Voclosporin: a potentially promising therapeutic agent for noninfectious uveitis

Abstract

Voclosporin is a novel calcineurin inhibitor that functions by binding cyclophilin, consequently inhibiting calcineurin activity and preventing the transcription of many genes involved in lymphocyte proliferation and cytokine release. Voclosporin has been shown to be effective in a variety of autoimmune diseases, such as rheumatoid arthritis, psoriasis and renal transplant rejection. Noninfectious uveitis is also an immune-mediated disease which, if left untreated, can cause severe loss of vision. Presently, corticosteroids are the mainstay of therapy in noninfectious uveitis. However, there are several metabolic and ophthalmic adverse effects associated with the long-term use of corticosteroids. Voclosporin has recently been shown in the LX-211 Uveitis Multicenter Investigation of a New Approach to Treatment (LUMINATE) clinical trial program to be effective in the treatment of noninfectious uveitis. With an acceptable sideeffects profile, voclosporin is an exciting addition to the therapeutic options available in the management of noninfectious uveitis.

Emerging Therapies for Noninfectious Uveitis: What May Be Coming to the Clinics

“…These characteristics allowed this agent to be an invaluable immunosuppressant in organ transplantation and other autoimmune conditions such as RA and psoriasis [33]. During the past few years, attention has been gained on Th-1 mediated conditions like dry eye syndrome and uveitis.…”

New Treatment Options for Noninfectious Uveitis

“…The LUMINATE (LX211 Uveitis Multicenter Investigation of a New Approach to TrEatment) studies evaluated the efficacy of voclosporin for noninfectious uveitis in three placebo-controlled, dose-ranging, randomized, multicenter trials (The LUMINATE Active, the LUMINATE Maintenance, and the LUMINATE Anterior) [47]. The studies included a broad spectrum of subjects with a variety of etiologies of uveitis involving the anterior, intermediate, and/or posterior segments and disease status (active and quiescent) that required systemic IMT with or without systemic corticosteroids.…”

“…The studies compared three dosages of voclosporin: 0.2, 0.4, and 0.6 mg/kg b.i.d. with placebo in patients with different types of uveitis [47,48].…”

“…The oral corticotherapy as monotherapy represented nearly 35% of subjects previously using IMT. Additional 30% of subjects were receiving both oral corticosteroids and another immunomodulatory agent, and 28% were being treated with IMT alone [47,48].…”

“…In the LX211-03 (Treatment of Active Anterior Uveitis) study, all treatment groups, including placebo, experienced an improvement in anterior chamber inflammation, resulting in no discernible treatment effect [47,48].…”