Disease exacerbation is common in inflammatory bowel disease patients treated with immune checkpoint inhibitors for malignancy

doi:10.12998/wjcc.v10.i6.1787

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 10, Issue 6

This Article

Academic Content and Language Evaluation of This Article

Academic Rules and Norms of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (4891)

All Articles published online

The chart showing PDF series, WORD series, HTML series, Tables (1-3) series.

Item

Count

PDF

230

WORD

128

HTML

2330

Tables (1-3)

262

Sum=2950

Featured Article

The chart showing Browse series, Download series.

Item

Count

Browse

194

Download

522

Sum=716

Publishing Process of This Article

Item

Count

Browse

331

Download

894

Sum=1225

Feb 26, 2022 (publication date) through Jul 22, 2024

Times Cited of This Article

Times Cited (7)

Journal Information of This Article

Publication Name

World Journal of Clinical Cases

ISSN

2307-8960

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Clin Cases. Feb 26, 2022; 10(6): 1787-1794
Published online Feb 26, 2022. doi: 10.12998/wjcc.v10.i6.1787

Table 1 Baseline demographics and inflammatory bowel disease characteristics stratified by inflammatory bowel disease diagnosis

	Crohn's disease	Ulcerative colitis	Indeterminate IBD
	n = 4	n = 14	n = 1
Demographics
Age at first ICI use, yr, median, IQR	63, 4	69, 12.5	60, 0
Female sex, n (%)	2 (50.0)	2 (14.3)	0 (0)
White race, n (%)	3 (75.0)	11 (78.6)	1 (100)
Black race, n (%)	1 (25.0)	1 (7.1)	0 (0)
Asian race, n (%)	0 (0)	1 (7.1)	0 (0)
Other race, n (%)	0 (0)	1 (7.1)	0 (0)
Non-Hispanic ethnicity, n (%)	4 (100)	12 (85.7)	1 (100)
Hispanic/Latino ethnicity, n (%)	0 (0)	2 (14.3)	0 (0)
Never smoker, n (%)	2 (50.0)	5 (35.7)	0 (0)
Former smoker, n (%)	2 (50.0)	9 (64.3)	1 (100)
Body mass index, median, IQR	21.6, 1.7	25.5, 6.1	24.1, 0
IBD characteristics
Age at IBD onset, yr, median, IQR¹	56, 0	39.5, 32.8	54, 0
IBD duration, yr, median, IQR¹	7, 1	20, 29.25	6, 0
Disease location, n (%)	L1: 1 (25.0)	E1: 1 (7.1)	-
	L2: 1 (25.0)	E2: 4 (28.6)	-
	L3: 2 (50.0)	E3: 7 (50.0)	-
	-	Unknown: 2 (14.3)	-
Disease behavior, n (%)	B1: 2 (50.0)	-	-
	B2: 1 (25.0)	-	-
	B3: 0 (0)	-	-
	Unknown: 1 (25.0)	-	-
Perianal disease, n (%)	0 (0)	-	-
Extra-intestinal manifestations, n (%)	0 (0)	0 (0)	0 (0)

¹Unknown for 2 CD and 4 UC patients because date of IBD onset was not available.

Disease location and behavior were categorized using the Montreal classification: Location (L): L1, ileal disease; L2, colonic disease; L3, ileocolonic disease; Behavior (B): B1, inflammatory phenotype; B2, obstructive/stricturing phenotype; B3, penetrating/fistulizing phenotype; Extent (E): E1, proctitis; E2, left-sided colitis; E3, extensive/pan colitis. IQR: Interquartile range; IBD: Inflammatory bowel disease; ICI: Immune checkpoint inhibitor.

