P2-1　Ex vivo functional comparison of baricitinib and tofacitinib for cytokine signaling in human leukocyte subpopulations

抄録

  Object: To determine whether differences in JANUS kinase inhibitors (JAKi), Baricitinib (bari) and tofacitinib (tofa), specificity translate to differences in cellular signal transduction in leukocyte subpopulations stimulated by cytokines, indicated by inhibition of signal transducers of activator transcription (STATs) phosphorylation.

  Methods: Peripheral blood mononuclear cells were obtained from healthy donors. The half maximum inhibitory concentration (IC₅₀) values of STAT phosphorylation were estimated by fitting restricted top 3 parameter logistic curves to 7-point concentration response curves in phenotypically gated leukocyte subpopulations.

  Results: IC₅₀ values for bari and tofa were similar for interleukin (IL)-6 across leukocyte subsets. Tofa was a more potent inhibitor of IL-2, IL-4, IL-15, and IL-21 induced STAT phosphorylation than bari. Both compounds inhibited IL-10- and interferon (IFN)-α-induced STAT phosphorylation similarly. Both compounds inhibited GM-CSF, G-CSF and IFN signaling, with bari exhibiting a greater effect in monocytes than tofa.

  Conclusions: The differences in IC₅₀ for key cytokine stimuli suggest fundamental functional differences across classes of JAKi.