High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis.
OBJECTIVE
This study was designed to provide preliminary data regarding the safety and efficacy of high-dose humanized anti-IL-2 receptor (daclizumab) therapy for the treatment of active intermediate, posterior or panuveitis.


METHODS
Five patients were recruited into this non-randomized, prospective pilot study of high-dose intravenous induction daclizumab therapy given at doses of 8mg/kg at day 0 and 4mg/kg at day 14. Patients who did not meet a safety endpoint at the 3-week follow-up evaluation were given the option of continuing therapy with subcutaneous daclizumab at 2mg/kg every 4 weeks for 52 weeks. The primary outcome assessed was a two-step decrease in vitreous haze at day 21. Secondary outcomes evaluated included best-corrected visual acuity, retinal thickness as measured by optical coherence tomography, retinal vascular leakage assessed by fluorescein angiography, anterior chamber and vitreous cellular inflammation.


RESULTS
Four male patients and one female patient were enrolled. Diagnoses included birdshot retinochoroidopathy (two patients), Vogt-Koyanagi-Harada's disease, bilateral idiopathic panuveitis and bilateral idiopathic intermediate uveitis. By the 4th week, four of five patients demonstrated a two-step decrease in vitreous haze. The other participant did not meet this criterion until week 20, but all five patients maintained stability in vitreous haze grade throughout their follow-up periods. At enrollment, mean visual acuity (10 eyes in 5 patients) was 69.2 ETDRS letters and following treatment was 78.2 letters (p<0.12). Anterior chamber cell, vitreous cell, and vitreous haze also improved in the majority of eyes. Adverse events were generally mild except for one episode of left-lower lobe pneumonia requiring hospitalization and treatment.


CONCLUSIONS
This is the first demonstration that high-dose daclizumab can reduce inflammation in active uveitis. Daclizumab was well tolerated but there may be a potential increased risk of infection associated with immunosuppression. All five patients demonstrated a decrease in vitreous haze and measures of intraocular inflammation at final follow-up. The results of this small, non-randomized pilot study support the consideration of high-dose daclizumab therapy in cases of active posterior uveitis.
National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Steven
S
Yeh
Keith
K
Wroblewski
Ronald
R
Buggage
Zhuqing
Z
Li
Shree K
SK
Kurup
Hatice Nida
HN
Sen
Sam
S
Dahr
Pushpa
P
Sran
George F
GF
Reed
Randy
R
Robinson
Jack A
JA
Ragheb
Thomas A
TA
Waldmann
Robert B
RB
Nussenblatt
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D000077561:Daclizumab