Poor Patient-Reported Outcomes and Impaired Work Productivity in Patients With Inflammatory Bowel Disease in Remission

Abstract

Background & Aims
To evaluate associations between disease severity, patient-reported outcomes (PROs), and work productivity in patients with inflammatory bowel disease (IBD [Crohn disease [CD] and ulcerative colitis [UC]).

Methods
Patients diagnosed with CD or UC enrolled in CorEvitas’ IBD Registry (05/2017–09/2019) were included (N=1543; CD, n=812; UC, n=731). Disease severity was assessed using the Harvey-Bradshaw Index (CD) and partial Mayo Score (UC); psychosocial PROs (PROMIS [Patient-Reported Outcomes Measurement Information System]) and work productivity (WPAI [Work Productivity and Activity Impairment]) were assessed. Univariable and multivariable regression analyses assessed associations between PROs and disease severity.

Results
Among CD patients, 67.4% were in remission, 19.2% had mild disease, and 13.4% had moderate/severe disease; among UC patients, 52.7% were in remission, 35.3% had mild disease, and 12.0% had moderate/severe disease. For CD patients in remission, unadjusted percentages of patients with PROMIS scores outside normal limits ranged from 18.9% (depression) to 34.9% (fatigue). For CD patients in remission, 54.3% reported work productivity loss and 57.1% reported activity impairment. The unadjusted percentage of UC patients in remission with scores outside normal limits ranged from 15.7% (depression) to 28.7% (fatigue) for PROMIS and 10.5% (absenteeism) to 43.5% (activity impairment) for WPAI. Impairment increased with IBD severity. Congruently, adjusted estimates showed significant impairment in PROMIS and WPAI scores for CD and UC patients in remission.

Conclusions
In this real-world analysis, IBD patients across the spectrum of activity, from remission to severe disease, experienced impaired psychosocial function and reduced work productivity. Impairment, even among patients in remission, indicates an unmet need in this patient population.

Full text

ORIGINAL RESEARCH—CLINICAL
Poor Patient-Reported Outcomes and Impaired Work
Productivity in Patients With Inflammatory Bowel
Disease in Remission
Raymond K. Cross,
1
Jenny S. Sauk,
2
Joe Zhuo,
3
Ryan W. Harrison,
4
Samantha J. Kerti,
4
Kelechi Emeanuru,
4
Jacqueline O’Brien,
4
Harris A. Ahmad,
3
Antoine G. Sreih,
3
Joehl Nguyen,
5
Sara N. Horst,
6
and David Hudesman
7
1
Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore,
Maryland;
2
UCLA Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, Ronald Reagan UCLA
Medical Center, Los Angeles, California;
3
Bristol Myers Squibb, Princeton, New Jersey;
4
Departments of Biostatistics and
Epidemiology and Outcomes Research, CorEvitas, LLC (formerly known as Corrona, LLC), Waltham, Massachusetts;
5
Division
of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of North Carolina Eshleman School of
Pharmacy, Chapel Hill, North Carolina;
6
Division of Gastroenterology & Hepatology Clinical Services, Department of Medicine,
Vanderbilt University Medical Center, Nashville, Tennessee; and
7
New York University, Langone Health, New York, New York
BACKGROUND AND AIMS: This study aimed to evaluate as-
sociations between disease severity, patient-reported out-
comes (PROs), and work productivity in patients with
inflammatory bowel disease (IBD [Crohn’s disease (CD) and
ulcerative colitis (UC)]). METHODS: Patients diagnosed with
CD or UC enrolled in CorEvitas’IBDRegistry(May2017to
September 2019) were included (N ¼1543; CD, n ¼812;
UC, n ¼731). Disease severity was assessed using the
Harvey-Bradshaw Index (CD) and partial Mayo Score (UC);
psychosocial PROs (Patient-Reported Outcomes Measure-
ment Information System [PROMIS]) and work productivity
(Work Productivity and Activity Impairment [WPAI]) were
assessed. Univariable and multivariable regression analyses
assessed associations between PROs and disease severity.
RESULTS: Among CD patients, 67.4% were in remission,
19.2% had mild disease, and 13.4% had moderate/severe
disease; among UC patients, 52.7% were in remission, 35.3%
had mild disease, and 12.0% had moderate/severe disease.
For CD patients in remission, unadjusted percentages of pa-
tients with PROMIS scores outside normal limits ranged from
18.9% (depression) to 34.9% (fatigue). For CD patients in
remission, 54.3% reported work productivity loss, and 57.1%
reported activity impairment. The unadjusted percentage of
UC patients in remission with scores outside normal limits
ranged from 15.7% (depression) to 28.7% (fatigue) for
PROMIS and 10.5% (absenteeism) to 43.5% (activity impair-
ment) for WPAI. Impairment increased with IBD severity.
Congruently, adjusted estimates showed significant impair-
ment in PROMIS and WPAI scores for CD and UC patients in
remission. CONCLUSION: In this real-world analysis, IBD pa-
tients across the spectrum of activity, from remission to severe
disease, experienced impaired psychosocial function and
reduced work productivity. Impairment, even among patients in
remission, indicates an unmet need in this patient population.
