Lw. Moreland et al., NONDEPLETING HUMANIZED ANTI-CD4 MONOCLONAL-ANTIBODY IN PATIENTS WITH REFRACTORY RHEUMATOID-ARTHRITIS, Journal of rheumatology, 25(2), 1998, pp. 221-228
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.