Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series.

Abstract

PURPOSE:

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.

DESIGN:

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

PARTICIPANTS:

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.

MAIN OUTCOME MEASURES:

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.

• Authors: Robert B Nussenblatt, Jan S Peterson, C Stephen Foster, Narsing A Rao, Robert F See, Eric Letko, Ronald R Buggage
• Journal: Ophthalmology (Ophthalmology) Vol. 112 Issue 5 Pg. 764-70 (May 2005) ISSN: 1549-4713 [Electronic] United States
• PMID: 15878055 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Immunoglobulin G
• Immunosuppressive Agents
• Receptors, Interleukin-2
• Daclizumab

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Daclizumab
• Drug Evaluation
• Feasibility Studies
• Female
• Humans
• Immunoglobulin G (administration & dosage, therapeutic use)
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Injections, Subcutaneous
• Male
• Middle Aged
• Panuveitis (drug therapy)
• Pilot Projects
• Prospective Studies
• Receptors, Interleukin-2 (immunology)
• Safety
• Uveitis, Intermediate (drug therapy)
• Uveitis, Posterior (drug therapy)
• Visual Acuity