Efficacy and safety of peficitinib in rheumatoid arthritis

Figures & data

Figure 1. JAK family and their related cytokines. The binding of cytokines, growth factors, interferons, and peptide hormones to their respective receptors phosphorylates JAKs through the reciprocal interaction of two adjoining JAKs.

Table 1. JAK Inhibitors approved for RA (not direct comparison).

	Structure	Inhibitory activity
		JAK1	JAK2	JAK3	TYK2
Tofacitinib^a		15	77	55	489
Baricitinib^a		6	9	487	30
Peficitinib^b		4	5	0.7	5
Upadacitinib^c		47	120	2304	4690

^aAssays run in the presence of 1mM ATP [7].

^bAssays run at the K_m for ATP [8].

^cAssays rung in the presence of 0.1 mM ATP [9].

Figure 2. ACR50 achievement of placebo and each peficitinib dose in the five randomized, placebo-controlled trials. RA21 and RA22 were global phase 2b trials. RAJ1 and RAJ were conducted in Japan, and RAJ3 was conducted in Japan, Korea, and Taiwan. ACR, American College of Rheumatology. The approved peficitinib dose for rheumatoid arthritis in Japan was 100 mg and 150 mg daily.

Table 2. Summary of adverse events in the five randomized, placebo-controlled trials.

Adverse events	RA21		RA22		RAJ1*		RAJ3*				RAJ4*
	Placebo	Peficitinib	Placebo	Peficitinib	Placebo	Peficitinib	Placebo	Peficitinib	Peficitinib	Etanercept	Placebo	Peficitinib	Peficitinib
							(0–12 w)	(0–12 w)	(0–52 w)	(0–52 w)	(0–12 w)	(0–12 w)	(0–52 w)
	N = 72	N = 306	N = 51	N = 238	N = 56	N = 225	N = 101	N = 203	N = 203	N = 200	N = 174	N = 174	N = 348
Adverse events	34 (47.2)	146 (47.7)	22 (43.1)	99 (41.6)	36 (64.3)	144 (64.0)	54 (53.5)	114 (55.3)	181 (87.9)	178 (89.0)	84 (49.4)	193 (55.5)	307 (88.2)
Serious adverse events	0 (0)	3 (0.9)	2 (3.9)	10 (4.2)	1 (1.8)	6 (2.7)	4 (4.0)	5 (2.4)	15 (7.3)	18 (9.0)	4 (2.4)	8 (2.3)	32 (9.2)
Serious infection	0 (0)	2 (0.6)	0 (0)	1 (0.4)	0 (0)	0 (0)	0 (0)	NA	3 (1.5)	4 (2.0)	0 (0)	NA	12 (3.4)
Herpes zoster	0 (0)	3 (0.9)	1 (2.0)	1 (0.4)	0 (0)	4 (1.8)	0 (0)	NA	9 (4.4)	5 (2.5)	2 (1.7)	NA	19 (5.5)
Δwhite blood cell count (/µL)	100	−235	410	−143	NA	NA	NA	NA	NA	NA	NA	NA	NA
Δneutrophil count (/µL)	291	−121	298	−68	146	−223	−465	−522	−727	−1459	−41	−650	−718
Δlymphocyte count (/µL)	−190	−58	132	−26	57	−28	NA	NA	NA	NA	NA	NA	NA
Δhemoglobin (g/dL)	−0.08	0.078	−0.16	0.30	−0.52	0.03	−0.04	2.8	0.39	0.52	0.2	0.48	0.46
Δplatelet (10^9/L)	8	−7.9	7.6	−11.4	26.9	−13.5	1.8	−33.3	−35.2	−56.3	1.6	−44.8	−48.6
ΔCreatinine (mg/dL)	0	0.03	−0.03	0.04	−0.1 (µmol/L)	3.4 (µmol/L)	−2.5 (µmol/L)	4.7 (µmol/L)	6.4 (µmol/L)	4.2 (µmol/L)	−0.1 (µmol/L)	5.0 (µmol/L)	8.2 (µmol/L)
AST (>2xULN)	0	0	0	0	NA	NA	Δ 0.8 (U/L)	Δ 3.8 (U/L)	Δ 4.7 (U/L)	Δ 3.8 (U/L)	Δ −0.1 (U/L)	Δ 4.6 (U/L)	Δ 5.6 (U/L)
ALT(>2xULN)	0	0	0	3 (1.2)	1 (1.8)	2 (0.9)	Δ 2.0 (U/L)	Δ 4.6 (U/L)	Δ 4.9 (U/L)	Δ 4.6 (U/L)	Δ −1.7 (U/L)	Δ 5.4 (U/L)	Δ 5.4 (U/L)
ΔHDL cholesterol (mg/dL)	−2.2	5.1	1.6	3.1	−0.09 (mmol/L)	0.20 (mmol/L)	0.02 (mmol/L)	0.32 (mmol/L)	0.35 (mmol/L)	0.06 (mmol/L)	0.02 (mmol/L)	0.3 (mmol/L)	0.3 (mmol/L)
ΔLDL cholesterol (mg/dL)	1.5	0.4	1.2	1.8	−0.16 (mmol/L)	0.08 (mmol/L)	0.02 (mmol/L)	0.21 (mmol/L)	0.30 (mmol/L)	0.11 (mmol/L)	0.01 (mmol/L)	0.3 (mmol/L)	0.4 (mmol/L)
ΔCPK (U/L)	−7	28	−4	24	−5.6	30.0	0.6	61.6	97.1	86.4	−1.7	55.5	83.6
Thrombosis	NA	NA	NA	NA	NA	NA	0	0	0	0	0	0	0
Malignancies	0	0	0	0	0	0	0	NA	2 (0.9)	1 (0.5)	1 (0.6)	NA	1 (0.3)

The number (percentage) was expressed unless otherwise indicated. The pooled mean changes of all peficitinib groups from baseline were calculated from the values in each manuscript.

*Treatment emergent adverse event.

AST: aspartate transaminase; ULN: upper limit of normal; ALT: alanine transaminase; HDL: high-density lipoprotein; LDL: low density lipoprotein; CPK: creatine phosphokinase; NA: not available.

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