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A Fully Human Monoclonal Anti-CD4 Antibody for the Treatment of Psoriasis Vulgaris

Lone Skov, MD; Knud Kragballe, MD; Claus Zachariae, MD; Erik R. Obitz, MD; Elisabeth A. Holm, MD; Gregor B. E. Jemec, MD; Henrik Sølvsten, MD; Hans H. Ibsen, MD; Lone Knudsen, MD; Pia Jensen, MScPharm; Jan H. Petersen, DVM; Torkil Menné, MD; Ole Baadsgaard, MD

Arch Dermatol. 2003;139:1433-1439.

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.

Design  Multicenter, double-blind, placebo-controlled, randomized clinical trial.

Patients  Eighty-five patients with moderate to severe psoriasis.

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

Main Outcome Measures  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.

From the Department of Dermatology, Gentofte University Hospital, Gentofte, Denmark (Drs Skov, Zachariae, and Menné); Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark (Drs Kragballe and Obitz); Section of Dermatology, Department of Medicine, Roskilde Hospital, Roskilde, Denmark (Drs Holm and Jemec); Department of Dermatology, Odense University Hospital, Odense, Denmark (Drs Sølvsten and Ibsen); Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark (Dr Knudsen); and Genmab A/S, Copenhagen (Ms Jensen and Drs Petersen and Baadsgaard).

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