Garden of therapeutic delights: new targets in rheumatic diseases

Table 1 Examples of targeted therapies for rheumatic diseases

	Target	Representative molecules	Representative clinical trials
Cytokines and growth factors	IL-6 receptor	Tocilizumab	Completed phase III in RA. Phase III for sJIA.
	IL-15	AMG714 mAb	Insufficient efficacy in phase II (RA).
	IL-17	AIN457 mAb	Phase I in RA, psoriasis, and others.
	IL-23/IL-12	Ustekinumab	Phase II for psoriatic arthritis.
	BLyS/BAFF	Belimumab	Lack of efficacy in RA. Phase III in SLE.
	BLyS/BAFF and APRIL	Atacicept	Phase I in RA.
	LTα/LTβ/LIGHT	Baminercept	Lack of efficacy in RA for LTβ (phase II).
B-cell targeting	CD20	Ocrelizumab	Phase II in RA, SLE.
		Ofatumumab	Phase II in RA.
		TRU-015 (SMIP)	Phase II in RA.
	CD22	Epratuzumab	Phase II in SLE.
Costimulation	CD80/CD86	Abatacept	Phase II/III in SLE.
Osteoclasts	RANKL	Denosumab	Decreased erosions in RA (phase II).
Intracellular pathways	JAK1/JAK2/Tyk2	INCB018424	Phase I/II in RA and transplant.
	JAK3	CP-690,550
	Syk	Fostamatinib	Phase II in RA.
	p38	Multiple compounds	Phase II in RA, ankylosing spondylitis, Crohn disease, and other inflammatory diseases.
	PDGF-R, c-kit, c-abl	Imatinib	Phase II in RA and scleroderma.
	ERK/MEK	ARRY-162	Phase II in RA.
	PI3Kγ	AS-605240	Preclinical.
Chemokines and other GPCRs	CCR5	Maraviroc	Phase II in RA.
	Adenosine A3 receptor agonist	IB-MECA (CF101)	Phase II in RA.
Ion channels	P2X7 antagonist	CE-224,535	Phase II in RA.

Many other compounds and targets not listed are also being evaluated. Suffixes: -cept, receptor-antibody fusion protein; -umab, human monoclonal antibody; -zumab, humanized monoclonal antibody. APRIL, a proliferation-inducing ligand; BAFF, B-cell activation factor of the tumor necrosis factor family; BLyS, B-lymphocyte stimulator; ERK, extracellular regulating kinase; GPCR, G-protein coupled receptor; IL, interleukin; JAK, Janus kinase; LIGHT, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells; LT, lymphotoxin; mAb, monoclonal (therapeutic) antibody; MEK, mitogen-activated protein kinase; P13K, phosphatidylinositol 3-kinase; PDGF-R, platelet-derived growth factor receptor; RA, rheumatoid arthritis; RANKL, receptor activator of nuclear factor-kappa B ligand; sJIA, systemic juvenile idiopathic arthritis; SLE, systemic lupus erythematosus; SMIP, small modular immunopharmaceutical; Syk, spleen tyrosine kinase.

ISSN: 1478-6362