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.


METHODS
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.
Department of Ophthalmology, St. Franziskus Hospital, University of Duisburg-Essen, Muenster, Germany. arnd.heiligenhaus@uveitis-zentrum.de
Arnd
A
Heiligenhaus
Beatrix
B
Zurek-Imhoff
Martin
M
Roesel
Maren
M
Hennig
Daniela
D
Rammrath
Carsten
C
Heinz
D000328:Adult; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D000068338:Everolimus; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010783:Photometry; D010865:Pilot Projects; D011446:Prospective Studies; D012008:Recurrence; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy*; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus