title: HuMax-CD4: a fully human monoclonal anti-CD4 antibody for the treatment of psoriasis vulgaris.
abstract: 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.
authors: Department of Dermatology, Gentofte University Hospital, Gentofte, Denmark.
authors: Lone
authors: L
authors: Skov
authors: Knud
authors: K
authors: Kragballe
authors: Claus
authors: C
authors: Zachariae
authors: Erik R
authors: ER
authors: Obitz
authors: Elisabeth A
authors: EA
authors: Holm
authors: Gregor B E
authors: GB
authors: Jemec
authors: Henrik
authors: H
authors: Sølvsten
authors: Hans H
authors: HH
authors: Ibsen
authors: Lone
authors: L
authors: Knudsen
authors: Pia
authors: P
authors: Jensen
authors: Jan H
authors: JH
authors: Petersen
authors: Torkil
authors: T
authors: Menné
authors: Ole
authors: O
authors: Baadsgaard
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D010919:Placebos