FRI0327 Abatacept Decreases the Activation of not Only CD4+ T Cells but Also CD14+CD16+ Monocytes and CD86+ Memory B Cells in A Correlation with Disease Activity – Single Center Prospective Cohort Study in Biologics-Naive Rheumatoid Arthritis Patients –
Authors: J. Kikuchi, H. Kameda, K. Yoshimoto, K. Suzuki, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Inflammaroty cells and cytokines have crucial roles in pathogenesis of RA.[1] Although abatacept has same efficacy as cytokine inhibitors, its way of efficacy is different and unique because it is not thought to be direct to cytokines.[2,3] It is important to elucidate the effects of abatacept to inflammaroty cells and cytokines. <h3>Objectives</h3> To examine the effect of abatacept by the associations of activated subsets of peripheral blood mononuclear cells (PBMCs), cytokines and clinical and structural data in RA patients in clinical prospective cohort. <h3>Methods</h3> Fifty-one biologics-naïve RA patients were prospectively evaluated. Multiple subsets of PBMCs with their activation markers and 9 serum cytokines including interleukin (IL)-6 and tumor necrosis factor (TNF) α were sequentially measured by flowcytometry and high sensitivity electrochemiluminescense assay. Relationships between activated subsets of PBMCs, serum cytokines, the disease activity and radiographic progression were evaluated. <h3>Results</h3> Mean disease activity score (DAS) 28-ESR decreased from 5.33 at baseline to 3.43 at week 24. The numbers of HLA-DR+CD4, OX40+CD4, HLA-DR+Th1, HLA-DR+Th2, HLA-DR+Th17, regulatory T cells (Treg) and HLA-DR+Treg significantly decreased at week 24. The ratio of CD69 expression on monocytes also decreased. Changes of HLA-DR expression on Th1, Treg, CD14+CD16+ monocytes and CD86 expression on memory B cells were statistically correlated with those of disease activity (ρ =0.29, p=0.048, ρ =0.35, p=0.016, ρ =0.35, p=0.016 and ρ =0.30, p=0.041, respectively). Change of CD86 expression on memory B cells was correlated with those of CRP, ESR, MMP-3, RF and change of the number of CD86+ B cells was correlated with that of serum IL-6 level (ρ =0.31, p=0.037). Also at the baseline, the expression correlated with serum IL-6 (ρ =0.39, p=0.007). IL-6 levels significantly decreased in patients with EULAR good response (p=0.016). Radiographic progression at week 24 significantly correlated with the baseline serum IL-6 (ρ =0.30, p=0.038) and changes of HLA-DR expression on CD14+CD16+ monocytes and CD161 expression on CD56brightCD16- NK cells (ρ =0.29, p=0.057 and ρ = -0.38, p=0.012). <h3>Conclusions</h3> The chronological analysis of peripheral blood in RA patients suggests abatacept inhibits activation of not only CD4+ T cells including Treg but also CD86+ memory B cells and CD14+CD16+ monocytes. In addition, CD56brightCD16- NK cells and serum IL-6 were associated with radiographic progression. <h3>References</h3> McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. The New England journal of medicine 2011;365(23):2205-19. Bathon J, Robles M, Ximenes AC, et al. Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Annals of the rheumatic diseases 2011;70(11):1949-56. Weinblatt ME, Schiff M, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis and rheumatism 2013;65(1):28-38. <h3>Disclosure of Interest</h3> J. Kikuchi Consultant for: Pfizer Japan Inc., H. Kameda: None declared, K. Yoshimoto: None declared, K. Suzuki: None declared, T. Takeuchi Grant/research support: Abott Japan Co., LTD., Astellas Pharma, Bristol- Myers K.K., Chugai Pharmaceutical Co., LTD., Daiichi Sankyo Co., LTD., Eisai Co., LTD., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nippon Shinyaku Co., LTD., Otsuka Pharmaceutical, Pfizer Japan Inc., Sanofi- aventis K.K., Santen Pharmaceutical, Takeda Pharmaceutical Co., LTD., Teijin Phrma Ltd., Consultant for: Astra Zeneca, K.K., Eli-Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., Speakers bureau: Abott Japan Co., LTD., Bristol-Myers K.K., Chugai Pharmaceutical Co., LTD., Eisai Co., LTD., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., LTD. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1255