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

Table 3 Average daily percent STAT inhibition in CD4+ T cells, NK cells, and monocytes: baricitinib 4 mg

Stimulation/pSTAT	CD4+ T cells			NK cells			Monocytes
Stimulation/pSTAT	Bari 4 mg	Upa 15 mg 30 mg	Tofa 5 mg 10 mg	Bari 4 mg	Upa 15 mg 30 mg	Tofa 5 mg 10 mg	Bari 4 mg	Upa 15 mg 30 mg	Tofa 5 mg 10 mg
JAK1/3-dependent cytokines
IL-2/pSTAT5	44	60* 71***	78* 89*	34	36 48**	72* 85*	NS
IL-4/pSTAT6	30	45* 57***	69* 84*	52	61 71**	82* 91*	33	40 52**	51* 70*
IL-15/pSTAT5	36	47 59*	72* 85*	24	27 39**	62* 79*	NS
IL-21/pSTAT3	27	44* 55*	61* 76*	27	40* 52***	61* 76*	22	34 45*	46* 63**
JAK2/2- or JAK2/TYK2-dependent cytokines
IL-3/pSTAT5	NS			NS			47	52 61**	27*** 42
G-CSF/pSTAT3	NS			NS			25	17* 26	27 40**
GM-CSF/pSTAT5	NS			NS			45	55 65**	23* 37*
JAK1/JAK2/TYK2-dependent cytokines
IL-6/pSTAT3	29	22 33	39* 54***	NS			32	27 39	46* 61*
IL-10/pSTAT3	27	21 29	39* 53***	23	14* 21	34 48*	14	17 26*	25* 40*
IFN-γ/pSTAT1	NS			NS			37	34 46*	43 61*
IFN-α/pSTAT1	29	32 43*	24 36	25	21 31	23 37***	21	28 40***	21 32***
IFN-α/pSTAT3	45	48 61	40 55*	NS			62	72 81*	60 76*
IFN-α/pSTAT5	50	52 64	49 64**	NS			67	75 83*	62* 78**

Reported average daily percent STAT inhibition values are least squares estimates of mixed models as described in the “Statistical analysis” section. Protein binding was accounted for in the calculations. JAKis were administered once daily (baricitinib and upadacitinib) or twice daily (tofacitinib)
*p < 0.01, **p < 0.001, ***p < 0.0001 compared to baricitinib 4 mg
Bari baricitinib, G-CSF granulocyte colony-stimulating factor, GM-CSF granulocyte-macrophage colony-stimulating factor, IFN interferon, IL interleukin, JAK Janus kinase, JAKi JAK inhibitor, NK natural killer, NS no stimulation, pSTAT phosphorylated STAT, STAT signal transducer and activator of transcription, Tofa tofacitinib, TYK tyrosine kinase, Upa upadacitinib

ISSN: 1478-6362