Rectal Urgency Among Patients With Ulcerative Colitis or Crohn’s Disease: Analyses from a Global Survey

Abstract Background Rectal urgency is a common but under-reported inflammatory bowel disease (IBD) symptom. The present study assessed the prevalence of rectal urgency and its association with disease activity and patient-reported outcomes (PROs) among patients with ulcerative colitis (UC) or Crohn’s disease (CD) in a real-world setting. Methods Data were drawn from the 2017–2018 Adelphi IBD Disease Specific Programme™, a multi-center, point-in-time survey of gastroenterologists and consulting adult patients with UC or CD in France, Germany, Italy, Spain, the United Kingdom, and the United States. Gastroenterologists completed patient record forms and patients completed self-reported forms. Analyses were conducted separately for patients with UC or CD. Patient demographics, clinical characteristics, disease activity, symptoms, and PROs were compared between patients with and without rectal urgency. Results In total, 1057 patients with UC and 1228 patients with CD were included. Rectal urgency was reported in 20.2% of patients with UC and 16.4% with CD. Patients with rectal urgency were more likely to have moderate or severe disease (UC or CD: P < .0001), higher mean Mayo score (UC: P < .0001), higher mean Crohn’s Disease Activity Index score (CD: P < .0001), lower Short IBD Questionnaire scores (UC or CD: P < .0001), and higher work impairment (UC: P < .0001; CD: P = .0001) than patients without rectal urgency. Conclusions Rectal urgency is a common symptom associated with high disease activity, decreased work productivity, and worse quality of life. Further studies are needed to include rectal urgency assessment in routine clinical practice to better gauge disease activity in patients with UC or CD.


Introduction
Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases that cause chronic inflammation of the gastrointestinal tract. 1,2][7][8][9][10] Rectal urgency is considered an important clinical manifestation and a strong predictor for clinical disease activity in UC or CD. 11,12Patients consider rectal urgency to be a more relevant and important symptom than abdominal pain, blood in stools, or stool frequency. 12,139][20][21][22] Limited global data are available on the prevalence of rectal urgency and its association with disease activity and patient-reported outcomes (PROs), such as EQ-5D-5L, Short IBD Questionnaire (SIBDQ), and Work Productivity and Activity Impairment (WPAI) among patients with UC or CD.The present study aimed to investigate the prevalence of rectal urgency in patients with UC or CD in a global cross-sectional survey.We also evaluated the association of rectal urgency with disease activity and PROs.

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Rectal Urgency Among Patients with Ulcerative Colitis or Crohn's Disease

Data Source and Collection
Data were drawn from the Adelphi IBD Disease Specific Programme (DSP), a point-in-time survey. 234][25] Gastroenterologists and their consulting adult patients with UC or CD from France, Germany, Italy, Spain, the United Kingdom, and the United States were surveyed.Data were collected via gastroenterologist-completed patient record forms (PRF) and patient-self-completed (PSC) forms.][7][8][9][10] Here, we used "rectal urgency" throughout the study as it was the term used in the survey conducted as a part of Adelphi DSP.
Gastroenterologists were identified from publicly available lists of healthcare professionals (HCPs) and invited to participate in the survey.The gastroenterologists had to have treated at least seven patients with UC and at least eight patients with CD on average in a month.Patients aged > 18 years with a diagnosis of UC or CD, as recorded on the PRF, were included.Patients were required to have a gastroenterology clinic visit during the study period.Gastroenterologists were requested to complete a PRF for the next seven to eight consecutive patients who visited them for consultation.The PRF contained detailed questions on patient demographics, clinical characteristics (disease severity and symptoms), disease activity, and medication use.Categories related to remission status (not in remission or in remission) were included and reported by the gastroenterologist.Following physician consultation, patients were invited to voluntarily complete a paper survey using PSC forms.All participating gastroenterologists and patients were assigned a study number to aid anonymous data collection and to allow linkage of data during data collection and analysis.
The PSC form contained questions on general symptoms including the following: (1) Which of the following symptoms they are currently experiencing: rectal urgency, fatigue, abdominal pain, sleep disturbance, etc.? (2) What is the current level of severity for each symptom?, and (3) Which are the top three symptoms most difficult to resolve?Levels of overall pain and sleep disturbance were measured on a scale of 0-10 (0 = no pain or no sleep disturbance to 10 = severe pain or sleep disturbance).The PSC form also contained PROs such as the WPAI, SIBDQ, and EQ-5D-5L.The WPAI: General Health V2.0 measures work productivity-related domains (absenteeism, presenteeism, work productivity loss, and activity impairment).Higher impairment percentages indicate greater work impairment and less productivity. 26he SIBDQ instrument measures various aspects of HRQoL (bowel, systemic, social, and emotional domains), with scores ranging from 10 to 70.Lower SIBDQ scores indicate poor HRQoL. 27,28The EQ-5D-5L, which is based on EQ-5D, 29,30 measures health in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) using five levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). 31

