title: Use of a chimeric monoclonal anti-CD4 antibody in patients with refractory rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the safety, immunogenicity, and biologic effects of chimeric monoclonal anti-CD4 (cM-T412) in patients with refractory rheumatoid arthritis (RA), and to obtain preliminary data on the clinical response to this treatment.
  
  
  METHODS
  Twenty-five patients with active refractory RA were treated with incremental doses (10 to 700 mg) of cM-T412 in an open-label, escalating-dose phase I trial.
  
  
  RESULTS
  Infusion with cM-T412 was followed by an immediate, rapid decline in CD4+ T cells. The level of circulating CD4+ T cells remained depressed in most patients even at 6 months posttreatment. Following antibody infusion, proliferative responses of peripheral blood lymphocytes to mitogens and antigens were determined; mitogen and antigen responses were decreased compared with pretreatment responses. Mitogen responses tended to return to baseline values more rapidly than did responses to antigen. Adverse events included fever (19 patients), which was associated with myalgias, malaise, and asymptomatic hypotension; these symptoms were self-limited and appeared to correlate with transient elevations in interleukin-6. No significant human antibody response to the cM-T412 variable region was detected; only 2 patients developed transiently low levels of antibodies reactive with cM-T412. Significant clinical improvement, defined as > or = 50% decrease in tender joint counts compared with baseline, was noted in 43% of patients at 5 weeks and 33% at 6 months following cM-T412 infusion.
  
  
  CONCLUSIONS
  Treatment of refractory RA with cM-T412 appears to be safe and is associated with sustained decreases in circulating CD4+ T cell counts and depressed in vitro T cell responses. No significant human antichimeric antibody response was detected. Nonblinded assessment of clinical end points suggests that treatment with cM-T412 may have beneficial effects in these patients with refractory RA. A double-blind clinical trial is warranted to determine its clinical efficacy in treating RA.
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham 35294-0012.
authors.forename: L W
authors.initials: LW
authors.lastname: Moreland
authors.forename: R P
authors.initials: RP
authors.lastname: Bucy
authors.forename: A
authors.initials: A
authors.lastname: Tilden
authors.forename: P W
authors.initials: PW
authors.lastname: Pratt
authors.forename: A F
authors.initials: AF
authors.lastname: LoBuglio
authors.forename: M
authors.initials: M
authors.lastname: Khazaeli
authors.forename: M P
authors.initials: MP
authors.lastname: Everson
authors.forename: P
authors.initials: P
authors.lastname: Daddona
authors.forename: J
authors.initials: J
authors.lastname: Ghrayeb
authors.forename: C
authors.initials: C
authors.lastname: Kilgarriff
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera / Q000276:immunology*; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal