CAMPATH-1H, A HUMANIZED MONOCLONAL-ANTIBODY, IN REFRACTORY RHEUMATOID-ARTHRITIS - AN INTRAVENOUS DOSE-ESCALATION STUDY

Objective. To evaluate the biologic response, tolerability, and potent ial clinical effect of a humanized antilymphocyte monoclonal antibody, CAMPATH-1H, in patients with rheumatoid arthritis (RA). Methods. Fort y adult patients with active, refractory RA were treated with CAMPATH- 1H, given intravenously, in a multicenter, open, single-dose-escalatio n study. Patients were assigned to dose groups of 1, 3, 10, 30, 60, an d 100 mg CAMPATH-1H. Results. There was a profound, immediate, and sus tained reduction of the peripheral lymphocyte count; the most suscepti ble were the levels of CD4+ and CD8+ cells, which remained depressed d uring the study period, Sixty-three percent of patients developed anti bodies to CAMPATH-1H. Side effects occurred frequently throughout the first 24 hours following infusion, and included fever, headache, nause a, vomiting, and hypotension, All of the immediate drug toxicities res olved within the initial 24-hour postdosing period, One patient develo ped a reactivation of Mycobacterium xenopi infection 10 weeks followin g infusion. Sixty-five percent of patients developed a clinical respon se; the mean duration of response was 2 weeks. Conclusion. CAMPATH-1H is a lymphocyte-depleting antibody that is biologically potent even af ter single-dose therapy, There was no correlation between biologic eff ect and clinical response, Sustained lymphocyte suppression was observ ed. Acute infusion toxicities were observed in most patients. The role of depleting monoclonal antibodies in the treatment of RA should be r eevaluated.