title: Administration of DAB389IL-2 to patients with recalcitrant psoriasis: a double-blind, phase II multicenter trial.
abstract: 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 DAB389IL-2 have shown benefit to patients with psoriasis.
  
  
  OBJECTIVE
  We examined the safety and efficacy of DAB389IL-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 microg/kg daily of DAB389IL-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 DAB389IL-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 microg/kg daily who experienced vasospasm and a coagulopathy resulting in arterial thrombosis.
  
  
  CONCLUSIONS
  Our findings are consistent with the potential antipsoriatic activity of DAB389IL-2 demonstrated in an earlier study. However, DAB389IL-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.
authors.affiliation: Psoriasis Treatment Center of Central New Jersey, East Windsor 08520, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bagel
authors.forename: W T
authors.initials: WT
authors.lastname: Garland
authors.forename: D
authors.initials: D
authors.lastname: Breneman
authors.forename: M
authors.initials: M
authors.lastname: Holick
authors.forename: T W
authors.initials: TW
authors.lastname: Littlejohn
authors.forename: D
authors.initials: D
authors.lastname: Crosby
authors.forename: H
authors.initials: H
authors.lastname: Faust
authors.forename: D
authors.initials: D
authors.lastname: Fivenson
authors.forename: J
authors.initials: J
authors.lastname: Nichols
mesh_terms: D000328:Adult; D000368:Aged; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox