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. Author manuscript; available in PMC: 2015 Sep 18.
Published in final edited form as: Discov Med. 2014 Mar;17(93):155–162.

Table 2.

Selected Traditional Therapies and New Biologics for Treatment of Uveitis and Their Associated Animal Models.

Targeted Pathway
(Therapeutic Modality)
Biological Activity Human Disease(s) (Refs)* Animal Model (Refs)
Calcineurin (CsA, FK-506=tacrolimus) Prevent T cell activation and proliferation by inhibiting the Ca2+/calmodulindependent protein phosphatase, calcineurin Effective in various types of uveitis, often used as corticosteroid sparing agents Rat EAU, monkey EAU
mTOR signaling (rapamycin=sirolimus, everolimus) Interferes with mTOR signaling: inhibits T cell activation by modulating signaling pathways of IL-2, IL-4, and IL-15; promotes Treg induction Systemic pilot study and local Tx in Phase III clinical trial indicate efficacy (Nguyen et al., 2013) Rat EAU (Roberge et al., 1993); Mouse EAU (Hennig et al., 2012)
TNF-α (infliximab, adalimumab, etanercept) Chimeric, fully humanized Abs to TNF-α (inflixi- and adalimumab, respectively) and TNFR-IgG Fc fusion protein (etanercept). The antibodies neutralize soluble and membrane bound forms of TNF-α; fusion protein binds to TNFR and prevents signaling. Infliximab, and more recently adalimumab, show good efficacy in JIA; Etanercept appears not useful for treatment of uveitis. Rat and mouse EAU models (Dick et al., 2004; Dick et al., 1996; Sartani et al., 1996)
IL-6 (tocilizumab) Antibody to IL-6R; blockade of the receptor prevents IL-6 signaling; inhibition of direct proinflammatory effects of IL-6 and indirect such as induction of Th17 response Effective in uveitis patients who failed anti TNF-α therapy Mouse EAU (Haruta et al., 2011; Hohki et al., 2010)
IL-1 (anakinra, rilonacept, gevokizumab) Recombinant IL-1RA (Anakinra) blocks binding of IL-1 to its receptor; engineered IL-1R-Fc fusion protein (Rilonacept) and monoclonal Ab Gevokizumab bind to and neutralize IL-1 Uveitis associated with resistant Behçet’s disease or with CINCA syndrome respond to Anakinra. Rilonacept and Gevokizumab clinical trials pending. Mouse EAU (Lim et al., 2005; Su et al., 2005)
IFN type 1 (IFN-α,IFN-β) Recombinant human IFN-α and IFN-β: mechanism of action poorly defined Extensive experience in various types of uveitis more with IFN-α than with IFN-β. Especially effective in Behçet's disease. (Stubiger et al., 2003; Sun et al., 2011; Suzuki et al., 2002)
IL-2 (daclizumab) Antibody to CD25 (IL-2Rα chain): blockade of high-affinity IL-2R; associated with emergence of suppressive CD56-bright NK cells. Strikingly effective in several small, open-label trials in various types of uveitis, but a randomized, placebo controlled trial for Behçet's disease did not show good efficacy Rat EAU (Higuchi et al., 1991; Nussenblatt, 2002)
CTLA-4 (ligand of CD80 and CD86) (abatacept) CTLA-4-Ig fusion protein: prevents effective costimulation of T cells by antigenpresenting cells, by blocking the CD80 and CD86 molecules. Recent reports indicate that abatacept is highly effective in JIA associated uveitis even in cases where the disease was refractory to immunosuppressive agents and TNF inhibitors Rat EAU (Verwaerde et al., 2003)
IL-12/IL-23 p40 (ustekinumab) Ab to IL-12/23 p40 subunit: inhibits Th1 and Th17 lineage commitment Behçet’s disease single case report (Baerveldt et al., 2013). Clinical trial pending (NCT01647152). Mouse EAU (Tarrant et al., 1998; Yoshimura et al., 2009)
IL-17 (secukinumab= AIN457) Monoclonal Ab to IL-17; IL-17 neutralization An open label trial from Novartis reports efficacy in a mix of chronic intermediate, posterior, and pan uveitis (Hueber et al., 2010) but several placebo controlled trials in Behçet's disease did not meet primary efficacy criteria (Dick et al., 2013) Mouse EAU (Luger et al., 2008)
CD-20 (rituximab) Antibody to the CD20 molecule: depletion of B cells. Mechanisms may include reduction of B cell produced Abs and cytokines (IL-6) and elimination of antigen presentation by B cells to disease associated T lymphocytes. Effective in uveitis and scleritis associated with different systemic syndromes, which was refractory to other treatments, e.g., Wegener’s granulomatosis, Sjogren’s syndrome and JIA Mouse experimental autoimmune encephalomyelitis (Barr et al., 2012; Monson et al., 2011)
CD52 (altemtuzumab= Campath1) Antibody to CD52: Depletion of T cells. New T cells may be “reprogrammed” for tolerance Relatively few patients treated, but efficacy reported in various types of uveitis including Behçet's disease Humanized SCID mice (de Kroon et al., 1996; Watanabe et al., 2006)
*

If other references are not cited, the reader is referred to the following comprehensive recent reviews on biologics in uveitis: (Heiligenhaus et al., 2010; Heo et al., 2012; Larson et al., 2011; Leung and Thorne, 2013; Servat et al., 2012; Takeuchi, 2013).