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

Table 2 Hours per day above IC₅₀ 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	9	15.3* 20.6**	23.8* 24.2*	4.5	6.6 10.5**	21.4* 24.0*	NS
IL-4/pSTAT6	3.7	9.9 14.4**	19.6* 24.2*	12.6	17.5 22.3*	24.0* 24.0*	4.5	8.2 12.3**	12.3* 19.7*
IL-15/pSTAT5	5.5	10.4 14.5*	21.2* 24.0*	1	3.4 8.1**	17.0* 23.0*	NS
IL-21/pSTAT3	0.7	9.0* 13.1*	17.0* 23.6*	1.2	7.7 11.6*	17.5* 23.9*	0	4.4 8.6*	12.5* 18.9**
JAK2/2- or JAK2/TYK2-dependent cytokines
IL-3/pSTAT5	NS			NS			10.1	13.0 18.3**	0.3*** 8.1
G-CSF/pSTAT3	NS			NS			1.4	0.1 3.2	2.3 8.5*
GM-CSF/pSTAT5	NS			NS			9.2	12.6 18.1**	2.2*** 9.0
JAK1/JAK2/TYK2-dependent cytokines
IL-6/pSTAT3	1.9	0.6 5.5	7.3* 14.8***	NS			3.6	3.1 7.6*	10.8* 18.2***
IL-10/pSTAT3	1.2	0 2.8	7.6* 15.1***	0.4	0 0.5	4.2* 11.8***	0	0.6 3.5	0.8 7.8***
IFN-γ/pSTAT1	NS			NS			6	5.8 9.7*	9.4 16.8*
IFN-α/pSTAT1	0.9	3.6 8.1**	0 5.2	0.2	0 4.8**	0.1 5.7***	0	2.9 7.5***	0 2.8***
IFN-α/pSTAT3	9.6	10.4 15.0	8.0 15.5***	NS			18.2	21.7 23.7	16.6 23.2*
IFN-α/pSTAT5	12	12.9 17.2	12.2 19.6***	NS			19.8	21.9 23.5	17.2* 23.9**

Reported hours per day above IC₅₀ 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, IC₅₀ half maximum inhibitory concentration, IFN interferon, IL interleukin, JAK Janus kinase, JAKi JAK inhibitor, NK natural killer, NS no stimulation, pSTAT phosphorylated signal transducer and activator of transcription, Tofa tofacitinib, TYK tyrosine kinase, Upa upadacitinib

ISSN: 1478-6362