Keywords: Crohn’s Disease; Ulcerative Colitis; Registry; Real-
World
Introduction
Crohn’s disease (CD) and ulcerative colitis (UC) are
chronic inflammatory diseases of the gastrointes-
tinal tract with periods of exacerbations and remissions.
Inflammatory bowel disease (IBD) is characterized by in-
testinal inflammation, extraintestinal manifestations, and
significant morbidity.
1–4
In North America, the estimated
incidence is up to 20.2 cases per 100,000 person-years for
CD and up to 19.2 cases per 100,000 person-years for
UC.
5
In a large IBD epidemiology study based on 12 million
US health insurance claims, the prevalence of CD and UC
among adults was estimated to be 241 and 263 per
100,000, respectively.
6
IBD treatment strategies seek to
induce and maintain remission, promote mucosal healing,
prevent complications, minimize the impact of comorbid-
ities, reduce the need for hospitalization and surgery, and
enhance the quality of life (QOL).
2,7
Several physician-reported indices of disease activity or
severity have been developed for the clinical assessment of
patients with IBD, including the Harvey-Bradshaw Index for
patients with CD and the partial Mayo Score for patients
with UC.
8
However, elements of a patient’s experience may
be underrepresented by these indices; specifically, fatigue is
highly prevalent in patients with IBD, has a negative impact
Abbreviations used in this paper: CD, Crohn’s disease; IBD, inflammatory
bowel disease; JAK, Janus kinase; OR, odds ratio; PROMIS, Patient-Re-
ported Outcomes Measurement Information System; PROs, patient-re-
ported outcomes; QOL, quality of life; SD, standard deviation; UC,
ulcerative colitis; WPAI, Work Productivity and Activity Impairment.
Most current article
Copyright © 2022 The Authors . Published by Elsevier Inc. on behalf of the
AGA Institute. This is an open access artic le under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc -nd/4.0/).
2772-5723
https://doi.org/10.1016/j.gastha.2022.07.003
Gastro Hep Advances 2022;1:927–935

on other patient-reported outcomes (PROs), and contributes
to poor health-related QOL.
9,10
In addition, compared with
the general population, patients with IBD have higher rates
of psychological comorbidities, such as depression and
anxiety,
11,12
reducing patients’QOL. The Patient-Reported
Outcomes Measurement Information System (PROMIS)
and the Work Productivity and Activity Impairment (WPAI)
questionnaires are validated assessments that measure the
impact of IBD on other symptoms, work productivity, and
activity impairment.
3,13
There is limited real-world evidence describing the as-
sociation between remission, disease severity, PROs, and
work productivity measures among IBD patients.
13,14
Data
from a US internet-based cohort found evidence of elevated
depression, anxiety, fatigue, sleep disturbance, and pain
interference reported on the PROMIS questionnaire in IBD
patients, relative to the general population. Over time,
PROMIS scores improved when disease activity improved
and worsened when disease activity was exacerbated.
13
Other studies have shown depression and/or anxiety may
be associated with clinical recurrence in IBD.
2,11,15
Addi-
tional studies have reported that active disease is associated
with worse WPAI scores in CD and UC patients.
16–18
To our
knowledge, there have been very few studies investigating
psychosocial PROs, specifically in patients with IBD in
remission, and there are currently limited data quantifying
the relationship between disease activity and both the WPAI
and PROMIS measures.
The objective of this study was to evaluate the associa-
tions between disease severity, psychosocial PROs, and
work productivity in patients with IBD from CorEvitas’IBD
Registry, which offers a unique source of real-world data for
patients with CD and UC.
Materials and Methods
Data Source and Study Design
Launched in May 2017, the IBD registry collects longitudinal
follow-up data from gastroenterologists and patients at the time
of outpatient clinical encounters using questionnaires. These
questionnaires collect data on demographics, disease duration,
medical history (including prior and current treatments for IBD),
disease activity, and PROs. As of June 2020, the Registry included
62 private and academic clinical sites with 135 gastroenterolo-
gists throughout 20 states in the United States.
This large, noninterventional, geographically diverse, cross-
sectional study of patients diagnosed with CD or UC who were
seen in a clinical practice setting and enrolled in CorEvitas’IBD
registry included visits from the IBD registry launch date of
May 3, 2017, to September 3, 2019.
Study Population
Registry Patient Selection. Included patients must
be aged 18 years; willing and able to provide written consent
for participation in the CorEvitas IBD registry and provide
personally identifiable information to include (at a minimum)
full name, date of birth, sex, and home address ZIP code; and
have been diagnosed with CD or UC by a gastroenterologist.
Patients enrolled on or after January 2019 have initiated or
switched to an approved biologic or Janus kinase (JAK) inhib-
itor for the treatment of CD or UC at enrollment or within 12
months before the enrollment visit.
Eligible medications for enrollment include the Food and
Drug Administration–approved biologic treatments for IBD
(tumor necrosis factor inhibitors: adalimumab and its bio-
similar, certolizumab, golimumab, and infliximab and its bio-
similar; interleukin-12/23 inhibitor: ustekinumab; integrin
a4b7 inhibitor: vedolizumab; integrin a4 inhibitor: natalizu-
mab; JAK inhibitor: tofacitinib).
