Advances in pharmacotherapy for ulcerative colitis: a focus on JAK1 inhibitors

Figures & data

Table 1. Safety analysis data from Filgotinib studies. EAIR/100 PYE – Exposure-adjusted incidence rate per 100 patient-years of exposure, applies to DARWIN 3 only. AE, adverse events; SAE, serious adverse events; SI, serious infections; HZV, herpes zoster virus; VT, venous thrombosis; PE, pulmonary embolism; NMSC, non-melanoma skin cancer; Total, Total patients.

Ref	Study	Total	Groups	AE %	SAE %	SI %	HZV%	VT excl. PE %	PE %	Malignancy excl. NMSC %	NMSC %
[45] [46]	SELECTION	1348	FIL 100 mg	50.40%	5.00%	1.10%	0.20%	0%	0%	0.20%	0
	A and B		FIL 200 mg	53.60%	4.30%	0.60%	0.60%	0%	0.20%	0.20%	0.4%
	Induction studies		Placebo	56.30%	4.70%	1.10%	0.00%	0%	0%	0%	0,4%
[43]	SELECTION	664	Placebo responders	61.30%	4.30%	1.10%	0.00%	2,2%	0%	0%	0%
	Maintenance study		FIL 100 mg-to-placebo	65.90%	7.70%	2.20%	1.10%	0%	0%	0%	0%
			FIL 100 mg	60.30%	4.50%	1.70%	0.00%	0%	0%	0.60%	0.6%
			FIL 200 mg-to-placebo	59.60%	0.00%	0.00%	0.00%	0%	0%	0%	0%
			FIL 200 mg	66.80%	4.50%	1.00%	0.50%	0%	0%	0.50%	0%
[41]	TORTUGA	116	FIL 200 mg	31.00%	2.00%	2.00%	0.00%	2%	0%	0%	0%
			Placebo	31.00%	0.00%	0.00%	0.00%	0%	0%	0.00%	0%
[42]	EQUATOR	131	FIL 200 mg	57.00%	2.00%	2.00%	2.00%	0%	0%	0%	0%
			Placebo	59.00%	2.00%	0.00%	0.00%	0%	0%	0.00%	0%
[50]	DARWIN 1	594	Placebo	57.10%	7.10%	1.80%	1.80%	0%	0%	0.00%	0%
			Continued 50 mg x 1	52.40%	0.00%	0.00%	0.00%	0%	0%	0.00%	0%
			Continued 100 mg x1	43.50%	4.70%	3.50%	0.00%	0%	0%	0.00%	0%
			Continued 200 mg x1	58.10%	2.30%	1.20%	1.20%	0%	0%	0.00%	0%
			Continued 25 mg x2	53.60%	1.40%	0.00%	1.40%	0%	0%	0.00%	0%
			Continued 50 mg x2	54.10%	0.00%	0.00%	0.00%	0%	0%	0.00%	0%
			Continued 100 mg x2	53.60%	3.60%	1.20%	2.40%	0%	0%	0.00%	0%
			Placebo to 100 mg x1	46.70%	0.00%	0.00%	0.00%	0%	0%	0.00%	0%
			Placebo to 50 mg x2	46.70%	0.00%	0.00%	0.00%	0%	0%	0.00%	0%
			50 mg to 100 mg x1	47.40%	0.00%	0.00%	0.00%	0%	0%	0.00%	0%
			25 mg x2 to 50 mg x2	70.60%	5.90%	0.00%	0.00%	0%	0%	0.00%	0%
[51]	DARWIN 2	283	Placebo up to week 12	38.90%	1.40%	0.00%	0.00%	0%	0%	0.00%	0%
			FIL 50 mg up to week 12	40.30%	1.40%	1.40%	0.00%	0%	0%	0.00%	0%
			FIL 100 mg up to week 12	32.90%	0.00%	0.00%	0.00%	0%	0%	0.00%	0%
			FIL 200 mg up to week 12	43.50%	4.30%	1.40%	0.00%	0%	0%	0.00%	0%
			FIL 50 mg up to week 24	52.60%	3.50%	2.00%	2.00%	0%	0%	0.00%	0%
			FIL 100 mg up to week 24	44.30%	2.90%	1.00%	0.00%	0%	0%	0.00%	0%
			FIL 200 mg up to week 24	50.70%	4.30%	1.00%	0.00%	0%	0%	0.00%	0%
			Placebo to FIL 100 mg	15.40%	1.50%	1.50%	0.00%	0%	0%	0.00%	0%
			FIL 50 mg to FIL 100 mg	26.70%	0.00%	0.00%	0.00%	0%	0%	0.00%	0%
						EAIR/100 PYE
[43]	DARWIN 3	790	FIL + MTX	24.60%	3.10%	0.60%	1.30%	0,1%	0%	0.50%	0,3%
	Data up to week 204		FIL monotherapy	25.80%	4.30%	1.70%	1.50%	0%	0%	0.60%	0,1%
[44]	FITZROY	174	Placebo up to week 20	82.00%	14.00%	0.00%	0.00%	0%	0%	0.00%	0%
			Placebo to FIL 100 mg
			Placebo (week 0–10)	59.00%	0.00%	0.00%	0.00%	0%	0%	0.00%	0
			100 mg FIL (week 10–20)	50.00%	5.00%	0.00%	0.00%	0%	0%	0.00%	0
			FIL 200 mg to placebo
			FIL 200 (week 0–10)	74.00%	0.00%	0.00%	0.00%	0%	0%	0.00%	0
			Placebo (week 10–20)	61.00%	0.00%	0.00%	0.00%	0%	0%	0.00%	0
			FIl 200 mg to FIL 100 mg	80.00%	3.00%	0.00%	3.00%	0%	0%	0.00%	0
			FIL 200 mg up to week 20	81.00%	16.00%	5.00%	4.00%	0%	0%	0.00%	0

