Clinical and immunologic effects of a PRIMATIZED anti-CD4 monoclonal antibody in active rheumatoid arthritis: results of a phase I, single dose, dose escalating trial.

OBJECTIVE

The goal of this single infusion, dose escalation study was to evaluate the safety of the PRIMATIZED anti-CD4 monoclonal antibody (Mab), IDEC-CE9.1, in patients with rheumatoid arthritis (RA).

METHODS

Twenty-five patients received single infusions of IDEC-CE9.1 in dose escalation form (0.03 to 4 mg/kg). Cohorts consisted of 3 patients each with seropositive RA. Following treatment, patients were monitored for 2 weeks before initiation of treatment of the next cohort. Peripheral blood samples were taken during and after treatment to measure immune function. Flow cytometry of peripheral blood mononuclear cells and in vitro proliferative responses to antigens and recall antigens were assessed pre and post-treatment. Cell surface markers CD3, CD4 (OKT4 and Leu 3a), CD8, CD20, CD25, CD45Ro, CD45Ra and DR were analyzed, and proliferation to mitogens and recall antigens was measured.

RESULTS

No infusion related adverse events were noted and other drug related adverse events were mild. Reduction in peripheral CD4 T cell number was brief (3 to 7 days) and not associated with infection. CD4 cell surface antigen downmodulation was observed postinfusion. Suppression of CD25 expression was associated with a positive clinical response. In vitro proliferative responses to mitogens and antigen were inhibited for up to one month with no association to positive clinical response.

CONCLUSION

IDEC-CE9.1 appears to have a benign safety profile and may modulate immune function rather than deplete CD4+ T cells.