HuMax-CD4: a fully human monoclonal anti-CD4 antibody for the treatment of psoriasis vulgaris

Journal of Drugs in Dermatology, Jan-Feb, 2004 by L. Skov, K. Kragballe, C. Zachariae, E.R. Obitz, E.A. Holm, G.B. Jemec, H. Solvsten, H.H. Ibsen, L. Knudsen, P. Jensen, J.H. Petersen, T. Menne, O. Baadsgaard

The objective of this study was to test the safety and efficacy of a fully human monoclonal anti-CD4 antibody (HuMax-CD4) in the treatment of psoriasis. HuMax-CD4 is a fully human anti-CD4 anti body and its function is to prevent T-cell activation.

The design was a stage 2 multicenter, double-blind, placebo-controlled, randomized trial with a group of eighty-five patients with moderate to severe psoriasis. (Only 55 finished the study) The patients were given once weekly subcutaneous infusions of placebo or HuMax-CD4 at doses of 20, 80, 160, or 280 mg for 4 weeks and were followed up to 12 weeks thereafter.

The authors measured the 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.

The authors found at 7 weeks a mean PASI reduction in all treatment groups: placebo, 8% 20 mg, 12%; 80 mg. 14%; 160 mg, 16%; and 280 mg. 24%. 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. CD8 levels were unchanged and a decrease in soluble IL-2 receptors was observed. Four weeks of treatment with HuMax-CD4 was safe and well tolerated. The most serious adverse drug reaction was a drug eruption and influenza-like symptoms.

The authors concluded that 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.

WASHINGTON WHISPERS APPEARS IN EACH ISSUE AND PROVIDES A SUMMARY OF THE LATEST DRUG TRIALS, STUDIES, AND REACTIONS AVAILABLE TO THE MEDICAL COMMUNITY, AS COLLATED FROM A WEALTH OF INDUSTRY SOURCES.

RELATED ARTICLE: JDD ARTICLE EVALUATION

This was a well developed study with average results. The length of the study was short as compared to other similar studies with Etanercept[R], Alefacept[R] and Efalizumab[R], which have better PASI reduction at 12-16 weeks. Of the above mentioned, only HuMax seems to have reported longer than one clearance for a sub-set of patients, even more so since the subjects were treated with only 4 weeks of therapy. Of interest, there is no mention of psoriatic arthritis in the HuMax[R] trial, as it is only being considered for psoriasis; but it would have been of additional benefit to the readers if HuMax[R] had any effect on joint pain and arthritis. All in all, a longer study would have been more informative but as an initial study this is a well developed one.

Arch Dermatol 2003 Nov; 139(11):1433-9.