Table 2 All baseline clinical characteristics stratified by prevalence of inflammatory bowel disease exacerbation

	Exacerbation	No exacerbation	P value¹
	n = 7	n = 12	P value¹
Demographics
Female sex, n (%)	0 (0)	4 (33.3)	0.2451
Age at first ICI use, yr, median, IQR	60, 12.5	66, 9.3	0.6055
White race, n (%)	4 (57.1)	11 (91.7)	0.1174
Black race, n (%)	1 (14.3)	1 (8.3)	1.0000
Asian race, n (%)	1 (14.3)	0 (0)	0.3684
Other race, n (%)	1 (14.3)	0 (0)	0.3684
Non-Hispanic ethnicity, n (%)	5 (71.4)	12 (100)	0.1228
Hispanic/Latino ethnicity, n (%)	2 (28.6)	0 (0)	0.1228
Former smoker, n (%)	3 (42.9)	9 (75.0)	0.3261
Body mass index, median, IQR	24.3, 1.8	25.2 (6.7)	0.9018
Co-morbidities
Hypertension, n (%)	1 (14.3)	6 (50.0)	0.1733
Hyperlipidemia, n (%)	3 (42.9)	6 (50.0)	1.0000
Heart failure, n (%)	0 (0)	3 (25.0)	0.2632
Coronary artery disease, n (%)	0 (0)	2 (16.7)	0.5088
Chronic kidney disease, n (%)	0 (0)	2 (16.7)	0.5088
Diabetes mellitus, n (%)	2 (28.6)	1 (8.3)	0.5232
Gastroesophageal reflux disease, n (%)	1 (14.3)	1 (8.3)	1.0000
Asthma, n (%)	0 (0)	2 (16.7)	0.5088
Chronic obstructive pulmonary disease, n (%)	1 (14.3)	1 (8.3)	1.0000
IBD characteristics
Crohn's disease, n (%)	0 (0)	4 (33.3)	0.2451
Ulcerative colitis, n (%)	6 (85.7)	8 (66.7)	0.6027
Indeterminate IBD, n (%)	1 (14.3)	0 (0)	0.3684
Age at IBD onset, yr, median, IQR²	47, 28.3	56, 24.5	0.9668
IBD duration, yr, median, IQR²	11.5, 19.75	20, 24	0.9184
History of GI surgery before ICI use, n (%)	2 (28.6)	5 (41.7)	0.6562
Latest known disease state before ICI use, n (%)	Active: 0 (0)	Active: 0 (0)	1.0000
	Inactive: 5 (71.4)	Inactive: 10 (83.3)	0.6027
	Unknown: 2 (28.6)	Unknown: 2 (16.7)	0.6027
Latest available 25 (OH) D before ICI use, ng/mL, median, IQR³	38.9, 11.2	29.0, 9.5	0.8857
GI medications at start of ICI use, n (%)
Aminosalicylate	3 (42.9)	3 (25.0)	0.6169
Glucocorticoid	1 (14.3)	2 (16.7)	1.0000
Cholecalciferol (vitamin D3)	3 (42.9)	3 (25.0)	0.6169
Laxative (PEG, senna glycoside, docusate)	3 (42.9)	3 (25.0)	0.6169
Anti-diarrheal (diphenoxylate-atropine, loperamide)	1 (14.3)	3 (25.0)	1.0000
TNF inhibitor	0 (0)	1 (8.3)	1.0000
Mercaptopurine	1 (14.3)	0 (0)	0.3684
Other medications at start of ICI use, n (%)
Oral antibiotics	0 (0)	2 (16.7)	0.5088
Proton pump inhibitor	3 (42.9)	2 (16.7)	0.3047
Famotidine	0 (0)	2 (16.7)	0.5088
Metformin	1 (14.3)	0 (0)	0.3684
Insulin secretagogue	0 (0)	1 (8.3)	1.0000
Insulin	1 (14.3)	1 (8.3)	1.0000
Benzodiazepine	2 (28.6)	4 (33.3)	1.0000
Selective serotonin reuptake inhibitors	1 (14.3)	2 (16.7)	1.0000
Diuretic	0 (0)	4 (33.3)	0.2451
ACE inhibitor or angiotensin receptor blocker	3 (42.9)	5 (41.7)	1.0000
HMA-CoA reductase inhibitor	4 (57.1)	6 (50.0)	1.0000
Anticoagulant or antiplatelet	1 (14.3)	4 (33.3)	0.6027
Nonsteroidal anti-inflammatory drug	3 (42.9)	3 (25.0)	0.6169
Donezepil	1 (14.3)	1 (8.3)	1.0000
Glucosamine	1 (14.3)	1 (8.3)	1.0000
Ondansetron	2 (28.6)	3 (25.0)	1.0000
Chemotherapeutic kinase inhibitor	1 (14.3)	0 (0)	0.3684
Cancer characteristics and management
Primary cancer origin, n (%)
Bladder	0 (0)	5 (41.7)	0.1060
Melanoma	3 (42.9)	2 (16.7)	0.3047
Lung	2 (28.6)	4 (33.3)	1.0000
GI	1 (14.3)	1 (8.3)	1.0000
Other	1 (14.3)	3 (25.0)	1.0000
Radiation therapy for cancer, n (%)	5 (71.4)	9 (75.0)	1.0000
Checkpoint inhibitor, n (%)
Ipilimumab	2 (28.6)	1 (8.3)	0.5232
Nivolumab	2 (28.6)	2 (16.7)	0.6027
Pembrolizumab	4 (57.1)	8 (66.7)	1.0000
Atezolizumab	0 (0)	1 (8.3)	1.0000
Avelumab	0 (0)	0 (0)	1.0000
Durvalumab	0 (0)	1 (8.3)	1.0000
Cemiplimab	0 (0)	0 (0)	1.0000
Any anti-PD-1 or -PD-L1	6 (85.7)	12 (100)	0.3684
Combination anti-CTLA-4 and -PD-1/PD-L1	1 (14.3)	1 (8.3)	1.0000

