al^Citation6	Phase II in patients with moderate/severe Crohn’s disease	13 patients with Crohn’s disease

Abbreviations: IBD, inflammatory bowel disease; IL, interleukin; TNF, tumor necrosis factor.

ItoHTakazoeMFukudaYA pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active crohn’s diseaseGastroenterol20041264989996

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SandbornWJFeaganBJFedorakRNUstekinumab Crohn’s Disease Study Group. A randomised trial of ustekinumab, a human interleukin-12/23 monoclonal antibody in patients with moderate to severe Crohn’s diseaseGastroenterology20081351130114118706417

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FeaganBGGreenbergGRWildGTreatment of active Crohn’s disease with MLN0002, a humanised antibody to the alpha4-beta7 integrinClin Gastroenterol Hepatol200861370137718829392

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RoglerGMichettiPKrugerFActive therapeutic immunization against TNF with a TNF-kinoid in Crohn’s disease patients: a Phase 1–2 studyGastroenterology2010138Suppl 1517

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