Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series.
OBJECTIVE
To assess the feasibility of a study design that may determine whether subcutaneous administration of the interleukin-2 receptor antibody daclizumab can safely reduce the dependence on standard systemic corticosteroids or other immunosuppressive regimens in patients with sight-threatening, noninfectious intermediate uveitis, posterior uveitis, or panuveitis.


METHODS
Prospective, multicenter, nonrandomized, noncomparative, open-label interventional trial.


METHODS
Fifteen patients, 5 each at 3 clinical centers, with noninfectious intermediate, posterior, or panuveitis, who require a currently stable immunosuppression regimen of systemic corticosteroids and/or other systemic treatments to control noninfectious intraocular inflammation.


METHODS
After enrollment and baseline ophthalmic evaluations, 2 induction treatments were given 2 weeks apart using subcutaneous (SC) daclizumab at 2 mg/kg. Subcutaneous daclizumab maintenance treatments were then continued every 2 weeks at 1 mg/kg for 6 months. The initial immunosuppression load was tapered over 8 to 12 weeks in a staggered fashion beginning with the first induction treatment. Safety evaluations were performed at each treatment visit, with a primary efficacy evaluation at 12 weeks and a repeat efficacy evaluation at 26 weeks.


METHODS
Best-corrected visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] method) with a concurrent taper of concomitant systemic immunosuppression medication load (tabulated by use of a weighted scoring system) was assessed; target for success was defined as a 50% or greater reduction in concomitant immunosuppression load by 12 weeks while maintaining visual acuity within 5 ETDRS letters of baseline. Ocular inflammation was assessed at each visit with standardized grading scales.


RESULTS
Ten of 15 patients (67%) receiving SC daclizumab treatments every other week successfully achieved the primary efficacy end point of reducing their concomitant immunosuppression load by at least 50% while maintaining their baseline visual acuity at 12 and 26 weeks. Subcutaneous daclizumab injections were well tolerated with no serious adverse events observed during the 6 months of treatments, although 3 patients experienced possibly related, nonserious adverse events.


CONCLUSIONS
Subcutaneous daclizumab induction treatments at 2 mg/kg followed by 1 mg/kg maintenance treatments every other week seems safe and, in most cases, may reduce the concomitant immunosuppressive load required to treat noninfectious uveitis for 12 to 26 weeks.
Nussenblatt
Robert B
RB
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892, USA.
Peterson
Jan S
JS
Foster
C Stephen
CS
Rao
Narsing A
NA
See
Robert F
RF
Letko
Eric
E
Buggage
Ronald R
RR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004341:Drug Evaluation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D015864:Panuveitis / Q000188:drug therapy*; D010865:Pilot Projects; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000276:immunology; D012449:Safety; D015867:Uveitis, Intermediate / Q000188:drug therapy*; D015866:Uveitis, Posterior / Q000188:drug therapy*; D014792:Visual Acuity
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D000077561:Daclizumab