Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis.
OBJECTIVE
Abatacept, a soluble selective costimulation modulator, selectively modulates T cell activation via the CD80/CD86:CD28 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.


CONCLUSIONS
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/CD86:CD28 pathway with abatacept may affect several inflammatory cell types and cytokines that are involved in the proinflammatory cascade.
Weisman
Michael H
MH
Division of Rheumatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd., B-131, Los Angeles, CA 90048, USA. weisman@cshs.org
Durez
Patrick
P
Hallegua
David
D
Aranda
Richard
R
Becker
Jean-Claude
JC
Nuamah
Isaac
I
Vratsanos
George
G
Zhou
Ye
Y
Moreland
Larry W
LW
D000069594:Abatacept; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000737:chemistry*; D004334:Drug Administration Schedule; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007378:Interleukins / Q000097:blood*; D015375:Receptors, Interleukin-2 / Q000097:blood*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D015415:Biomarkers; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D007378:Interleukins; D015375:Receptors, Interleukin-2; D000069594:Abatacept; D002097:C-Reactive Protein