Effective January 2019, therefore, enrollment of new pa-
tients on or initiating or switching to immunosuppressant
therapies (methotrexate, 6 mercaptopurine, azathioprine,
tacrolimus, cyclosporine, other immunosuppressants), 5-amino
salicylic agents, antibiotics, or steroids is on a temporary hold.
However, patients previously enrolled will continue to be fol-
lowed in the IBD registry.
Patients were excluded if they were participating or were
planning to participate in an interventional clinical trial with a
nonmarketed or marketed investigational drug (ie, phase I–IV
drug trial).
All participating investigators were required to obtain full
board approval for conducting research involving human sub-
jects. Sponsor approval and continuing review were obtained
through a central institutional review board (IRB; IntegReview,
protocol number is Corrona-PSO-500). For academic investi-
gative sites that did not receive a waiver to use the central IRB,
approval was obtained from the respective governing IRBs, and
documentation of approval was submitted to the sponsor
before initiating any study procedures. All registry subjects
were required to provide written informed consent before
participating.
Analysis Cohort Patient Selection. Inclusion/
exclusion criteria matched those for IBD registry enrollment.
Eligible patients were aged 18 years, diagnosed with CD or
UC, and enrolled in the IBD registry. Patients diagnosed with
indeterminate colitis or whose diagnosis changed at subse-
quent follow-up visits were excluded.
Patients were subsequently classified into 1 of 3 disease
severity groups (remission, mild disease, moderate/severe
disease) using the Harvey-Bradshaw Index for patients with CD
and the partial Mayo Score for patients with UC.
The Harvey-Bradshaw Index calculates single-day scores for
general well-being (previous day; 0 ¼very well to 4 ¼terrible),
abdominal pain (previous day; 0 ¼none to 3 ¼severe), the
number of liquid or soft stools per day (previous day; open
entry with 1–25 possible points), abdominal mass (0 ¼none to
3¼definite and tender), and complications to assess disease
severity (no ¼none, yes ¼all complications with 1 point for
each [1–8]) in patients with CD.
19
The cutoff scores used were
0–4 for remission, 5–7 for mild disease, and 8 for moderate/
severe disease.
19,20
Components of the partial Mayo Score for UC include
measures of rectal bleeding (0 ¼none to 3 ¼passing blood
alone), stool frequency (0 ¼normal to 3 ¼5 or more stools per
day than normal), and the Physician’s Global Assessment of
disease severity (0 ¼normal [for the patient] to 3 ¼severe
disease) that acknowledges the 3 subscores, the daily record of
abdominal discomfort, functional findings, and other observa-
tions such as physical findings and patient performance
928 Cross et al Gastro Hep Advances Vol. 1, No. 6

status.
21,22
The cutoff scores used were 0–1 for remission
(perfect or very good with minimal symptoms), 2–4 for mild
disease, and 5–9 for moderate/severe disease.
21
Patient-Reported Outcomes
Primary outcomes were collected at the enrollment visit
and were compared with disease severity measures. All vari-
ables were provider-reported unless indicated otherwise. All
covariates, including disease severity measures, were also
assessed at the enrollment visit.
PROMIS is a National Institutes of Health–funded instru-
ment that assesses the patient’s self-reported health over the
past 7 days.
23
Patients report different components of phys-
ical, mental, and social health, including anxiety, depression,
fatigue, sleep disturbance, and pain interference, and higher
scores indicate poorer health. A score of 50 represents the
general US population mean, and minimally important differ-
ences of 2–6 points have been reported for other disease
states, including chronic pain, stroke, osteoarthritis, and
cancer.
24,25
Five WPAI domains measure absenteeism (the percentage
of work hours missed due to IBD), presenteeism (the per-
centage of impairment while working due to IBD), work pro-
ductivity loss (the overall percentage of work hours affected by
IBD), and activity impairment (the overall percentage of daily
activities affected by IBD). At enrollment, WPAI scores were
dichotomized to assess the proportion of patients who experi-
enced no (0%) or any (>0%) impairment in the different do-
mains. Absenteeism, presenteeism, and work productivity loss
were measured on the subset of patients currently employed.
Statistical Analysis
Descriptive statistics were used to describe patient enroll-
ment characteristics; categorical variables were summarized
using frequency counts and percentages; continuous variables
were summarized by number of observations, mean, and
standard deviation.
Kruskal-Wallis and chi-square tests were used to investi-
gate associations between disease severity and PROMIS do-
mains. The Cochran-Armitage test for trends was used to
determine associations between disease severity and WPAI
domains. Patients with missing data were not included in the
analyses.
We conducted univariable and multivariable linear or lo-
gistic regression modeling to evaluate the associations between
disease severity groups and (1) the PROMIS domains of anxiety,
depression, fatigue, pain interference, and sleep disturbance, as
well as (2) the following binary WPAI domains: current
employment, absenteeism, presenteeism, work productivity
loss, and activity impairment. Models were adjusted a priori for
potential confounding variables: age, sex, race, duration of
disease, current treatment for IBD (biologics/JAK inhibitors,
immunosuppressants, 5-aminosalicylic acid, corticosteroids,
and antibiotics), and comorbidities using a modified Charlson
Comorbidity Index
26
(see Supplemental Digital Content for the
full regression results).
