Anti-integrin therapy for inflammatory bowel disease

Table 1 Anti-integrin therapies for inflammatory bowel disease

Drug	Formula	Target	Route	Clinical studies	Summary
Natalizumab	Humanized IgG4 mAb	α4-integrin	i.v.	ENCORE	Induction and maintenance in CD
AJM300	Small molecule	α4-integrin	Oral	Phase IIa	Induction in UC
Vedolizumab	Humanized IgG1 mAb	α4β7-integrin	i.v.	GEMINI 1	Induction and maintenance in UC
				GEMINI 2	Induction and maintenance in CD
				GEMINI 3	Induction in CD
Abrilumab (AMG 181/MEDI 7183)	Fully human IgG2 mAb	α4β7-integrin	s.c.	Phase IIb	Induction in UC
				Phase IIb	Induction in CD
Etrolizumab	Humanized IgG1 mAb	β7-integrin	i.v./s.c.	EUCALYPTUS	Induction in UC
				BERGAMOT	Induction in CD
				HICKORY	Induction in CD
PF-00547659 (SHP647)	Fully human IgG2κ mAb	MAdCAM-1	i.v./s.c.	TURANDOT	Induction in UC
				OPERA	Induction in CD

IgG: Immunoglobulin; mAb: Monoclonal antibody; i.v.: Intravenous; CD: Crohn’s disease; UC: Ulcerative colitis; s.c.: Subcutaneous; MAdCAM: Mucosal addressin cell adhesion molecule.

Table 2 Comparison of properties of anti-tumor necrosis factor and gut-specific anti-integrin therapy

	Anti-TNF therapy	Gut-specific anti-integrin therapy
Mechanism of action	TNF-α inhibitor	α4β7-integrin inhibitor
Available agents	Infliximab (UC, CD)	Vedolizumab (UC, CD)
	Adalimumab (UC, CD)
	Certolizumab pegol (CD)
	Golimumab (UC)
Therapeutic efficacy	Frequent loss of response during maintenance therapy	Modest effect on induction therapy for CD
Side effects	Infections, reactivation of latent tuberculosis, potential risk of lymphoma	Nasopharyngitis, arthralgia, headache, nausea
Immunogenicity	Measure the ADA if available	No significant immunogenicity
	Add immunomodulator (infliximab)

TNF: Tumor necrosis factor; UC: Ulcerative colitis; CD: Crohn’s disease; ADA: Antidrug antibodies.