Outcome Measures
Patient demographics included age, sex, ethnic origin, smoking status, employment status, current (at point of consultation and data collection) level of disease severity (UC or CD), and current type of CD.Disease activity was measured by Mayo score (UC) and Crohn's Disease Activity Index (CDAI) score (CD).Mayo score was calculated based on stool frequency, rectal bleeding, endoscopic findings, and Physician's Global Assessment (PGA).Symptoms captured included level of abdominal pain and fatigue/tiredness.For CDAI, general well-being, extra-intestinal conditions, and presence of an abdominal mass were recorded.Severity of abdominal pain and current IBD medication regimen (biologics/non-biologics) were recorded for patients with UC or CD.Quality of life measures included EQ-5D-5L, SIBDQ, and WPAI.The results present in the study included combined survey results of both gastroenterologists and patients.

Statistical Methods
Demographics, clinical characteristics, disease activity, symptoms, and PROs were compared between patients with and without rectal urgency using parametric and nonparametric tests, where appropriate.T-tests were performed to determine statistical differences between the means of the groups for numerical outcomes.Fisher's exact test was used for dichotomous variables, and Chi-squared test was used for categorical variables.All analyses were conducted for UC or CD groups separately.Missing data were not imputed; therefore, the number of patients included for analysis may vary for each variable and is reported separately for each analysis.
Data were presented as mean and standard deviation (SD) for continuous variables.Frequencies and percentages were reported for categorical variables.Logistic regressions were used to identify risk factors associated with rectal urgency.In the regression models, rectal urgency was considered as the dependent variable.Independent variables included disease activity (Mayo for UC; CDAI for CD), fatigue, abdominal pain, overall pain, sleep disturbance, stool frequency (UC only), rectal bleeding (UC only), severity of abdominal pain (CD only), general well-being (CD only), PRO scales (EQ-5D-5L, SIBDQ, and WPAI), and medication use.Regressions were adjusted for confounders: age, sex, body mass index, and the Charlson Comorbidity Index.Standard errors from the regressions were adjusted to allow for intra-group correlation within reporting physician, relaxing the assumption that all observations are independent.
Odds ratios (ORs) with 95% confidence interval (CI) were reported for each of the covariates used in the regression model.Two-sided P-values were considered for all the statistical tests, and a significance level of α < .05 was considered to be statistically significant.All statistical tests were performed using Stata software (Version 16) (Stata Corp. 2019).

