HuMax-CD4: a fully human monoclonal anti-CD4 antibody for the treatment of psoriasis vulgaris.
BACKGROUND
Psoriasis is characterized by infiltration with mononuclear cells. Especially activated memory CD4+ T cells are critical in the pathogenesis. Interaction between the CD4 receptor and the major histocompatibility complex class II molecule is important for T-cell activation.


OBJECTIVE
To test safety and efficacy of a fully human monoclonal anti-CD4 antibody (HuMax-CD4) in the treatment of psoriasis.


METHODS
Multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients Eighty-five patients with moderate to severe psoriasis.


METHODS
Subcutaneous infusions of placebo or HuMax-CD4 at doses of 20, 80, 160, or 280 mg once weekly for 4 weeks.


METHODS
Psoriasis Area and Severity Index (PASI), investigators' and patients' overall response assessment, adverse events, laboratory assessment including total T-cell and subtype counts, CD4 receptor occupancy, and interleukin 2 receptor levels.


RESULTS
At week 7, mean PASI was reduced in all treatment groups (95% confidence intervals are in parentheses): placebo, 8% (-3% to 19%); 20 mg, 12% (-6% to 27%); 80 mg, 14% (-14% to 35%); 160 mg, 16% (-4% to 33%); and 280 mg, 24% (-10% to 48%). At the highest dose level, 6 (38%) of 16 patients obtained more than 25% reduction of PASI and 3 (19%) obtained more than 50% reduction of PASI. A dose-dependent decrease in total lymphocyte count was seen and was parallel to a dose-dependent decrease in CD4+ T cells. This decrease was due to a decrease in the memory subset, whereas the naive subset was affected to a minor degree. Four weeks of treatment with HuMax-CD4 was safe and well tolerated.


CONCLUSIONS
Treatment with HuMax-CD4 led to a moderate, not statistically significant reduction in PASI. The efficacy results obtained after only 4 weeks of treatment suggest that longer treatment would lead to even further reduction of PASI.
Skov
Lone
L
Department of Dermatology, Gentofte University Hospital, Gentofte, Denmark.
Kragballe
Knud
K
Zachariae
Claus
C
Obitz
Erik R
ER
Holm
Elisabeth A
EA
Jemec
Gregor B E
GB
Sølvsten
Henrik
H
Ibsen
Hans H
HH
Knudsen
Lone
L
Jensen
Pia
P
Petersen
Jan H
JH
Menné
Torkil
T
Baadsgaard
Ole
O
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D010919:Placebos