ADMINISTRATION OF DAB(389)IL-2 TO PATIENTS WITH RECALCITRANT PSORIASIS - A DOUBLE-BLIND, PHASE-II MULTICENTER TRIAL

Background: Current therapies for recalcitrant psoriasis focus on immu noregulation and targeting of activated T-lymphocytes rather than kera tinocytes. Previous studies with low doses of the lymphocyte-selective fusion protein DAB(389)IL-2 have shown benefit to patients with psori asis. Objective: We examined the safety and efficacy of DAB(389)IL-2 i n 41 volunteers receiving more frequent and higher doses than in a pre vious trial. Methods: Patients were randomized to receive either place bo 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 S everity Index scores at the end of the study, whereas 24% of all treat ed patients (7 of 29) showed the same improvement. Overall, 3 of 12 (2 5%) patients given placebo as opposed to 12 of 29 (41%) patients treat ed with DAB(389)IL-2 improved to this same extent at some point during the study. The rate of improvement for treated patients was significa ntly greater than for placebo patients (p = 0.04; repeated measures AN OVA). Among treated patients, decreases in Psoriasis Area and Severity Index scores were paralleled by changes in the Physician's Global Ass essment and the Dermatology Life Quality Index. Treatment in ten patie nts was discontinued because of adverse events. Flu-like symptoms were the most common with severity increasing at the two higher doses. Onl y one serious adverse event was reported. This occurred in a patient r eceiving 5 mu g/kg daily who experienced vasospasm and a coagulopathy resulting in arterial thrombosis. Conclusion: Our findings are consist ent with the potential antipsoriatic activity of DAP(389)IL-2 demonstr ated in an earlier study. However, DAB(389)IL-2 was less well tolerate d at this dosing regimen, particularly at the highest dose, and it was too toxic at these doses and schedules to be considered in the routin e treatment of psoriasis.