Abstract Objective Safety and efficacy of daclizumab during an 11-year period. Design Structured, retrospective chart review. Participants Thirty-nine patients. Methods Patients with chronic, ...noninfectious intermediate and/or posterior uveitis. Results Thirty-nine patients (78 eyes) were treated for a mean of 40.3 months. Visual acuity improved by ≥2 lines in the better eye in 7 patients (18.4%) and worsened by 2 lines in 6 patients (15.8%) with a mean of 2.8 Snellen lines of vision lost per eye. Six eyes with vitreous cell less than grade 2 lost 2 lines of vision and 7 eyes with less than grade 2 vitreous cell improved 2 lines. Mean number of immunosuppressive medications per patient decreased from 1.89 medications/patient to 1.17 medications/patient. The average number of periocular injections per patient was 1.46 (range, 0-9). The mean number of flares was 2.05/patient (range, 0-12), with the rate being 0.62 flares per patient-year. Four patients developed cancer during the course of this study. Mean time to onset of malignancy was 26 months and the mean age in this group was 49 years. Conclusions Daclizumab demonstrated efficacy in the reduction of concomitant immunosuppressive medication, stabilization of visual acuity, and the prevention of uveitic flares in most cases. Dermatologic complications were the most frequently observed adverse event in our series. Four patients developed solid tumor malignancies during this 11-year period.
To evaluate the safety and potential therapeutic activity of humanized anti-IL-2 receptor mAb (Daclizumab) therapy in the treatment of patients with severe, sight-threatening, intermediate and ...posterior noninfectious uveitis, a nonrandomized, open-label, pilot study was performed. Patients with uveitis were treated with a minimum of 20 mg of prednisone, cyclosporine, antimetabolites, or any combination of these agents were eligible. Patients were weaned off their systemic immunosuppressive agents according to a standardized schedule, while ultimately receiving Daclizumab infusions every 4 weeks. Anti-IL-2 receptor antibody therapy, given intravenously with intervals of up to 4 weeks in lieu of standard immunosuppressive therapy, appeared to prevent the expression of severe sight-threatening intraocular inflammatory disease in 8 of 10 patients treated over a 12-month period, with noted improvements in visual acuity. One patient met a primary endpoint with a loss of vision of 10 letters or more from baseline in one eye and another patient discontinued therapy because of evidence of increased ocular inflammation. All patients were able to tolerate the study medications without the need for dose reduction. We report effective long-term use of anti-IL-2 therapy for an autoimmune indication. These initial findings would suggest that anti-IL-2 receptor therapy may be an effective therapeutic approach for uveitis and, by implication, other disorders with a predominant Th1 profile.
Therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make long-term therapy difficult. A long-term (>4 year) ...Phase I/II single armed interventional study using intravenous anti-IL-2 receptor alpha treatments (daclizumab) and a short-term Phase II study evaluating the use of a subcutaneous daclizumab formulation were conducted. Patients were tapered off their systemic immunosuppressive therapy and received daclizumab infusions or subcutaneous injections at intervals varying from 2 to 6 weeks. In the long-term study, seven of ten enrolled patients were tapered from their original immunosuppressive medications and maintained exclusively on repeated daclizumab infusions for control of their uveitis for over 4 years. No patient was permanently removed from therapy for an adverse event ascribed to the medication. The use of 6-week infusion intervals led to recurrence of uveitis, while 2- to 4-week intervals did not. Only one patient developed measurable anti-daclizumab antibodies but this disappeared when subcutaneous therapy was begun. In the short-term study, four of the five patients receiving the subcutaneous formulation met the study endpoints for success within the first 12 weeks. All five were successful by 26 weeks. These studies provide preliminary evidence that regularly administered long-term daclizumab therapy can be given in lieu of standard immunosuppression for years to treat severe uveitis and that subcutaneously administered daclizumab appeared to be a clinically viable treatment strategy. These studies suggest that anti-IL-2 receptor blockade could be useful in the treatment of Th1-mediated autoimmune conditions.
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.
Thirty-two patients with sight-threatening uveitis and a decrease in visual acuity requiring systemic therapy were randomly assigned to either cyclosporine A or G in a dose-escalation study. Groups ...received from 2.5 mg/kg of body weight/day to 10 mg/kg of body weight/day of either drug along with low-dose prednisone. More patients taking cyclosporine G had improved visual acuity and a decrease in macular edema, which occurred more rapidly than in the other group, even at the lower doses tested. No difference in renal function was noted between groups at any doses tested. Four patients receiving cyclosporine G had hepatic alterations, but only one required cessation of the drug. The study indicates the potential usefulness of cyclosporine G, particularly at lower doses (4 mg/kg of body weight/day), which could lower the potential for serious renal complications.
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