PCI-32765 dose-dependently inhibits inflammation, bone erosion, cellular infiltration and synovial fluid cytokines/chemokines in CIA models. (a) Mice (n = 12) were treated with PCI-32765 orally once daily. Daily average clinical scores are plotted over 18 days of treatment; *** P < 0.001 compared with vehicle (Mann-Whitney U-test). (b) Using the fluorescent probe PCI-33380 , the percentage of Btk occupied by PCI-32765 in collagen-induced arthritis (CIA) mice was measured in splenocytes collected at three hours (left panel, n = 6) and 24 hours (right panel, n = 6) following last dose (D18) of drug treatment. (c) Average J score was determined following micro-CT scanned reconstructed images of hind legs from CIA study (n = 6). (d) Average cellularity (n = 12) in synovial fluid from the knee of CIA mice following PCI-32765 treatment. Giemsa-Wright stained slides were enumerated for granulocytes, macrophages, and lymphocytes under 100×, and five random fields were scored and averaged. (e) Synovial fluid cytokine and chemokine levels from the 12.5 mg/kg treatment group (n = 12) are shown; * P < 0.05, ** P < 0.01; *** P < 0.001 compared with vehicle, analysis of variance.