Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis.
J Rheumatol
; 33(11): 2162-6, 2006 Nov.
Article
em En
| MEDLINE
| ID: mdl-17014006
ABSTRACT
OBJECTIVE:
Abatacept, a soluble selective costimulation modulator, selectively modulates T cell activation via the CD80/CD86CD28 costimulation pathway. Data from a Phase II trial showed efficacy in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate when treated with abatacept (10 mg/kg or 2 mg/kg). To determine the mechanism of action of abatacept, we analyzed changes in the serum levels of inflammatory biomarkers in the patients enrolled in this trial.RESULTS:
Following 12 months' treatment, serum levels of interleukin 6 (IL-6), soluble IL-2 receptor, C-reactive protein, soluble E-selectin, and soluble intercellular adhesion molecule-1 were significantly lower in patients receiving abatacept 10 mg/kg versus placebo. Smaller reductions in tumor necrosis factor-a and rheumatoid factor were also observed in the abatacept 10 mg/kg group compared with the placebo group. Although there was no evidence for efficacy of the 2 mg/kg dose, small reductions in inflammatory biomarkers at this dosage support the biologic effect of this therapy.CONCLUSION:
These findings reveal the antiinflammatory and immunomodulatory effects of abatacept in patients with RA, and are consistent with the concept that modulating T cell activation improves clinical signs and symptoms and inhibits the progression of structural damage. These data suggest that selective modulation of the CD80/CD86CD28 pathway with abatacept may affect several inflammatory cell types and cytokines that are involved in the proinflammatory cascade.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Proteína C-Reativa
/
Receptores de Interleucina-2
/
Interleucinas
/
Imunoconjugados
/
Imunossupressores
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
J Rheumatol
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos