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 ant ibody that retains the binding and in vitro immunosuppressive properties of the parent murine antibody. Psoriasis is a chronic disease for which treat ment 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 OKTc dr4a, given in sequential courses over a period of several weeks, in the tr eatment of moderate to severe psoriasis vulgaris. Methods: Twenty-eight patients (45.6 +/- 10.1 years of age) were studied, w ith a mean pretreatment Psoriasis Area and Severity Index (PASI) score of 1 8.3. 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 thigh 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 decrease d by 11% in the placebo group, by 4% in the low-dose group, and by 17% in t he high-dose group at 15 days. Twenty patients met the criteria for re-trea tment tie, 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 lo w-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 toler ated. Conclusion: Targeting CD4 using sequential treatments with a humanized mono clonal antibody (OKTcdr4a) may offer another therapeutic option for the tre atment of moderate to severe psoriasis.