title: Emerging biologic therapies in rheumatoid arthritis: cell targets and cytokines.
abstract: OBJECTIVE
  Biologic therapy for rheumatoid arthritis targets specific molecules, both cell-bound and soluble, that mediate and sustain the clinical manifestations of this complex disease. The aim of all the therapeutic strategies is to achieve complete and sustained suppression of inflammation, in the absence of unacceptable short-term and long-term toxicity. Despite the success of the currently available biologic inhibitors of tumor necrosis factor-alpha and interleukin-1, a substantial number of rheumatoid arthritis patients are refractory to these treatments. The purpose of this review is to highlight recent clinical trials of emerging biologic treatments for rheumatoid arthritis.
  
  
  RESULTS
  T cell co-stimulation has been targeted by the use of cytotoxic T lymphocyte-associated antigen 4-Ig, a genetically engineered fusion protein. In a large controlled clinical trial, this nondepleting approach was shown to achieve impressive clinical responses, without evidence of short-term toxicity. Likewise, rituximab, a B cell-deleting monoclonal antibody, was shown in a controlled clinical trial to have sustained benefit in patients with refractory rheumatoid arthritis. Despite profound B cell depletion with rituximab, there was an acceptable safety profile with this treatment. MRA, a monoclonal antibody that inhibits interleukin-6 by binding to its receptor interleukin-6R, demonstrated clinically significant improvement in rheumatoid arthritis and a particularly impressive reduction in the acute phase response.
  
  
  CONCLUSIONS
  The response of rheumatoid arthritis to a wide spectrum of therapeutic strategies attests to the complexity and heterogeneity of the disease and provides further impetus for studies that use these therapies to enhance our understanding of disease pathogenesis.
authors.affiliation: Arthritis Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ramandip
authors.initials: R
authors.lastname: Singh
authors.forename: David B
authors.initials: DB
authors.lastname: Robinson
authors.forename: Hani S
authors.initials: HS
authors.lastname: El-Gabalawy
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D007155:Immunologic Factors