Treatment of rheumatoid arthritis with monoclonal CD4 antibody M‐T151. Clinical results and immunopharmacologic effects in an open study, including repeated administration

Abstract

Recent experimental and clinical data point to the T helper lymphocyte subset as playing a central role in the pathogenesis of rheumatoid arthritis (RA). Thus, a therapeutic strategy aimed specifically at the CD4 T cell subset is warranted. We treated patients with active RA for 7 days with a daily dose of 20 mg of CD4 monoclonal antibody M‐T151, administered intravenously over 30 minutes. There were no negative side effects. According to changes in the combined parameters of Ritchie articular index, pain assessment, grip strength, and morning stiffness, 6 patients had a good response. Clinical improvement was greatest approximately 2 weeks after termination of the therapy and lasted from 4 weeks to 6 months. Of the serologic parameters of inflammation, only the C‐reactive protein level improved in the patients with a favorable response. Close immunologic monitoring revealed a transient, selective depletion of CD4+ T cells after each infusion. During the entire treatment period, residual circulating CD4+ cells were found to be coated with CD4 antibody, whereas free antibody was detected in the serum only for approximately 8 hours after each infusion. Immediately after infusion, soluble CD4 antigen appeared in the serum. In addition to the cell‐bound CD4 antibody, complement components could be detected on the surface of the remaining CD4+ cells. The proliferative response of peripheral blood mononuclear cells to purified protein derivative was significantly diminished 4 weeks after cessation of antibody treatment. Six patients showed a weak antibody response to mouse immunoglobulin. In 4 of the responders who received a second course of therapy (2 of them as outpatients), a therapeutic effect was noted that was similar to that after the first course. Only 1 patient, who had low titers of serum IgE anti‐mouse Ig antibodies, showed a mild anaphylactic reaction at the end of the second course of therapy. Treatment of RA with the monoclonal CD4 antibody M‐T151 seems to be a promising alternative, although the optimal dose and the regimen of administration are still to be defined.