¹P-values from Fisher's exact test for categorical variables or Mann-Whitney U test for continuous variables.

²Unknown for 1 patient with and 5 patients without immune checkpoint inhibitor (ICI)-attributed inflammatory bowel disease (IBD) exacerbations because date of IBD onset was not available.

³Unknown for 3 patients with and 8 patients without ICI-attributed IBD exacerbations.

IQR: Interquartile range; IBD: Inflammatory bowel disease; ICI: Immune checkpoint inhibitor; GI: Gastrointestinal; PEG: Polyethylene glycol; ACE: Angiotensin converting enzyme; HMA-CoA: Hydroxymethylglutaryl-coenzyme A; PD-1: Programmed cell death protein 1; PD-L1: Programmed death-ligand 1; CTLA-4: Cytotoxic T-lymphocyte antigen 4.

Table 3 Inflammatory bowel disease management and clinical outcomes following immune checkpoint inhibitor treatment stratified by prevalence of inflammatory bowel disease exacerbation

	Exacerbation	No exacerbation	P value¹
	n = 7	n = 12	P value¹
Follow up time, d, median, IQR	435, 306	572, 450	0.4824
Length of ICI use, mo, median, IQR	12, 10	6.5, 9.3	0.3685
Reason for ICI discontinuation, n (%)
Cancer remission	1 (14.3)	1 (8.3)	1.0000
Cancer non-response	0 (0)	2 (16.7)	0.5088
Side effect(s)	1 (14.3)	3 (25.0)	1.0000
Patient preference	0 (0)	1 (8.3)	1.0000
Deceased	1 (14.3)	2 (16.7)	1.0000
Unknown	0 (0)	1 (8.3)	1.0000
Not discontinued	4 (57.1)	2 (16.7)	0.1287
GI-related hospitalization, n (%)	4 (57.1)	0 (0)	0.0090
GI-related surgery, n (%)	2 (28.6)	0 (0)	0.1228
IBD medications used after ICI initiation, n (%)
Aminosalicylates	4 (57.1)	4 (33.3)	0.3765
Glucocorticoids	3 (42.9)	4 (33.3)	1.0000
TNF inhibitor	2 (28.6)	1 (8.3)	0.5232
Mercaptopurine	1 (14.3)	0 (0)	0.3684
None	2 (28.6)	5 (41.7)	0.6562
Deceased, n (%)	1 (14.3)	4 (33.3)	0.6027

¹P-values from Fisher's exact test.

IQR: Interquartile range; IBD: Inflammatory bowel disease; ICI: Immune checkpoint inhibitor; GI: Gastrointestinal; TNF: Tumor necrosis factor.

Citation: Rubin SJS, Balabanis T, Gubatan J, Habtezion A. Disease exacerbation is common in inflammatory bowel disease patients treated with immune checkpoint inhibitors for malignancy. World J Clin Cases 2022; 10(6): 1787-1794
URL: https://www.wjgnet.com/2307-8960/full/v10/i6/1787.htm
DOI: https://dx.doi.org/10.12998/wjcc.v10.i6.1787