Initial Evaluation of Subcutaneous Daclizumab Treatments for Noninfectious Uveitis: A Multicenter Noncomparative Interventional Case Series

Ophthalmology. 2005 May;112(5):764-70. doi: 10.1016/j.ophtha.2004.12.034.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Daclizumab
  • Drug Evaluation
  • Feasibility Studies
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / therapeutic use
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / 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

Substances

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