Successful in vivo blockade of CD25 (high-affinity interleukin 2 receptor)on T cells by administration of humanized anti-Tac antibody to patients with psoriasis

Background: Daclizumab is a humanized antibody to the alpha-subunit (CD25) of the interleukin 2 (IL-2) receptor that blocks normal IL-2 binding to thi s receptor. Because IL-2 is a major stimulus for T-cell growth, blockade of the IL-2 receptor could be useful in treating T-cell-mediated (autoimmune) diseases. Objective: Our purpose was to determine whether adequate concentrations of antibody were achieved in circulating blood and in psoriatic skin lesions t o saturate CD25 receptors. We also intended to measure clinical effect and safety of this agent when used alone (without other immunosuppressive drugs ) in psoriasis. Methods: Nineteen patients with psoriasis in two centers received daclizuma b at an initial dose of 2 mg/kg, then 1 mg/kg at weeks 2, 4, 8, and 12. To determine whether CD25 was blocked in vivo, flow cytometric studies measure d (1) expression of CD25 on CD3(+) T cells derived from blood and (2) immun ohistochemistry measures of CD25(+) cells done on pretreatment and posttrea tment biopsy specimens. Patients were followed up clinically with photograp hs and Psoriasis Area and Severity Index scores. Results: This study showed a consistent blockade of CD25 in peripheral blue d and tissue during the first 4 weeks of therapy while the dosing was every 2 weeks. Variable desaturation of receptors began after 4 weeks, which cor related with a reversal in disease improvement. Patients with a pretreatmen t Psoriasis Area and Severity Index score of less than 36 showed a mean red uction in severity by 30% at 8 weeks (P = .02). During the 16 weeks of trea tment, a 44.8% decrease in expression of the IL-2 receptor a-subunit was fo und. The absolute T-cell counts were calculated and showed no significant c hanges during the course of the study No significant adverse events were pr oduced by daclizumab during this study. Conclusion: We therefore conclude that daclizumab, is a well-tolerated agen t that blocks CD25 expression in peripheral blood and skin. Furthermore, it may be useful in treating psoriasis in some patients.