Abatacept: a costimulatory inhibitor for treatment of rheumatoid arthritis

Expert Opin Biol Ther. 2005 Sep;5(9):1245-54. doi: 10.1517/14712598.5.9.1245.

Abstract

T cell costimulation is believed to be crucial in orchestrating immune responses that lead to inflammation and destruction in rheumatoid arthritis (RA). Abatacept is a novel recombinant CTLA4Ig fusion protein that selectively modulates costimulation via interrupting the CD28:CD80/86 pathway, resulting in downregulation of T cell activation and multiple ensuing effector mechanisms. Abatacept has been shown to be efficacious, either when given alone or in combination with methotrexate, in patients with active RA, including anti-TNF failures. Improvements in clinical signs and symptoms, slowing of radiological progression, and enhancement in patient function and pain have been reported in clinical trials. Infusions were well-tolerated with a favourable safety profile similar to placebo and no appreciable immunogenicity. Abatacept is the first in a new class of biological response modifiers called costimulatory blockers.

MeSH terms

  • Abatacept
  • Animals
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Humans
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / pharmacokinetics*
  • Immunoconjugates / therapeutic use*
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacokinetics
  • Immunologic Factors / therapeutic use*
  • Infusions, Intravenous
  • Lymphocyte Activation
  • Methotrexate / therapeutic use
  • Randomized Controlled Trials as Topic
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Antirheumatic Agents
  • Immunoconjugates
  • Immunologic Factors
  • Abatacept
  • Methotrexate