Ethical Considerations
All the survey responses captured on the data collection forms were anonymized to preserve respondent (physician and patient) confidentiality.All materials were reviewed and approved by the Western Institutional Review Board.Patients provided their consent to complete the PSC form in accordance with the Health Insurance Portability and Accountability Act, 32 Health Information Technology for Economic and Clinical Health Act (HITECH Act), and the

Prevalence of Rectal Urgency and Patient Characteristics in the UC Cohort
A total of 20.2% (n = 213) of patients with UC reported rectal urgency (Table 1).Overall, 47% and 49% of patients were female in the rectal urgency and without rectal urgency groups, respectively.Mean age (SD) of patients with and without rectal urgency was 38.6 (14.8) years and 40.5 (14.9) years, respectively.A majority of the patients were White/ Caucasian in both with and without rectal urgency groups (Table 1).Patients with rectal urgency presented a higher disease burden than those without in both moderate (54.5% vs. 38.5%)and severe categories of disease severity (8% vs. 4.5%), as assessed by the PGA.Demographic variables were not significantly different between patients with and without rectal urgency (Table 1).

Prevalence of Rectal Urgency and Patient Characteristics in the CD Cohort
A total of 16.4% (n = 202) of patients with CD reported rectal urgency ( Patients with rectal urgency were overrepresented in the moderate disease category compared to those without (59.4% vs. 35.0%),whereas they were slightly underrepresented in the severe disease category (4.5% vs. 5.5%).Demographic variables were not significantly different between patients with and without rectal urgency (Table 2).

Association of Disease Activity and PROs With Rectal Urgency in the UC Cohort
Patients reporting rectal urgency were more likely to have moderate or severe disease (P < .0001)and a higher mean Mayo score (P < .0001)compared to those without rectal urgency (Table 1).Similarly, patients with rectal urgency were less likely to be in remission and have a disease activity index score of 0 compared to patients without rectal urgency (P < .0001).Patients with rectal urgency were more likely to have active disease, particularly moderate or severe disease, compared to patients without rectal urgency (P < .0001;Table 1).Patients with rectal urgency reported a greater degree of stool frequency and rectal bleeding than patients without rectal urgency (P < .0001;Table 1).Patients with rectal urgency were more likely to have fatigue (P < .0001),abdominal pain (P < .0001),higher levels of overall pain (P < .0001),and higher levels of sleep disturbance than patients without rectal urgency (P < .0001;Table 1).The mean SIBDQ and EQ-5D-5L scores were lower and the mean WPAI scores were higher in patients with rectal urgency compared to those without rectal urgency, indicating a lower HRQoL in patients with rectal urgency (SIBDQ mean [SD]: 4.6 [1.0] vs. 5.3 [1.1], P < .0001;EQ-5D-5L: 0.8 [0.2] vs. 0.8 [0.2], P < .0001;WPAI: 41.8 [30.1] vs. 25.0 [26.9],P < .0001;Table 1).Medication use was not significantly different in patients with and without rectal urgency (Table 1).Logistic regression analysis observed that the odds of having rectal urgency in patients with UC were lower with higher SIBDQ scores (OR: 0.62; 95% CI: [0.48 − 0.80]; P < .0001);5-aminosalicylic acid (ASA) use (OR: 0.54; 95% CI: [0.34 − 0.85]; P = .008),and with the use of biologics/biosimilars (OR: 0.61; 95% CI: [0.41 − 0.91]; P = .015;Figure 1).Among patients with rectal urgency, stool frequency, and rectal bleeding were not significantly different when compared to patients without rectal urgency (Figure 1).

Association of Disease Activity and PROs With Rectal Urgency in the CD Cohort
The current remission status was significantly different among CD patients with and without rectal urgency (P < .0001;Table 2).Patients with rectal urgency were more likely to have active disease (P < .0001),particularly moderate or severe disease, as well as higher mean CDAI scores (P < .0001)compared to patients without rectal urgency (Table 2).A higher percentage of patients with rectal urgency were prescribed 5-ASAs (72.8% vs. 64.7%;P = .0282),while biologics use was most prevalent amongst patients without rectal urgency (38.1% vs. 48.1%;P = .0108;Table 2).

