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Supplemental Figure 1. Evaluation of concurrent hsCRP elevation in patients with and without peripheral blood eosinophilia by IBD type.

Supplemental Figure 2. Time to event analysis by presence of peripheral blood

eosinophilia and concurrent elevated high sensitivity C-reactive protein (hsCRP) (n= 98) compared to patients with only hsCRP elevation (n=303). A) Hospitalization in CD. B) Hospitalization in UC. C) Surgical resection in CD. D) Colectomy in UC.

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Supplemental Table 1. Peripheral blood eosinophilia patterns by IBD type. a

CD (n=171)

UC (n=182) Degree of Eosinophilia

Mild Moderate Severe Unknown

166 (97.1) 5 (2.9)

0 0

171 (94.0) 6 (3.3)

0 5 (2.7)

0.25

Recurrent Eosinophilia 82 (48.0) 94 (51.6) 0.41

a Disease type missing on 106 patients

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Supplemental Table 2. Six-year patterns of healthcare utilization, disease activity, and IBD medication use by presence of peripheral blood eosinophilia without comorbid PSC patients

PBE (n=376)

No PBE (n=1698) CD

(n=162)

UC (n=160)

CD (n=949)

UC (n=517)

p-value

Healthcare Utilization

ED, % 100

(61.7)

96 (60.0) 441 (46.5)# 222 (42.9)#

<0.0001

Hospitalization, % 114 (70.4)

93 (58.1) 442 (46.6)# 177 (34.2)#

<0.0001

IBD-Surgery, % 85 (52.5) 39 (24.4) 298 (31.4)# 62 (12.0)# <0.0001 Disease Activity and Quality of Life

HB-CD, median (IQR)

UCAI, median (IQR)

4.6 (5.6) --

-- 3.7 (4.6)

3 (4.7)#

--

-- 2.0 (4.5)#

<0.0001

<0.0001

hsCRP, % 108

(66.7)

102 (63.8)

415 (43.7)# 185 (35.8)#

<0.0001

ESR, % 84 (51.9) 82 (51.3) 300 (31.6)# 148

(28.6)#

<0.0001

SIBDQ, median (IQR)

49.5 (18) 50.9 (14.8)

52.9 (16.9)#

56.8 (13.6)#

<0.0001

IBD Medications

Prednisone, % 104

(64.2)

121 (75.6)

434 (45.7)# 261 (50.5)#

<0.0001

Biologic, % aTNF Othera

109 (67.3) 4 (2.5)

60 (37.5) 1 (0.6)

453 (47.7)#

5 (0.5)#

107 (20.7)#

2 (0.4)^

<0.0001 0.21

IM, % 94 (58.0) 84 (52.5) 573 (60.4)^ 193

(37.3)#

0.21

5-ASA, % 53 (32.7) 109 297 (31.3)^ 312 (60.3)^ 0.004

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(68.1) Enteric Steroidsb,

%

41 (25.3) 11 (6.9) 175 (18.4)^ 37 (7.2)^ 0.58

Financial Charges Total Charges (USD), median (IQR)

$118,171 (307,115)

$66,576 (14,531)

$29,673 (131,694)#

$52,032 (192,226)#

<0.0001

a Natalizumab, vedolizumab, golimumab, rituximab

Statistical comparisons reported between PBE and No PBE groups. Disease specific statistical comparisons denoted by superscript symbols in No PBE columns.

b Oral budesonide, per rectum corticosteroid preparations

# p<0.05

^ p=NS

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Supplementary Table 3. Univariate logistic regression modeling in both CD and UC for outcomes of hospitalization and IBD-related surgery.

Crohn’s Disease Ulcerative Colitis Hospitalizatio

n

p-value

Surgery

p-value

Hospitalizatio n

p-value

Surgery

p-value

PBE <0.0001 0.74 <0.0001 <0.0001

CRP <0.0001 <0.001 <0.0001 0.001

Age 0.171 0.29 0.019 0.776

Sex 0.128 0.70 0.922 0.383

BMI 0.997 <0.001 0.332 0.291

Psych 0.017 0.51 0.025 0.185

Asthma 0.548 0.45 0.089 0.431

Allergies 0.01 0.51 0.068 0.102

Med Allergies 0.002 0.47 0.035 0.018

Prior Surgery 0.002 0.45 0.001 <0.0001

Location 0.867 0.003 -- --

Behavior 0.074 <0.001 -- --

Perianal 0.508 0.89 -- --

Extent -- -- 0.017 0.015

Disease Duration 0.148 0.02 0.105 0.577

aTNF 0.001 <0.001 0.013 0.035

Steroids <0.0001 <0.001 <0.0001 0.045

IMs 0.004 <0.001 0.995 0.841

Smoking 0.01 0.90 0.05 .10

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Narcotics <0.0001 <0.0001 <0.0001 <0.0001 Adrenal

Insufficiency

-- * 0.04 -- * -- *

Sjogren’s 0.55 0.52 0.467 -- *

Lupus 0.77 0.65 -- ** -- **

Systemic Sclerosis -- ** -- ** -- ** -- **

Rheumatoid Arthritis

0.37 0.80 0.75 0.08

PBE: peripheral blood eosinophilia; CRP: C-reactive protein; BMI: body mass index;

aTNF: anti-tumor necrosis factor; IM: immunomodulator

* Covariate excluded from model due to perfect outcome prediction

** Covariate excluded from model due to collinearity

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Supplementary Table 4. Spearman rank-order correlation of number of years with

peripheral blood eosinophilia (range 0-6) and rates of healthcare utilization, disease activity scores, elevated inflammatory biomarker rates, quality of life metrics, and total financial charges.

CD

(n=1,148)

UC

(n=725)

Spearman’s rho p-value Spearman’s rho p-value No.

Hospitalization s

0.82 <0.00001 0.72 <0.00001

No. ED Visits 0.21 <0.00001 0.21 0.0001

No. IBD- Surgeries

0.17 <0.00001 0.13 0.0004

HBI 0.12 0.0001 -- --

UCAI -- -- 0.19 <0.00001

Years with hsCRP Elevation

0.19 <0.00001 0.30 <0.00001

Years with ESR

Elevation 0.19 <0.00001 0.21 <0.00001

SIBDQ -0.09 0.005 -0.16 0.0001

Total Charges

(USD) 0.21 <0.00001 0.27 <0.00001

CD: Crohn’s disease; UC: ulcerative colitis; ED: emergency department; IBD:

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inflammatory bowel disease; HBI: Harvey-Bradshaw Index; UCAI: ulcerative colitis activity index; SIBDQ: short inflammatory bowel disease questionnaire; hsCRP: high- sensitivity C-reactive protein; ESR: erythrocyte sedimentation rate; USD: United States dollar

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