voclosporin and Uveitis

To date cyclosporine is the only immunosuppressive drug approved for the treatment of uveitis in Germany. However, side effects often limit its use in daily practice. Voclosporin (Luveniq) represents a next generation calcineurin inhibitor which had shown efficacy in an animal model of experimental autoimmune uveitis as well as in clinical trials for the prevention of renal allograft rejection and for plaque psoriasis. The LUMINATE program included three prospective, randomized, double-masked, placebo-controlled multicenter trials which demonstrated the efficacy and tolerability of voclosporin 0.4 mg/kg b.i.d. in noninfectious intermediate and posterior uveitis and panuveitis. In Europe, the Marketing Approval Application (MAA) of voclosporin for the treatment of uveitis was submitted to the European Medicines Agency (EMA) in February 2010 and could be approved in March 2011.

Topics: Cyclosporine; Humans; Immunosuppressive Agents; Injections, Intra-Arterial; Randomized Controlled Trials as Topic; Treatment Outcome; Uveitis

To test the therapeutic effectiveness of voclosporin against experimental autoimmune uveoretinitis (EAU) in rats and to evaluate its effect on human T cells.. EAU was induced by immunization with a uveitogenic protein. Voclosporin administration, by subcutaneous injection, began on day (d) 0 or d7 after immunization. Treatment effectiveness was evaluated in vivo using clinical EAU scoring (d7-d13) and histopathologic evaluation of enucleated eyes after experimental termination. Rodent lymphocytes were harvested from lymph nodes on d14 for antigen-specific proliferation assays. The effect of voclosporin on human T-cell proliferation and cytokine secretion was examined in vitro.. Voclosporin prevented EAU development in rats receiving medium and high preventive doses, whereas high-dose voclosporin administration effectively treated EAU. Lymphocytes from animals treated with voclosporin had decreased antigen-specific proliferation in vitro compared with lymphocytes from untreated animals. No evidence of abnormal ocular histopathology was found in the eyes from animals that received high doses of therapeutic voclosporin. Using human T cells, voclosporin inhibited human T-cell proliferation up to 100-fold. Furthermore, voclosporin treatment of human T cells significantly reduced pan T-cell effector responses.. Voclosporin effectively suppressed uveoretinitis in an animal model that imitates the human inflammatory ocular disease by inhibiting lymphocyte proliferation. In addition, voclosporin effectively inhibited human T-cell proliferation and function in vitro. The authors report the first evidence supporting the application of voclosporin to treat intraocular inflammation.

Topics: Animals; Autoimmune Diseases; Cyclosporine; Cytokines; Disease Models, Animal; Eye Proteins; Humans; Immunosuppressive Agents; Injections, Subcutaneous; Lymphocyte Activation; Male; Rats; Rats, Inbred Lew; Retinitis; Retinol-Binding Proteins; T-Lymphocytes; Treatment Outcome; Uveitis