Everolimus for the treatment of uveitis refractory to cyclosporine A: a pilot study.

BACKGROUND: This study investigated the efficacy of everolimus, a potent inhibitor of T lymphocyte proliferation, for treating noninfectious uveitis. The study design was an open-label prospective trial.
METHODS: Twelve patients with severe chronic uveitis (anterior and intermediate n = 9, panuveitis n = 3) refractive to cyclosporine A (CsA) received additional everolimus. MAIN OUTCOME MEASURE: the primary outcome measure was uveitis inactivity at 3 months. Secondary outcome measures were uveitis recurrence, visual acuity (BCVA), laser flare photometry values, cystoid macular edema, and tapering of concomitant corticosteroids and/or immunosuppressive drugs in 12 months with the addition of everolimus and after withdrawing everolimus. Percentages of peripheral blood CD3(+)CD4(+)CD25(+)Foxp3(+) cells were studied.
RESULTS: At month 3 with everolimus, uveitis was inactive in all patients. By 12 months, uveitis had recurred in four patients after tapering (n = 2) or withdrawing (n = 2) CsA. BCVA remained stable in all patients, mean foveal thickness (OCT) was slightly reduced from 308 μm at baseline to 255 μm (p = 0.1), and mean flare values were slightly reduced from 27.8 to 19.3 photons/msec (p = 0.1). It was possible to achieve a 50 % dose reduction of systemic prednisone (n = 8) or CsA (n = 8). After withdrawing everolimus, uveitis recurred in 50 % within 1 month; by 6 months, BCVA dropped ≥2 lines in five patients, and prednisone use increased ≥50 % in four patients. The percentage of peripheral blood CD3(+)CD4(+)CD25(+)FoxP3(+) T cells increased during the everolimus treatment, and dropped after withdrawal.
CONCLUSIONS: Uveitis inactivity was achieved with the addition of everolimus in patients with chronic, CsA-refractive anterior and intermediate uveitis, or panuveitis.