We calculated adjusted means and 95% confidence in-
tervals of PROMIS scores by disease severity among patients
with CD and UC, evaluating holding covariates in the regression
model at their mean values. Similarly, we calculated adjusted
probabilities and 95% confidence intervals of WPAI scores by
Table 1. Baseline Characteristics Among Patients With
Crohn’s Disease (CD) or Ulcerative Colitis (UC) Enrolled in
the IBD Registry as of September 3, 2019
Variables
Patients
with CD
(n ¼812)
Patients
with UC
(n ¼731)
Age (y), mean (SD) 47.1 (16.8) 47.7 (16.9)
Female, n (%) n ¼809 n ¼728
465 (57.5) 391 (53.7)
White race, n (%) 708 (87.2) 608 (83.2)
Disease duration (y), mean (SD) n ¼807 n ¼726
13.7 (12.3) 10.1 (9.7)
Private health insurance, n (%) 591 (72.8) 543 (74.3)
Work status, n (%) n ¼811 n ¼728
Employed (part time or full time) 527 (65.0) 473 (65.0)
Education, n (%) n ¼810 n ¼727
College educated (some or more) 622 (76.8) 558 (76.8)
Geographic region, n (%) n ¼810 n ¼729
Northeast 116 (14.3) 111 (15.2)
Central 51 (6.3) 49 (6.7)
South 556 (68.6) 482 (66.1)
West 87 (10.7) 87 (11.9)
Site type, n (%) n ¼812 n ¼731
Private 664 (81.8) 667 (91.2)
Academic 148 (18.2) 64 (8.8)
Harvey-Bradshaw index, n (%)
Remission (0–4) 547 (67.4) –
Mild disease (5–7) 156 (19.2) –
Moderate disease (8–16) 103 (12.7) –
Severe disease (>16) 6 (0.7) –
Partial Mayo Score, n (%)
Remission (0–1) –385 (52.7)
Mild disease (2–4) –258 (35.3)
Moderate disease (5–6) –62 (8.5)
Severe disease (7–9) –26 (3.6)
History of extraintestinal manifestations, n
(%)
Arthritis 158 (19.5) 71 (9.7)
Skin manifestations 36 (4.4) 8 (1.1)
Eye involvement 23 (2.8) 2 (0.3)
History of comorbidities, n (%)
Hypertension 158 (19.5) 139 (19.0)
Hyperlipidemia 62 (7.6) 76 (10.4)
Cardiovascular disease 81 (10.0) 73 (10.0)
Diabetes mellitus 44 (5.4) 47 (6.4)
Depression 87 (10.7) 50 (6.8)
Anxiety 104 (12.8) 80 (10.9)
Medication use at enrollment, n (%)
Biologic or JAK inhibitor 492 (60.6) 291 (39.8)
Immunomodulator 138 (17.0) 86 (11.8)
5-Aminosalicylate 157 (19.3) 396 (54.2)
Corticosteroid 111 (13.7) 102 (14.0)
Antibiotic 15 (1.8) 12 (1.6)
IBD-related surgery, n (%) –n¼731
History of proctocolectomy –n¼11
J-pouch creation –10 (90.9)
End ileostomy –1 (9.1)
History of other IBD-related surgery, n (%) n ¼812 n ¼731
Resection 256 (31.5) 8 (1.1)
Ostomy 59 (7.3) 12 (1.6)
Lysis of adhesions 0 (0.0) 0 (0.0)
Other 69 (8.5) 12 (1.6)
IBD, inflammatory bowel disease; JAK, Janus kinase; SD,
standard deviation.
Month 2022 Inflammatory bowel disease remission outcomes 929

disease severity, again evaluating holding covariates at their
mean values.
All authors had access to the study data and reviewed and
approved the final manuscript.
Results
A total of 1660 patients were enrolled in the IBD registry
as of September 3, 2019; of these patients, 1543 were
included in this cross-sectional analysis, and 117 were
excluded due to a diagnosis of indeterminate colitis, a
diagnosis change, or missing disease severity measures.
Crohn’s Disease
Our analysis included a total of 812 patients with CD,
with 67.4% in remission, 19.2% with mild disease, and
13.4% with moderate/severe disease. The mean age at
enrollment was 47.1 years; 57.5% were female and 87.2%
were White. The mean disease duration at enrollment was
13.7 years. These and other baseline characteristics are
presented in Table 1.
