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

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/mm3 at 6 months versus 856 CD4+ T cells/mm3 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.