Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

Table 2 Meta-analyses of immune checkpoint inhibitor-mediated colitis and diarrhea with immune checkpoint inhibitor use

Meta-analysis	No. of studies	ICI targets	Malignancies	GI malignancy	Trial Phase	Diarrhea (incidence, %)					Colitis (incidence, %)
Ref.						Total	Anti-CTLA-4	Combo1	Anti-PD-1		Anti-PD-L1	Total	Anti-CTLA-4	Combo1	Anti-PD-1	Anti-PD-L1
Khoja et al[25], 2017	48	CTLA-4	Melanoma	Colorectal	1-3		30.2		12.1		7.3		5.7		0.7	0.0
		PD-1	Solid tumors	GEJ
		PD-L1		Liver
				Pancreas
Wang et al[29], 2017	34	CTLA-4	Melanoma	None	1-3		7.92	9.22	1.32		0.32	2.4	9.1	13.6	1.4	1.0
		Combination1	Solid tumors
		PD-1
		PD-L1
De Velasco et al[30], 2017	21	CTLA-4	Melanoma	None	2-3							2.3
		PD-1	Solid tumors
		PD-L1
Wang et al[33], 2017	46	PD-1	Melanoma	Colorectal	1-3	4-13						1.0
		PD-L1	Solid tumors	Gastric
			Hematologic
Zhang et al[31], 2018	11	CTLA-4	Melanoma	None	1-3		173	32.7	173				2.93	14.2	2.93
		Combination1	Sarcoma
		PD-1	Solid tumors
Tandon et al[27], 2018	18	CTLA-4	Melanoma	None	1-3		35.4	44.2	13.7				11.0	14.5	2.0
		Combination1
		PD-1
Baxi et al[32], 2018	13	PD-1	Melanoma	None	2-3							0.7			0.3-1.1	0.5
		PD-L1	Solid tumors
Komaki et al[28], 2018	22	CTLA-4	Melanoma	None	2-3		40.0		9.9	10.7			8.4		0.9
		PD-1	Solid tumors
		PD-L1
Bishay et al[34], 2020	27	Combination1	NSCLC	None	1-3			13.2-40.4	9.1	11.0				7.3-12.1	0.9	0.4
		PD-1
		PD-L1
Yang et al[35], 2020	10	CTLA-4	Melanoma	None	2-3		31.5		30.0	7.6			5.8		2.3
		PD-1	NSCLC
		PD-L1	Breast
Yao et al[36], 2020	40	CTLA-4	Melanoma	Colorectal	2-3								8.1	14.5	1.44	1.44
		Combination1	Solid tumors	Gastric/GEJ
		PD-1		HCC
		PD-L1

¹Combination anti-cytotoxic T-lymphocyte antigen 4 plus anti-programmed cell death protein-1.

²Grade 3-4 diarrhea only.

³Did not distinguish between monotherapy with ipilimumab or nivolumab.

⁴Combined incidence with programmed cell death protein-1 and programmed cell death-ligand 1.

ICI: Immune checkpoint inhibitor; IMC: Immune checkpoint inhibitor-mediated colitis and diarrhea; CTLA-4: Cytotoxic T-lymphocyte antigen 4; PD-1: Programmed cell death protein-1; PD-L1: Programmed cell death-ligand 1; GEJ: Gastroesophageal junction; NSCLC: Non-small cell lung cancer; HCC: Hepatocellular carcinoma.