Overall unadjusted PROMIS and WPAI scores indi-
cate a high burden of psychosocial and work impair-
ment in the CD cohort (Figures 1 and 2). Although
patients with mild and moderate/severe disease re-
ported more impairment than patients in remission,
impaired PROs were commonly reported even among
patients with CD in remission. For the patients with CD
in remission, the unadjusted percentage of patients with
PROMIS scores outside of normal limits ranged from
18.9% (depression) to 34.9% (fatigue). In addition,
54.3% of patients with CD in remission reported work
19.3%
19.2%
23.1%
10.8%
19.2%
26.9%
6.4% 12.0%
67.5%
55.1%
38.0%
14.9%
21.6%
15.9%
12.3%
14.1%
33.0%
4.3% 6.8%
71.5%
60.0%
44.3%
11.7%
15.4%
18.5%
6.4%
13.5%
19.4%
5.6%
81.1%
69.2%
56.5%
11.2%
11.7%
21.6%
4.2% 9.7%
20.5%
84.3% 78.2%
56.8%
15.9%
18.7%
18.7%
16.4%
36.8%
43.0%
3.9%
18.7%
65.1%
40.6%
19.6%
14.5%
14.0%
16.1%
12.4%
19.6%
42.5%
4.0% 9.2%
71.2%
62.4%
32.2%
14.7%
26.9%
14.7%
13.8%
31.4%
45.9%
3.8%
11.0%
69.5%
37.8%
28.4%
14.1%
19.1%
25.0%
12.0%
21.9%
28.4%
5.7%
72.9%
57.4%
40.9%
13.8%
16.1%
27.1%
9.2%
15.5%
21.5%
5.6%
76.4%
66.5%
45.8%
10.4%
16.4%
13.6%
6.5% 10.5%
26.1%
82.0%
71.1%
59.1%
Anxiety Depression Fatigue Pain interference Sleep disturbance
CD
UC
Remission Mild Moderate/
Severe
Remission Mild Moderate/
Severe
Remission Mild Moderate/
Severe
Remission Mild Moderate/
Severe
Remission Mild Moderate/
Severe
0
20
40
60
80
100
0
20
40
60
80
100
Disease Severity
Percent
PROMIS Score Within normal limits Mild Moderate Severe
Figure 1. Stacked bar plots of unadjusted percentage reporting impairment in each PROMIS score domain. Kruskal-Wallis and
chi-square tests were used to investigate associations between disease severity and PROMIS domains for continuous and
categorical variables, respectively. Unadjusted analyses indicate that they were not controlled for age, sex, race (White vs non-
White), duration of disease, current treatment, and comorbidities. Patients with missing data were not included in the analysis.
“Severe”scores not reported in the figure owing to space (were below 3.5%). All Pvalues <.001 for CD and UC. CD, Crohn’s
disease; PROMIS, Patient-Reported Outcomes Measurement Information System; UC, ulcerative colitis.
930 Cross et al Gastro Hep Advances Vol. 1, No. 6

productivity loss, and 57.1% reported activity
impairment.
Adjusted estimated means for the PROMIS scores
27,28
for patients with CD exceeded the threshold for
“normal”among the general population (ie, estimated
mean 55) for patients with mild disease in the domains
of fatigue (55.4) and pain interference (57.4), and for
patients with moderate/severe disease in the domains of
anxiety (56.6), fatigue (59.9), pain interference (61.3), and
sleep disturbance (57.0; Table 2). Adjusted estimated
probabilities for the WPAI scores exceeded 50% for pa-
tients with CD in remission for any presenteeism, any
work productivity loss, and any activity impairment.
Higher probabilities were observed in mild and moderate/
severe CD as well (Table 3). In addition, greater disease
severity for patients with CD was associated with worse
outcomes on both the PROMIS and WPAI measures (see
Tables A1
15,24,28
and A2).
Ulcerative Colitis
Our analysis included a total of 731 patients with UC,
with 52.7% in remission, 35.3% with mild disease, and
12.0% with moderate/severe disease. The mean age at
enrollment was 47.7 years; 53.7% were female and 83.2%
were White. The mean disease duration was 10.1 years.
These and other demographic details are presented in
Table 1.
As seen in the CD cohort, overall unadjusted PROMIS and
WPAI scores indicate a high burden of mental and physical
distress and work impairment in patients with UC as well
(Figures 1 and 2). Impaired PROs were commonly reported
in all patients with UC, including those in remission. The
unadjusted percentage of patients with UC in remission with
scores outside of normal limits ranged from 15.7%
(depression) to 28.7% (fatigue) for PROMIS domains and
10.5% (absenteeism) to 43.5% (activity impairment) for
WPAI domains.
68.1%
62.8%
56.0%
66.4% 65.4%
69.3%
14.1%
26.8%
48.3%
10.5%
16.4%
49.1%
52.2%
82.7%
90.0%
38.2%
71.9%
91.4%
54.3%
85.6%
89.7%
39.2%
76.3%
90.9%
57.1%
87.2%
93.5%
43.5%
71.5%
93.1%
Currently employed Any absenteeism Any presenteeism Any work productivity loss Any activity impairment
CD
UC
Remission Mild Moderate/
Severe
Remission Mild Moderate/
Severe
Remission Mild Moderate/
Severe
Remission Mild Moderate/
Severe
Remission Mild Moderate/
Severe
0
20
40
60
80
100
0
20
40
60
80
100
Disease Severity
Percent
Figure 2. Bar plots of unadjusted percentage reporting impairment in each WPAI domain. The Cochran-Armitage test for
trends was used to determine associations between disease severity and WPAI domains. Unadjusted analyses indicate that
they were not controlled for age, sex, race (White vs non-White), duration of disease, current treatment, and comorbidities.
