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 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,

Interleukin-2 Receptor Targeted Therapy of Ocular Disease of HTLV-1-associated Adult T-cell Leukemia

“…4 Denileukin diftitox has had some effect in rheumatoid arthritis and psoriasis. 5,6 . Scleritis is also thought to be a T-cell-mediated disease with increased HLA-DR and IL-2R expression.…”

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

“…Most have been developed in the treatment of rheumatoid arthritis and are now tested in small case series in ocular inflammatory disease, including inhibition of T-cell activation via suppression of growth factor by inhibiting IL-2 receptor signalling with dacluzimab, 75 co-stimulation of T cells via a fusion protein of CTLA-4 (Abatacept), [76][77][78] inhibiting B-cell responses via the anti-CD20mAb Rituximab, 72,[79][80][81][82][83] or blocking pro-inflammatory cytokines (anti-IL-1, Anakinra; anti-IL-6, Tocilizumab). 59 As for anti-TNF-a treatment, which costs Bd10-15 000/patient/year (compared with od3000/year for conventional therapy) all these treatments are expensive to develop and then institute into clinical practice.…”

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

“…Certain autoimmune conditions, notably those involving inflammation of neurological tissues such as multiple sclerosis (MS) and uveitis, have been shown to be responsive to anti-IL2Ra antibodies (Dunn 2004;Martin 2008;Yeh et al 2008;Kim 2009;Bielekova and Becker 2010). Daclizumab and basiliximab, two anti-IL2Ra antibodies approved for graft rejection, have recently been in phase II trials for MS and uveitis.…”