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Nondepleting humanized anti-CD4 monoclonal antibody in patients with refractory rheumatoid arthritis
L W Moreland1, T P Haverty, M C Wacholtz
1Department of Medicine, The University of Alabama at Birmingham, 35294-7201, USA.
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:
Eighteen 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 OKTcdr4a.
Results:
No patient had a significant change in CD4+ T cells in peripheral blood after treatment. No human antimurine antibodies were detected. At > or = 1.0 mg/kg dose level, CD4 receptor saturation was > or = 95% 24 h after infusion. At 5.0 mg/kg, CD4 receptor occupancy was a mean of 88% at 6 days after infusion. At 10 mg/kg, CD4 receptor occupancy was still a mean of 79% 2 weeks after infusion. No significant infusion related adverse events occurred. Two subjects had headaches at the time of drug administration. Two subjects were hospitalized for infections (pneumonia, Day 45; cellulitis, Day 14), which resolved with antibiotic therapy.
Conclusion:
OKTcdr4a was well tolerated at the doses used and saturation of CD4 receptors in peripheral blood could be routinely obtained for over one week with a single infusion of Mab.