NONDEPLETING HUMANIZED ANTI-CD4 MONOCLONAL-ANTIBODY IN PATIENTS WITH REFRACTORY RHEUMATOID-ARTHRITIS

Objective. To investigate the safety, tolerability, pharmacokinetics, and immunologic activity of single intravenous infusions (0.2-10 mg/kg ) of Orthoclone OKTcdr4a, a nondepleting humanized anti-CD4 monoclonal antibody (Mab) in patients with rheumatoid arthritis. Methods, Eighte en patients were treated with a single intravenous dose of Mab. Three patients each received 0.2, 0.5, 1.0, 2.0, 5.0, or 10.0 mg/kg of OKTcd r4a. Results, No patient had a significant change in CD4+ T cells in p eripheral blood after treatment. No human antimurine antibodies were d etected. At greater than or equal to 1.0 mg/kg dose level, CD4 recepto r saturation was greater than or equal to 95% 24 h after infusion. At 5.0 mg/kg, CD4 receptor occupancy was a mean of 88% at 6 days after in fusion. At 10 mg/kg, CD4 receptor occupancy was still a mean of 79% 2 weeks after infusion. No significant infusion related adverse events o ccurred. Two subjects had headaches at the time of drug administration . Two subjects were hospitalized for infections (pneumonia, Day 45; ce llulitis, Day 14), which resolved with antibiotic therapy. Conclusion. OKTcdr4a was well tolerated at the doses used and saturation of CD4 r eceptors in peripheral blood could be routinely obtained for over one week with a single infusion of Mab.