Abstract
Purpose: :
This study investigated the efficacy of systemic everolimus in noninfectious uveitis.
Methods: :
Mono-center non-randomized prospective pilot-study with patients (mean age 40 years) with chronic intermediate (n=9) or posterior (n=1) uveitis or panuveitis (n=2) unresponsive to cyclosporine A. Prevalent uveitis complications were cystoid macular edema (n=8), cataract (n=7) and epiretinal membrane formation (n=9). Everolimus was added at 1.0 - 2.5 mg oral daily dosage. The primary outcome evaluated was inactivity of uveitis at 3 months. Secondary outcome measures were uveitis recurrence (two step increase of anterior chamber / vitreous cells) during 12 months of follow up, best-corrected visual acuity (BCVA), cystoid macular edema by means of optical coherence tomography (OCT), and the ability to taper concomitant immunosuppression. CD4+CD25+FoxP3+ cells in peripheral blood were studied by flow-cytometry.
Results: :
At 3 months with everolimus, 11 of 12 patients demonstrated uveitis inactivity. Uveitis recurrence was noted during the follow up in 3 patients, either after CsA tapering (n=2) or - withdrawing (n=1). BCVA remained stable in all participants during the course of the study. Mean foveal thickness was reduced from 308 µm at baseline to 291 µm and 251 µm at 3 and 6 months, respectively. Patients receiving everolimus experienced a 50% dose reduction of prednisone (2 of 3) or cyclosporine A (9 of 12). During prolonged therapy, peripheral blood CD4+CD25+FoxP3+ T cells increased.
Conclusions: :
This is the first study demonstrating that everolimus can improve uveitis. Additive everolimus was effective in severe uveitis not responding to cyclosporine A, and permitted the generation of CD4+FoxP3+ TREG cells.
Clinical Trial: :
www.clinicaltrials.gov NCT00792726 EudraCT number 2006-004876-10
Keywords: inflammation • uveitis-clinical/animal model • drug toxicity/drug effects