All Pvalues <.001 for CD and UC except for “Currently employed”in CD (P¼.011) and “Currently employed”in UC
(P¼.776).CD, Crohn’s disease; UC, ulcerative colitis; WPAI, Work Productivity and Activity Impairment.
Month 2022 Inflammatory bowel disease remission outcomes 931

Adjusted estimated means for the PROMIS scores
27,28
for
patients with UC exceeded normal limits among patients
with moderate/severe disease in the domains of anxiety
(57.9), fatigue (58.7), and pain interference (58.1; Table 2).
The adjusted estimated probabilities for the WPAI scores
exceeded 50% for patients with UC in remission for any
presenteeism. Higher probabilities were observed in mild
and moderate/severe UC as well (Table 3). Finally, as seen
in the CD cohort, greater disease severity for patients with
UC was associated with worse outcomes on both the
PROMIS and WPAI measures (see Tables A3
15,24,28
and A4).
In an exploratory regression analysis, disease activity
coefficients were only mildly attenuated after adjusting for
college education and history of surgery, and no meaningful
changes were observed.
Discussion
In our study, patients with IBD, including those in
remission, experienced impaired PROMIS outcomes and
work productivity. Although patients with greater disease
severity reported poorer QOL and work-related outcomes,
our observation of significant impairment in psychosocial
function and activity for CD and UC patients in remission,
which represented about 50%–70% of IBD patients in our
study, highlights a critical unmet need in this population.
Our study results are consistent with previous research.
A large study using data from the Crohn’s and Colitis
Foundation Partners internet cohort reported that disease
activity was associated with higher PROMIS scores both
cross-sectionally and longitudinally.
13
In addition, a sub-
stantial proportion of patients with IBD have impaired
presenteeism as shown by the percentage of work hours
impacted by IBD in a recent study.
29
A previous study of
patients with IBD reported significant economic burden
associated with work productivity loss and activity impair-
ment.
30
Although studies have shown there is an incre-
mental increase in WPAI scores as CD and UC worsen from
remission to severe disease,
18,31
no study to our knowledge
has examined PRO impairment in patients in remission.
PRO instruments such as PROMIS and the WPAI ques-
tionnaire provide important information about the patient
experience that may be underrepresented by physician-
reported disease activity indices. As in many other chronic
illnesses, individuals with IBD may suffer from psychosocial
and physical stress (eg, depression, anxiety, fatigue, pain
interference, sleep disturbance), which can worsen QOL
and/or exacerbate symptoms of disease. Depression and
anxiety have been shown to predict clinical reoccurrence,
regardless of remission status.
2,11,32
The high burden of
psychological distress within our cohorts emphasizes the
importance of mental health screening and treatment, irre-
spective of disease activity.
13
One symptom of interest was fatigue, which has been
associated with poor general and disease-specific health-
related QOL, disability, and depression in patients with
IBD.
10
Pain, fatigue, and other disease-related symptoms are
frequently cited reasons for missed work among patients
with IBD.
3
Fatigue has been reported in IBD by up to 48% of
patients in remission and 86% of patients with active dis-
ease.
33
We also noted persistent fatigue symptoms outside
of normal limits in both patients with UC and CD in remis-
sion within our study. Fatigue in IBD can be exacerbated by
sleep disturbance and associated with physical and mental
symptoms that limit the patients’social, physical, and work
activities.
34,35
A study of 220 newly diagnosed patients with
IBD
10
demonstrated that fatigued patients had more work
impairment (difference: CD, 29.5%; UC, 23.8%) and activity
impairment (difference: CD, 32.3%; UC, 25.7%) than those
without fatigue. After controlling for disease activity, a
Table 2. Adjusted Estimated Means of PROMIS Scores
27,28
by Disease Severity Among Patients With Crohn’s Disease
(N ¼812)
a
and Ulcerative Colitis (N ¼731)
PROMIS domains
b
Adjusted means for Crohn’s disease
b
Adjusted means for ulcerative colitis
b
Remission Mild Moderate/severe Remission Mild Moderate/severe
Mean (95% CI) Mean (95% CI) Mean (95% CI) Mean (95% CI) Mean (95% CI) Mean (95% CI)
Anxiety 50.0 (47.1, 52.9) 53.2 (50.1, 56.3) 56.6 (53.3, 59.8) 51.4 (48.3, 54.5) 53.8 (50.7, 56.9) 57.9 (54.7, 61.2)
Depression 46.6 (44.0, 49.3) 49.8 (47.0, 52.6) 52.2 (49.3, 55.1) 49.0 (46.4, 51.5) 50.4 (47.8, 53.0) 54.6 (51.8, 57.3)
Fatigue 49.6 (46.4, 52.7) 55.4 (52.1, 58.7) 59.9 (56.5, 63.3) 49.1 (45.6, 52.7) 52.3 (48.7, 55.8) 58.7 (55.0, 62.4)
Pain interference 51.5 (48.6, 54.3) 57.4 (54.4, 60.5) 61.3 (58.2, 64.5) 51.1 (48.1, 54.1) 54.3 (51.3, 57.4) 58.1 (54.9, 61.3)
Sleep disturbance 50.7 (48.1, 53.2) 54.2 (51.5, 57.0) 57.0 (54.2, 59.8) 48.5 (45.7, 51.3) 51.0 (48.1, 53.8) 54.6 (51.7, 57.6)
A higher score denotes more symptoms on that scale and a minimally important difference for the psychosocial PROMIS
domain scales ranges from 2 to 6.