Table 2. Safety analysis data from upadacitinib studies. AE, adverse events; SAE, serious adverse events; SI, serious infections; HZV, herpes zoster virus; VT, venous thrombosis; PE, pulmonary embolism; NMSC, non-melanoma skin cancer; Total, Total patients.

Ref	Study	Total	Groups	AE %	SAE %	SI %	HZV%	VT, PE %	Malignancy excl. NMSC %	NMSC %
[56]	UC1	474	Placebo	62%	6%	1%	0%	0%	0%	0%
			Upadacitinib 45 mg QD	56%	6%	2%	<1%	0%	0%	0%
[56]	UC2	521	Placebo	40%	5%	1%	0%	1%	0%	0%
			Upadacitinib 45 mg QD	53%	3%	1%	1%	0%	0%	0%
[56]	UC3	451	Placebo	76%	13%	4%	0%	0%	<1%	0%
			Upadacitinib 15 mg QD	78%	7%	3%	4%	0%	<1%	0%
			Upadacitinib 30 mg QD	79%	6%	3%	4%	1%	1%	1%
[58]	CELEST
	Induction	220	Placebo	73%	5.40%	0%	0%	0%	0%	0%
			UPA 3 mg BID	87.20%	12.80%	7.70%	0%	0%	0%	0%
			UPA 6 mg BID	78.40%	5.40%	0%	0%	0%	0%	0%
			UPA 12 mg BID	80.60%	27.80%	8.30%	0%	0%	0%	0%
			UPA 24 mg BID	83.30%	8.30%	2.80%	2.8%	0%	0%	2.80%
			UPA 24 mg QD	82.90%	20%	5.70%	0%	0%	0%	0%
[58]	Maintenance	178	UPA 3 mg BID	75.00%	25.00%	8.30%	0%	0%	0%	0%
			UPA 6 mg BID	60.90%	8.70%	0.00%	0%	0%	0%	0%
			UPA 12 mg BID	72.90%	8.50%	1.70%	1.7%	0%	3.4%	0%
			UPA 24 mg QD	63.90%	11.10%	0.00%	2.8%	0%	0%	0%
[59]	NCT02925117	166	Placebo	63.00%	2.50%	0.00%	0%	0.00%	0%	0%
			UPA 7,5 mg QD	74.00%	4.80%	4.80%	0%	0.00%	0%	0%
			UPA 15 mg QD	76.00%	2.40%	2.40%	0%	0.00%	0%	0%
			UPA 30 mg QD	79.00%	0.00%	0.00%	0%	0.00%	0%	0%

Table 3. Safety analysis data from Ivarmacitinib studies. AE, adverse events; SAE, serious adverse events; SI, serious infections; HZV, herpes zoster virus; VT, venous thrombosis; PE, pulmonary embolism; Total, Total patients.

Ref	Study	Total	Groups	AE %	SAE %	SI %	HZV%	VT, PE %	Malignancy %
[60]	AMBER2
	Treatment phase	164	8 mg QD	43.90%	4.90%	2.40%	0%	0%	0%
			4 mg BID	48.80%	0%	0%	0%	0%	0%
			4 mg QD	48.80%	4.90%	2.40%	0%	0%	0%
			Placebo	39%	4.90%	2.40%	0%	0%	0%
[60]	Entire study	157	8 mg QD	57.70%	7.70%	3.80%	0%	0%	0%
			4 mg BID	62.70%	2%	2%	0%	0%	0%
			4 mg QD	53.70%	3.70%	1.90%	0%	0%	0%
[61]	NCT04162899	105	4 mg QD	60.00%	5.70%	0.00%	2,9%	0%	0%
			8 mg QD	68.60%	2.90%	0.00%	2,9%	0%	0%
			Placebo	51.40%	0.00%	0.00%	0%	0%	0%

Figure 1. Simplified JAK/STAT pathway. Cytokines and their associated receptors align with the downstream events depicted in the bottom.

Figure 2. Clinical remission from the induction phases, of the three JAK1 inhibitors discussed prior.

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