Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations

Table 1 IC₅₀ values in CD4+ T cells, NK cells, and monocytes

Stimulation/pSTAT	CD4+ T cells			NK cells			Monocytes
Stimulation/pSTAT	Bari (nM)	Upa (nM)	Tofa (nM)	Bari (nM)	Upa (nM)	Tofa (nM)	Bari (nM)	Upa (nM)	Tofa (nM)
JAK1/3-dependent cytokines
IL-2/pSTAT5	29	10**	11***	44	27*	15***	NS
IL-4/pSTAT6	48	18***	18***	22	8*	8***	45	22**	35*
IL-15/pSTAT5	40	17***	15***	67	40*	22***	NS
IL-21/pSTAT3	64	20***	22***	62	24**	21***	85	34	37
JAK2/2- or JAK2/TYK2-dependent cytokines
IL-3/pSTAT5	NS			NS			26	12*	102***
G-CSF/pSTAT3	NS			NS			65	84	97**
GM-CSF/pSTAT5	NS			NS			30	13***	97***
JAK1/JAK2/TYK2-dependent cytokines
IL-6/pSTAT3	61	58	56	NS			48	43	40
IL-10/pSTAT3	68	87	55	87	124	74	142	80***	104*
IFN-γ/pSTAT1	NS			NS			38	30	46***
IFN-α/pSTAT1	64	40	132***	76	69	121***	97	44**	163***
IFN-α/pSTAT3	27	17	51***	NS			14	6*	23***
IFN-α/pSTAT5	23	14	36**	NS			13	5**	22***

Reported IC₅₀ values are least squares estimates of mixed models as described in the “Statistical analysis” section. For G-CSF, IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-15, and IL-21, reported IC₅₀ values are based on two batches of data amounting to 12 donors for baricitinib and 6 donors for upadacitinib and tofacitinib; for GM-CSF, IFN-α, and IL-3, reported IC₅₀ values are based on three batches of data amounting to 10 donors for baricitinib, 6 donors for upadacitinib, and 4 donors for tofacitinib. The primary pSTAT observed for each stimulus is reported in the table. Protein binding was not accounted for in the IC₅₀ calculations
*p < 0.01, **p < 0.001, ***p < 0.0001 compared to baricitinib
Bari baricitinib, G-CSF granulocyte colony-stimulating factor, GM-CSF granulocyte-macrophage colony-stimulating factor, IC₅₀ half maximum inhibitory concentration, IFN interferon, IL interleukin, JAK Janus kinase, NK natural killer, NS no stimulation, pSTAT phosphorylated signal transducer and activator of transcription, Tofa tofacitinib, TYK tyrosine kinase, Upa upadacitinib

ISSN: 1478-6362