15,24,28
PROMIS, Patient-Reported Outcomes Measurement Information System.
a
General population thresholds are the following: within normal limits (<55), mild (55, <60), moderate (60, 65), severe (>65)
with an overall average of 50.
27
b
Adjusted estimated means from corresponding multivariable regression model adjusted a priori for age, sex, race (White vs
non-White), duration of disease, current treatment, and comorbidities; evaluated holding covariates at their mean values.
932 Cross et al Gastro Hep Advances Vol. 1, No. 6

significant association was found between fatigue and
impairment scores.
10
Our study demonstrates that patients with moderate to
severe CD/UC have physical and psychosocial symptoms
that further impact work productivity. We observed that a
substantial proportion of patients with IBD in remission
experienced productivity loss at work (CD, 54%; UC, 39%;
Figure 2). It is possible that the symptoms are interrelated,
making it difficult to determine what symptom is primarily
impacting work productivity impairment. A potential
explanation for the impaired PROs in patients in symp-
tomatic remission includes the presence of subclinical
inflammation. It is well known that there can be a discon-
nect between symptoms and inflammation; in a study of 121
patients with CD, only weak correlations were found be-
tween the severity of symptoms and the level of inflam-
mation.
36,37
Therefore, patients in remission or with mild
symptoms may still have significant inflammation resulting
in impaired PROs. This emphasizes the need for gastroen-
terologists to adopt a treat-to-target approach to verify
control of inflammatory activity regardless of symptoms.
38
Our findings provide additional motivation for exam-
ining the relationship between psychosocial factors, such as
depression and anxiety, and poor clinical outcomes in pa-
tients with IBD. There have been limited studies sur-
rounding QOL and PROs in IBD patients in remission, and
our findings help to address this important gap within the
literature. The results of our study contrast with one pre-
vious study that found the psychological well-being of IBD
patients in long-standing remission was similar to that of
the general public.
39
Future research should include addi-
tional comparisons to the general public to further under-
stand the symptomatic burden that patients with IBD in
remission still experience.
The strengths of this study include the sample size, use
of validated indices, and geographic distribution of the
cohort. Our findings contribute to the currently limited body
of knowledge on the relationship between disease activity
measures and PROs in patients with IBD.
This study is subject to the limitations of real-world
observational studies. It includes health care providers
with high proportions of patients with IBD, which may
bias the results to a more refractory population not
representative of the general US IBD population. In
addition, the patient population was predominantly
White, privately insured, employed, and highly educated
(some college and beyond). This limits the ability to
generalize these data across diverse patient populations,
including those from lower socioeconomic groups. Recent
literature suggests that social determinants (markers of
lower socioeconomic status) impact IBD outcomes,
thereby warranting further research in a more diverse
patient population.
40,41
As this was a cross-sectional analysis, causal inferences
cannot be made regarding disease severity and PROs, and
changes in disease severity and PROs over time were not
measured. In addition, there is a lack of objective markers of
disease activity such as endoscopy or disease markers using
labs/fecal laboratory values.
In this study, patients in remission showed impairment
in PROs, highlighting how those in remission may still need
active management. Further investigation into the factors
that impact persistent PRO impairment is warranted. Even
in remission, the prevalence of fatigue, pain, and anxiety/
depression is high, which affects QOL and work
productivity.
Conclusions
In our study of patients with IBD, psychosocial impair-
ment and decreased work productivity were seen even in
patients in remission, who made up approximately 67% and
53% of patients in the CD and UC cohorts, respectively. The
prevalence of self-reported fatigue, pain, and anxiety and
depression remains high among patients with IBD in
remission and indicates that there may be important aspects
of disease impacting patients’lives that have not been
captured in standard disease activity assessments.
