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 antipsoriatic activity. However, the ideal dosing regimen for treating psoriasis was not established.


OBJECTIVE
We examined the safety and efficacy of denileukin diftitox in patients with severe plaque-type psoriasis.


METHODS
This was a cohort dose-escalation trial. Patients were administered denileukin diftitox on 3 consecutive days every other week. Patients were evaluated for toxicity, improvement in psoriasis, immunogenicity, and serum levels.


RESULTS
Thirty-five patients were treated at 3 dose levels. Eight patients had a 50% decrease or more in Psoriasis Area and Severity Index score from baseline (0/10 at 0.5 microg/kg per day, 1/10 at 1.5 microg/kg per day, and 7/15 at 5 microg/kg per day). Adverse events primarily consisted of constitutional events and skin reactions.


CONCLUSIONS
The potential antipsoriatic activity of denileukin diftitox demonstrated in this study was comparable to that observed in other psoriasis studies with this agent. However, this dosing regimen was better tolerated than the dosing regimen used in the last study with denileukin diftitox in psoriasis patients.
Martin
A
A
Department of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Gutierrez
E
E
Muglia
J
J
McDonald
C J
CJ
Guzzo
C
C
Gottlieb
A
A
Pappert
A
A
Garland
W T
WT
Bagel
J
J
Bacha
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004167:Diphtheria Toxin; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007376:Interleukin-2; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011506:Proteins / Q000008:administration & dosage* / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins; D012449:Safety
D004167:Diphtheria Toxin; D007376:Interleukin-2; D011506:Proteins; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox