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

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 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.

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.

• Authors: 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
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 31 Issue 2 Pg. 91-7 (Sep 2008) ISSN: 0896-8411 [Print] England
• PMID: 18571896 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Immunoglobulin G
• Interleukin-2 Receptor alpha Subunit
• Daclizumab

Topics

• Adult
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Daclizumab
• Dose-Response Relationship, Drug
• Female
• Humans
• Immunoglobulin G (adverse effects, therapeutic use)
• Interleukin-2 Receptor alpha Subunit (immunology)
• Male
• Middle Aged
• Pilot Projects
• Prospective Studies
• Treatment Outcome
• Uveitis (drug therapy)
• Young Adult