AUG 07, 2008
NIH researchers report in this article on the effects of initial treatment with high-dose intravenous daclizumab, a monoclonal antibody that acts as an IL-2 receptor inhibitor, in five patients with noninfectious uveitis involving the posterior segment. The research was a phase II open-label nonrandomized pilot study based on the idea, gleaned from previous data from a lymph node biopsy, that the IL-2 receptors in secondary lymphoid organs may not be sufficiently engaged by the usual daclizumab dose. Therefore, higher doses of daclizumab may be required, at least initially.
The patients were treated intravenously with an initial daclizumab8 mg/kg dose and daclizumab 4mg/kg 14 days later, followed by subcutaneous daclizumab 2 mg/kg every four weeks for up to a year. They achieved the study's primary endpoint of a two-step decrease in vitreous haze. They observed a positive trend for the secondary endpoint, increased visual acuity, but the results were not statistically significant. A decrease in anterior chamber cells was not a specific endpoint, but patients did experience improvement in this measure. Additionally, patients were able to decrease their use of other systemic agents, although this change did not reach statistical significance.
Retinal vascular leakage was seen at presentation in one patient and this responded to daclizumab. Cystoid macular edema was seen in four eyes of two patients at baseline and also responded to treatment. Side effects and toxicities were generally either mild or thought to be unrelated to daclizumab use. One patient was diagnosed with a viral syndrome and pneumonia.
Given the small number of patients included in the study and the uncontrolled design, we certainly can't make definitive judgments about daclizumab therapy based on this research. However, the data are certainly very promising and suggest consideration of a loading dose with daclizumab therapy.
Dr. Levinson has no financial interests to disclose.