Open AccessCampath‐1h, a humanized monoclonal antibody, in refractory rheumatoid arthritis
Author(s) -
Weinblatt Michael E.,
Maddison Peter J.,
Bulpitt Ken J.,
Hazleman Brian L.,
Urowitz Murray B.,
Sturrock Roger D.,
Coblyn Jonathan S.,
Maier Agnes L.,
Spreen William R.,
Manna Vasant K.,
Johnston Jeffrey M.
Publication year - 1995
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780381110
Subject(s) - medicine , rheumatoid arthritis , tolerability , nausea , refractory (planetary science) , vomiting , arthritis , immunology , gastroenterology , monoclonal antibody , lymphocyte , antibody , pharmacology , adverse effect , physics , astrobiology
Objective . To evaluate the biologic response, tolerability, and potential clinical effect of a humanized antilymphocyte monoclonal antibody, CAMPATH‐1H, in patients with rheumatoid arthritis (RA). Methods . Forty adult patients with active, refractory RA were treated with CAMPATH‐1H, given intravenously, in a multicenter, open, single‐dose‐escalation study. Patients were assigned to dose groups of 1, 3, 10, 30, 60, and 100 mg CAMPATH‐1H. Results . There was a profound, immediate, and sustained reduction of the peripheral lymphocyte count; the most susceptible were the levels of CD4+ and CD8+ cells, which remained depressed during the study period. Sixty‐three percent of patients developed antibodies to CAMPATH‐1H. Side effects occurred frequently throughout the first 24 hours following infusion, and included fever, headache, nausea, vomiting, and hypotension. All of the immediate drug toxicities resolved within the initial 24‐hour postdosing period. One patient developed a reactivation of Mycobacterium xenopi infection 10 weeks following infusion. Sixty‐five percent of patients developed a clinical response; the mean duration of response was 2 weeks. Conclusion . CAMPATH‐1H is a lymphocytedepleting antibody that is biologically potent even after single‐dose therapy. There was no correlation between biologic effect and clinical response. Sustained lymphocyte suppression was observed. Acute infusion toxicities were observed in most patients. The role of depleting monoclonal antibodies in the treatment of RA should be reevaluated.