Table 3. Adjusted Estimated Probabilities of WPAI Scores by Disease Severity Among Patients With Crohn’s Disease (N ¼
812)
a
and Ulcerative Colitis (N ¼731)
WPAI domains
b
Adjusted probabilities
b
for Crohn’s disease Adjusted probabilities
b
for ulcerative colitis
Remission Mild Moderate/severe Remission Mild Moderate/severe
% (95% CI) % (95% CI) % (95% CI) % (95% CI) % (95% CI) % (95% CI)
Currently employed 69.9 (53.6, 82.4) 65.0 (46.9, 79.6) 57.8 (39.1, 74.6) 81.7 (64.1, 91.7) 79.5 (60.6, 90.7) 78.8 (59.0, 90.6)
Any absenteeism 26.0 (13.0, 45.2) 42.2 (23.0, 64.1) 67.6 (44.5, 84.5) 18.3 (7.7, 37.5) 26.0 (11.6, 48.4) 60.7 (36.8, 80.4)
Any presenteeism 63.1 (35.0, 84.5) 89.0 (70.2, 96.5) 92.6 (75.5, 98.1) 51.1 (27.9, 73.9) 80.6 (59.9, 92.0) 93.8 (80.9, 98.2)
Any work productivity loss 64.1 (35.8, 85.2) 90.8 (73.7, 97.2) 92.1 (74.2, 97.9) 46.9 (24.2, 71.0) 80.8 (59.7, 92.3) 92.3 (76.8, 97.8)
Any activity impairment 62.6 (41.2, 80.0) 89.5 (76.5, 95.7) 94.5 (84.7, 98.1) 46.3 (26.7, 67.1) 72.7 (52.7, 86.4) 92.9 (81.0, 97.5)
WPAI, Work Productivity and Activity Impairment.
a
All domain scores are expressed as percentages, with lower values indicating less impairment.
b
Adjusted probabilities from corresponding multivariable logistic regression model; evaluated holding covariates at their
mean values.
Month 2022 Inflammatory bowel disease remission outcomes 933

Supplementary Materials
Material associated with this article can be found in the
online version at https://doi.org/10.1016/j.gastha.2022.07.
003.
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Received November 18, 2021. Accepted July 6, 2022.
Correspondence:
Address correspondence to: Raymond K. Cross, MD, MS, Professor of Med-
icine, University of Maryland School of Medicine, 685 W. Baltimore Street,
Suite 8-00, Baltimore, Maryland 21201. e-mail: rcross@som.umaryland.edu.
Acknowledgments:
The authors would like to thank Rachel H. Mackey, PhD, for her contributions to
the research.
Authors’Contributions:
Raymond K. Cross, Jenny S. Sauk, Joe Zhuo, Harris A. Ahmad, Antoine G.
Sreih, Joehl Nguyen, Sara N. Horst, and David Hudesman designed the study.
Joe Zhuo, Ryan W. Harrison, Samantha J. Kerti, Kelechi Emeanuru, and Jac-
queline O’Brien contributed to collection and assembly of data. Ryan W.
Harrison and Samantha J. Kerti contributed to data analysis. All authors
contributed to data interpretation, article review and revisions, and final
approval of the article.
Conflicts of Interest:
These authors disclose the following: R.K.C. is a member of advisory boards at
AbbVie, Bristol Myers Squibb, Janssen, Samsung Bioepis, and Takeda;
consultant at AbbVie and Eli Lilly and Company. J.S.S. is a consultant for
CorEvitas; is a member of speakers’bureau of Pfizer Inc and AbbVie; is a
member of advisory board at Prometheus. S.N.H. is a consultant at Janssen,
Boehringer Ingelheim, and Gilead. D.H. is a consultant at Bristol Myers Squibb,
AbbVie, Janssen, Pfizer Inc, and Takeda; and received research support from
Takeda. J.N. was a consultant at Bristol Myers Squibb at the time of the study
and is currently employee of GlaxoSmithKline. J.Z., H.A., and A.G.S. are em-
ployees and may be shareholders of Bristol Myers Squibb. R.W.H., S.J. K., K.E.,
and J.O. are employees of CorEvitas LLC.
Funding:
This study was sponsored by CorEvitas, LLC, and the analysis was funded by
Bristol Myers Squibb. Access to study data was limited to CorEvitas, and
CorEvitas statisticians completed all analyses; all authors contributed to the
interpretation of the results. CorEvitas has been supported through contracted
subscriptions in the last 2 years by AbbVie, Amgen, Arena , Boehringer Ingel-
heim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly and Company, Gen-
entech, Gilead, GSK, Janssen, LEO, Novartis, Ortho Dermatologics, Pfizer Inc,
Regeneron, Sanofi, Sun, and UCB. Professional medical writing from LeeAnn
Braun, MPH, MEd, and editorial assistance were provided by Peloton Advan-
tage, LLC, an OPEN Health company, and were funded by Bristol Myers
Squibb. This article was a collaborative effort between CorEvitas and Bristol
Myers Squibb, with financial support provided by Bristol Myers Squibb.
Ethical Statement:
The corresponding author, on behalf of all authors, jointly and severally, cer-
tifies that their institution has approved the protocol for any investigation
involving humans or animals and that all experimentation was conducted in
conformity with ethical and humane principles of research.
Data Transparency Statement:
Bristol Myers Squibb shares data from BMS studies that meet our data sharing
criteria with qualified researchers who submit a data sharing proposal at:
https://www.bms.com/researchers-and-pa rtners/independent-research/data-
sharing-request-process.html. The website provides additional information on
(1) submitting a sharing request for BMS data, (2) criteria for studies “in scope”
for data sharing, (3) process for submitting data sharing requests, including
review of in-scope proposals by the Independent Review Committee (IRC), and
(4) Bristol Myers Squibb’s disclosure commitment.
Month 2022 Inflammatory bowel disease remission outcomes 935