Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: results of a pilot, multicenter, multiple-dose, placebo-controlled study.
BACKGROUND
OKTcdr4a (IMUCLONE) is a humanized anti-CD4 IgG4 monoclonal antibody that retains the binding and in vitro immunosuppressive properties of the parent murine antibody. Psoriasis is a chronic disease for which treatment with multiple doses of monoclonal antibodies is likely to be required for adequate control.


OBJECTIVE
This study was performed to test the efficacy and safety of OKTcdr4a, given in sequential courses over a period of several weeks, in the treatment of moderate to severe psoriasis vulgaris.


METHODS
Twenty-eight patients (45.6 +/- 10.1 years of age) were studied, with a mean pretreatment Psoriasis Area and Severity Index (PASI) score of 18.3. In the first double-blind phase of the study, patients were randomized to receive OKTcdr4a as a 225 mg/course (low dose), 750 mg/course (high dose), or placebo divided into 3 identical infusions over a 5-day period. After 42 days, patients who met the criteria for re-treatment with OKTcdr4a were re-treated with the 750 mg/course in an open phase of the study.


RESULTS
After the double-blind course of treatment, the mean PASI decreased by 11% in the placebo group, by 4% in the low-dose group, and by 17% in the high-dose group at 15 days. Twenty patients met the criteria for re-treatment (ie, did not experience a decrease in PASI score of 50% at 42 days). They were re-treated with OKTcdr4a at 43 days with the 750 mg/course in the open phase of the study. By day 99, the mean PASI score decreased from 19.9 at baseline to 17 in those patients who had received either placebo or low-dose OKTcdr4a followed by high-dose OKTcdr4a. In contrast, the mean PASI score decreased from 17.4 at baseline to only 7.7 in those patients who had received high-dose OKTcdr4a for both courses. Sustained CD4 saturation was not necessary for sustained clinical response. No patients had significant changes in circulating CD4(+) T-cell counts. The infusions were well tolerated.


CONCLUSIONS
Targeting CD4 using sequential treatments with a humanized monoclonal antibody (OKTcdr4a) may offer another therapeutic option for the treatment of moderate to severe psoriasis.
Gottlieb
A B
AB
Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. gottliab@umdnj.edu
Lebwohl
M
M
Shirin
S
S
Sherr
A
A
Gilleaudeau
P
P
Singer
G
G
Solodkina
G
G
Grossman
R
R
Gisoldi
E
E
Phillips
S
S
Neisler
H M
HM
Krueger
J G
JG
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011565:Psoriasis / Q000188:drug therapy*; D012720:Severity of Illness Index
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G; C079851:OKT4A monoclonal antibody