Double‐blind, placebo‐controlled multicenter trial using chimeric monoclonal anti‐cd4 antibody, cm‐t412, in rheumatoid arthritis patients receiving concomitant methotrexate

Abstract Objective . To evaluate the clinical response to and safety of single and repeat doses of a chimeric anti‐CD4 monoclonal antibody, cM‐T412, in patients with rheumatoid arthritis (RA) concomitantly treated with a stable regimen of low‐dose methotrexate. Methods . Sixty‐four patients with refractory RA, who were already receiving stable doses of methotrexate, were randomized into a multicenter, double‐blind, placebo‐controlled trial to receive 3 monthly treatments with either a placebo, or 5, 10, or 50 mg cM‐T412, given intravenously. Results . Using ≥50% improvement in swollen joint counts as a criterion for clinical response, 13%, 13%, 18%, and 13% of patients receiving 50, 10, or 5 mg cM‐T412, or the placebo, respectively, exhibited a clinical response at 3 months of therapy. Using ≥50% improvement in tender joint counts as a measure of clinical efficacy at 3 months, 19%, 13%, 12%, and 6% of patients receiving 50, 10, or 5 mg cM‐T412, or the placebo, respectively, exhibited a clinical response. “Flu‐like” symptoms (fever, chills, rigor) within 24 hours of the infusion occurred more frequently in the groups receiving 50‐mg (29%) and 10‐mg (31%) doses of cM‐T412 than those receiving 5 mg cM‐T412 (12%) or the placebo (13%). Significant CD4+ T cell depletion occurred in the 50‐mg group (mean of 353 CD4+ T cells/mm 3 at 6 months versus 856 CD4+ T cells/mm 3 at baseline). All patients were followed up for 12 months after the final treatment; no opportunistic infectious complications occurred. Conclusion . Treatment with cM‐T412 in this cohort of RA patients who were also taking methotrexate was not associated with clinical efficacy or enhanced toxicity from infectious complications, despite significant peripheral CD4+ T cell depletion.