High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis

Steven Yeh, Keith Wroblewski, Ronald Buggage, Zhuqing Li, Shree K. Kurup, Hatice Nida Sen, Sam Dahr, Pushpa Sran, George F. Reed, Randy Robinson, Jack A. Ragheb, Thomas A. Waldmann, Robert B. Nussenblatt

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Purpose: 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 8 mg/kg at day 0 and 4 mg/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 2 mg/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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalJournal of Autoimmunity
Volume31
Issue number2
DOIs
StatePublished - Sep 2008
Externally publishedYes

Keywords

  • Daclizumab
  • Interleukin-2
  • Intermediate uveitis
  • Panuveitis
  • Posterior uveitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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