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

J Am Acad Dermatol. 2001 Dec;45(6):871-81. doi: 10.1067/mjd.2001.117852.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Diphtheria Toxin*
  • Drug Administration Schedule
  • Female
  • Humans
  • Interleukin-2*
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Proteins / administration & dosage*
  • Proteins / immunology
  • Psoriasis / drug therapy*
  • Recombinant Fusion Proteins
  • Safety

Substances

  • Diphtheria Toxin
  • Interleukin-2
  • Proteins
  • Recombinant Fusion Proteins
  • denileukin diftitox