Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis.

Author(s): Weisman MH, Durez P, Hallegua D, Aranda R, Becker JC, Nuamah I, Vratsanos G, Zhou Y, Moreland LW

Affiliation(s): Division of Rheumatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd., B-131, Los Angeles, CA 90048, USA. weisman@cshs.org

Publication date & source: 2006-11, J Rheumatol., 33(11):2162-6. Epub 2006 Oct 1.

Publication type: Clinical Trial, Phase II; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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. 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/CD86:CD28 pathway with abatacept may affect several inflammatory cell types and cytokines that are involved in the proinflammatory cascade.