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 > or = 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 > or = 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.


CONCLUSIONS
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.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D011993:Recombinant Fusion Proteins; D008727:Methotrexate