TCZ is currently approved in the USA for RA, particularly in treatment refractory cases. such as iontophoresis (EGP-437) and intravitreal injection (sirolimus) for the treatment of NIU’ uveitis has also been discussed. 1. Introduction Local and systemic corticosteroids are the mainstay of treatment for all patients with noninfectious uveitis (NIU); however, long Compound K term use of steroids can lead to both systemic and local adverse effects, such as cataracts, glaucoma, and metabolic disorders, among several others [1]. Increasing efforts are being made to develop a treatment option that will limit corticosteroid use and, therefore, decrease the risk of its associated adverse effects. Current guidelines recommend the addition of immunomodulatory therapy (antimetabolites, calcineurin inhibitors, alkylating agents, Compound K and tumor necrosis factor- (TNF-) alpha inhibitors) when inflammation cannot be controlled with 10?mg/day of prednisone within three months. Although this approach decreases the risks associated with corticosteroid use, immunomodulatory therapy (IMT) in itself has been associated with toxicities and has limited efficacy in some patients, further highlighting the need for a safer alternative to corticosteroids [2]. The index review article focuses primarily on the new therapeutic options for NIU, including novel agents and established drugs with innovative delivery systems. 2. Therapies in Development 2.1. AIN457 (Secukinumab) IL-17 was first identified in rodent T-cell hybridoma and subsequently cloned in CD4 + T-cells in 1995. IL-17 is produced by TH17 cells and mediates its actions through a heterotrimeric receptor composed of two IL-17RA subunits and one IL-17RC subunit, consequently promoting the expression of antimicrobial peptides and inducing secretion of proinflammatory cytokines, chemokines, and metalloproteinases. New evidence suggests IL-17 activity in immune protection against parasites and viruses; however, in contrast to its protective role, it can also lead to adverse effects that result in tissue damage associated with various human inflammatory diseases such as rheumatoid arthritis (RA), psoriasis, multiple sclerosis (MS), and inflammatory bowel disease (IBD) [3]. Likewise in uveitis, the upregulation of IL-17A in patients with active Adamantiades-Beh?et and Vogt-Koyanagi-Harada (VKH) diseases has led to the targeting of this interleukin in ocular inflammatory diseases [4, 5]. By blocking the pathogenic driver IL-17A, the fully human antibody AIN457 (Novartis Pharmaceutical, Basel, Switzerland) has been shown to interrupt inflammation in patients with RA, psoriasis, and NIU [6]. In an open label study of the safety and tolerability of secukinumab, 16 patients with active chronic NIU were treated with two infusions of AIN457 (10?mg/kg), at baseline and 3 weeks later. The majority of patients responded with a rapid reduction in vitreous haze that was sustained in the following 8 weeks with an increase of visual acuity (VA). No serious adverse events were reported [6]. Following the results of this study, further clinical trials have been initiated to evaluate the efficacy and safety of secukinumab in NIU. Dick et al. recently reported a significant reduction in mean total postbaseline immunosuppressive medication (ISM) scores with no loss in visual acuity (VA) in patients treated with AIN457 for NIU. However, the primary endpoint of the study, that is, the uveitis recurrence in patients receiving secukinumabcompared to the placebo group, was not statistically significant in any study. Secukinumab was associated with a significant reduction in mean total postbaseline ISM score (= 0.019; 300?mg q4w versus placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in IL24 the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. Overall, there was no loss in visual acuity reported in any treatment group during follow-up in all 3 studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the 3 studies [13] (Table 1). Table 1 Clinical trials for emergent therapies in noninfectious uveitis. = 0.047)?antibody [9]EYEGUARD A(Santen Pharmaceutical, Osaka, Japan) is a macrolide antibiotic produced naturally byStreptomyces hygroscopicus, (IL-1antibody, XOMA 052, incited a rapid and sustained reduction in inflammation in seven refractory NIU (Adamantiades-Beh?et disease) patients. This effect was observed without the need to increase the dose of corticosteroids, despite the discontinuation of other immunomodulatory therapies [20]. Following the results of the initial study, three phase III studies, EYEGUARD-A (for patients with active disease), EYEGUARD-B (for patients with Adamantiades-Beh?et’s disease), and EYEGUARD-C (for patients with controlled disease), have been initiated [21]. In these studies, subjects receive three monthly injections of gevokizumab (60?mg) followed by an extended assessment phase of the study that will last 36. Compound K
Categories