Administration of DAB389IL-2 to patients with recalcitrant psoriasis:: A double-blind, phase II multicenter trial

Background: Current therapies for recalcitrant psoriasis focus on immunoregulation and targeting of activated T-lymphocytes rather than keratinocytes. Previous studies with low doses of the lymphocyte-selective fusion protein DAB(389)IL-2 have shown benefit to patients with psoriasis. Objective: We examined the safety and efficacy of DAB(389)IL-2 in 41 volunteers receiving more frequent and higher doses than in a previous trial. Methods: Patients were randomized to receive either placebo or 5, 10, or 15 mu g/kg, daily of DAB(389)IL-2 intravenously for 3 consecutive days each week for 4 consecutive weeks with a subsequent 4-week observation period. Results: Of the placebo,group, 17% (2 of 12) exhibited at least 50% improvement from baseline Psoriasis Area and Severity Index scores at the end of the study, whereas 24% of all treated patients (7 of 29) showed the same improvement. Overall, 3 of 12 (25%) patients given placebo as opposed to 12 of 29 (41%) patients treated with DAB(389)IL-2 improved to this same extent at some point during the study. The rate of improvement for treated patients was significantly greater than for placebo patients (p = 0.04; repeated measures ANOVA). Among treated patients, decreases in Psoriasis Area and Severity Index scores were paralleled by changes in the Physician's Global Assessment and the Dermatology Life Quality Index. Treatment in ten patients was discontinued because of adverse events. Flu-like symptoms were the most common with severity increasing at the two higher doses. Only one serious adverse event was reported. This occurred in a patient receiving 5 mu g/kg daily who experienced vasospasm and a coagulopathy resulting in arterial thrombosis. Conclusion: Our findings are consistent with the potential antipsoriatic activity of DAP(389)IL-2 demonstrated in an earlier study. However, DAB(389)IL-2 was less well tolerated at this dosing regimen, particularly at the highest dose, and it was too toxic at these doses and schedules to be considered in the routine treatment of psoriasis.