title: Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig.
abstract: BACKGROUND
  Effective new therapies are needed for rheumatoid arthritis. Current therapies target the products of activated macrophages; however, T cells also have an important role in rheumatoid arthritis. A fusion protein--cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis. CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T-cell activation. A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis.
  
  
  METHODS
  We randomly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig per kilogram of body weight (105 patients), 10 mg of CTLA4Ig per kilogram (115 patients), or placebo (119 patients) for six months. All patients also received methotrexate therapy during the study. The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology (ACR), which define the response according to its extent: 20 percent (ACR 20), 50 percent (ACR 50), or 70 percent (ACR 70). Additional end points included measures of the health-related quality of life.
  
  
  RESULTS
  Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo (60 percent vs. 35 percent, P<0.001). Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group. The group given 10 mg of CTLA4Ig per kilogram had clinically meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey. CTLA4Ig was well tolerated, with an overall safety profile similar to that of placebo.
  
  
  CONCLUSIONS
  In patients with active rheumatoid arthritis who were receiving methotrexate, treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life. CTLA4Ig is a promising new therapy for rheumatoid arthritis.
authors: Center for Rheumatology, Albany, NY 12206, USA. jkremer@joint-docs.com
authors: Joel M
authors: JM
authors: Kremer
authors: Rene
authors: R
authors: Westhovens
authors: Marc
authors: M
authors: Leon
authors: Eduardo
authors: E
authors: Di Giorgio
authors: Rieke
authors: R
authors: Alten
authors: Serge
authors: S
authors: Steinfeld
authors: Anthony
authors: A
authors: Russell
authors: Maxime
authors: M
authors: Dougados
authors: Paul
authors: P
authors: Emery
authors: Isaac F
authors: IF
authors: Nuamah
authors: G Rhys
authors: GR
authors: Williams
authors: Jean-Claude
authors: JC
authors: Becker
authors: David T
authors: DT
authors: Hagerty
authors: Larry W
authors: LW
authors: Moreland
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000906:Antibodies; D018796:Immunoconjugates; D000069594:Abatacept