A multicenter dose-escalation trial with denileukin diftitox (ONTAK, DAB(389) IL-2) in patients with severe psoriasis

Background: Denileukin diftitox, a fusion protein targeting both malignant and normal activated lymphocytes, has been shown previously to have antipso riatic activity However, the ideal dosing regimen for treating psoriasis wa s not established. Objective: We examined the safety and efficacy of denileukin diftitox in pa tients with severe plaque-type psoriasis. Methods: This was a cohort dose-escalation trial. Patients were administere d denileukin diftitox on 3 consecutive days every other week. Patients were evaluated for toxicity, improvement in psoriasis, immunogenicity, and seru m levels. Results: Thirty-five patients were treated at 3 close levels. Eight patient s had a 50% decrease or more in Psoriasis Area and Severity Index score fro m baseline (0/10 at 0.5 mug/kg per clay, 1/10 at 1.5 mug/kg per day, and 7/ 15 at 5 mug/kg per day), Adverse events primarily consisted of constitution al events and skin reactions. Conclusions. The potential antipsoriatic activity of denileukin diftitox de monstrated in this study was comparable to that observed in other psoriasis studies with this agent. However, this closing regimen was better tolerate d than the closing regimen used in the last study with denileukin diftitox in psoriasis patients.