Initial Evaluation of Subcutaneous Daclizumab Treatments for Noninfectious UveitisA Multicenter Noncomparative Interventional Case Series

Nussenblatt, Robert B.; Peterson, Jerry A.; Foster, C. Stephen; Rao, Narsing A.; See, Robert F.; Letko, Erik; Buggage, Ronald

doi:10.1016/j.ophtha.2004.12.034

Cited by 123 publications

(64 citation statements)

References 19 publications

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“…In a multicenter, interventional case series of patients with uveitis treated with subcutaneous daclizumab, 10 of 15 patients (67%) were able to taper their immunosuppressive medications while on daclizumab, achieving their primary endpoint of a 50% reduction in immunosuppressive medication [26].…”

Section: Discussionmentioning

confidence: 99%

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

Yeh

Wroblewski

Buggage

et al. 2008

Journal of Autoimmunity

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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 highdose 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 2-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-4 male patients and 1 female patient were enrolled. Diagnoses included birdshot retinochoroidopathy (2 patients), Vogt-Koyanagi-Harada's disease, bilateral idiopathic panuveitis and bilateral idiopathic intermediate uveitis. By the 4 th week, four of five patients demonstrated a 2-step decrease in vitreous haze. The other participant did not meet this criterion until week 20, but all 5 patients maintained stability in vitreous haze grade throughout their follow-up periods. At enrollment, mean visual acuity (10 eyes in five 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 leftlower 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,

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Section: Discussionmentioning

confidence: 99%

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

Yeh

Wroblewski

Buggage

et al. 2008

Journal of Autoimmunity

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“…Paradoxically, a promising therapy, for some types of autoimmune uveitis, that is currently in clinical trials employs treatment with daclizumab, a humanized anti-IL-2R Ab (6,61). The mechanism was hypothesized to be direct inhibition of CD25 ϩ effector T cells, but appears to also involve induction of CD56 bright regulatory NK cells (62).…”

Section: Cd4mentioning

confidence: 99%

Hydrodynamic Vaccination with DNA Encoding an Immunologically Privileged Retinal Antigen Protects from Autoimmunity through Induction of Regulatory T Cells

Silver

Agarwal

et al. 2007

The Journal of Immunology

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The eye is an immunologically privileged organ whose Ags serve as targets for experimental autoimmune uveitis (EAU), a model for human uveitis. We used a hydrodynamic i.v. injection of naked DNA to express the uveitogenic retinal Ag interphotoreceptor retinoid-binding protein (IRBP) in the periphery, thus revoking its immune-privileged status. IRBP was expressed in the liver within hours of administration of as little as 10 μg of IRBP-DNA. Vaccinated mice were highly protected from EAU induced by immunization with IRBP for at least 10 wk after vaccination. Protection was partial in a reversal protocol. Mechanistic studies revealed specific hyporesponsiveness to IRBP without immune deviation, no evidence for apoptosis either by the Fas- or Bcl-2-regulated (mitochondrial) pathway and apparent lack of dependence on CD8+ cells, IL-10, or TGF-β. In contrast, depletion of CD25+ cells after vaccination and before challenge markedly abrogated protection. IRBP-specific CD4+CD25high T cells could be cultured from vaccinated mice and transferred protection to unvaccinated, EAU-challenged recipients. In vitro characterization of these cells revealed that they are Ag specific, anergic, express FoxP3, CTLA-4, and glucocorticoid-induced TNFR, and suppress by contact. Thus, expression of IRBP in the periphery by DNA vaccination results in tolerance that acts at least in part through induction of IRBP-specific, FoxP3+CD4+CD25+ regulatory T cells. DNA vaccination may offer a new approach to Ag-specific therapy of uveitis.

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“…Inclusion criteria included the ability to provide written informed consent and comply with study assessments for the full duration of the study (B1 h), age 418 years, and the presence of intermediate, posterior, or pan-uveitis or those with ME secondary to DR, AMD, vein occlusion, or uveitis. In addition, the study eyes had to achieve an ETDRS letter score, after a protocol refraction, of 18 or more letters (Z20/400 Snellen equivalent), had to have vitreous haze of r2 þ as measured by standard National Eye InstituteNussenblatt scales, 22 and had to have ME detected by optical coherence tomography (OCT) defined by central subfield retinal thickness of Z310 mm on spectral domain (SD)-OCT.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal comparison of visual acuity as measured by the ETDRS chart and by the potential acuity meter in eyes with macular edema, and its relationship with retinal thickness and sensitivity

Hatef

Hanout

Moradi

et al. 2014

Eye

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Purpose To evaluate the relationship between visual acuity as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and by the potential acuity meter (PAM) with retinal thickness and sensitivity measured by a combined microperimetry/optical coherence tomography system (OCT). Methods Forty-four patients with macular edema (ME) were included in a prospective observational study. Visual acuity (VA) was assessed using the ETDRS chart (with best correction) as well as by the PAM. Retinal thickness and sensitivity was measured by an automatic fundus perimetry/tomography system. Results Best-corrected VA using the ETDRS chart ranged from 20/20 to 20/400 (median: 20/50). VA measured by the PAM without correction ranged from 20/20 to 20/400 (median: 20/40). The mean retinal thickness was 369.57 mm (s.d.: 140.28 mm) on spectral domain-OCT and the mean retinal sensitivity was 8.12 decibels (dB) (s.d.: 5.78 dB). The mean LogMAR value using the ETDRS chart was 0.43, whereas it was 0.38 using the PAM (P-value: 0.009).Conclusions VA values measured by the PAM were statistically significantly better than those measured by the ETDRS chart in eyes with ME secondary to various retinal vascular and uveitic diseases. VA measured by the PAM may be a more sensitive predictor of macular function than that obtained by ETDRS testing in eyes with ME.

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Initial Evaluation of Subcutaneous Daclizumab Treatments for Noninfectious UveitisA Multicenter Noncomparative Interventional Case Series

Cited by 123 publications

References 19 publications

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

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

Hydrodynamic Vaccination with DNA Encoding an Immunologically Privileged Retinal Antigen Protects from Autoimmunity through Induction of Regulatory T Cells

Longitudinal comparison of visual acuity as measured by the ETDRS chart and by the potential acuity meter in eyes with macular edema, and its relationship with retinal thickness and sensitivity

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