Discussion
Rectal urgency an important symptom experienced by patients with IBD. 10 It contributes to reduced quality of life; however, it remains under-investigated to date.The present study was conducted based on data drawn from a multinational point-in-time survey of gastroenterologists and their consulting patients with UC or CD to assess the burden of rectal urgency in a real-world clinical practice setting.In general, the terms "bowel urgency" and "rectal urgency" are used interchangeably in IBD studies. 5-10However, we used "rectal urgency" throughout the current study as it was the term used in the survey conducted as a part of Adelphi DSP.In this study, the prevalence of rectal urgency was 20% among patients with UC and 16% among patients with CD.Our findings suggest that patients with UC or CD having rectal urgency were more likely to have moderate or severe disease compared to those without rectal urgency, while patients without rectal urgency were more likely to be in remission.Our findings also suggest that rectal urgency was significantly associated with higher disease activity (Mayo score in patients with UC; CDAI score in patients with CD) and lower SIBDQ (poorer HRQoL).However, the use of agents with known mucosal healing outcomes, 37 such as biologics and 5-ASAs, was associated with decreased likelihood of rectal urgency.Similarly, increased overall pain scores and reduced SIBDQ scores were significantly associated with rectal urgency in patients with CD.These findings indicate reduced well-being among IBD patients with rectal urgency.
To date, only a few global studies have estimated rectal urgency in patients with UC or CD.Previous clinical studies reported the presence of rectal urgency in 31.4%-91.7% of patients with UC and 33.8%-86.7% of patients with CD. 4,7,9,10,15,18,38,39 The difference in prevalence of rectal urgency between current and previous studies could be attributed to the differences in disease severity/remission status and lack of inclusion of definition of rectal urgency in the survey questions.In another real-world study, greater disease activity at enrollment in the cohort was associated with deteriorating fecal urgency symptoms over 6 months in patients with UC or CD. 40ven though our data show the meaningful impact of rectal urgency on IBD patients' clinical activity and quality of life, rectal urgency is often not discussed in clinical practice due to patient hesitation or embarrassment. 15,192][43] Validated PROs developed per FDA guidance (FDA 2009) to assess bowel urgency, 44 such as the Urgency Numeric Rating Scale (Urgency NRS), 41 have only recently become available.Rectal urgency is not only an important marker of disease activity, but also a key factor that should be considered when assessing response to therapy and remission.Future research should include rectal urgency assessments when developing robust and reliable clinical indices for clinical practice and clinical trials.HCPs should include rectal urgency in their routine assessments when evaluating patients IBD and factor the presence of urgency into shared decision-making and treat to target discussions.

Limitations
Given the nature of the point-in-time study design, there may be recall bias as patients had to fill in PSC forms.However, the data for these analyses were collected at the time of each patient's appointment, and this is expected to reduce the likelihood of recall bias.As the recruitment strategy focused only on gastroenterologist consulting patients, the results cannot be generalized.

Conclusions
In the current study, rectal urgency was identified as a common symptom among patients with UC or CD and was associated with higher levels of disease activity, decreased work productivity, and worse HRQoL.Rectal urgency is an important PRO to consider when monitoring response to treatment in addition to stool frequency or rectal bleeding for patients with UC and stool frequency or abdominal pain for patients with CD.Therefore, a better understanding of the PROs and clinical manifestations associated with rectal urgency in patients with UC or CD may help improve disease control.Further investigation may be required to standardize rectal urgency assessment as a metric of disease activity in clinical practice.

Figure 1 .
Figure 1.Logistic regression analyses for rectal urgency in patients with ulcerative colitis.ASA = aminosalicylic acid; BMI = body mass index; CI = confidence interval; SIBDQ = Short Inflammatory Bowel Disease Questionnaire; UC = ulcerative colitis; OR = odds ratio; Odds ratios were computed in the regressions and, for categorical outcomes, are in comparison to the baseline reference categories: No fatigue, no abdominal pain, stool frequency (normal number of stools), no blood seen, medication use (not 5-ASA, not corticosteroid, not immunomodulators, not biologics/ biosimilars).

Table 1 .
Comparison of demographics and clinical characteristics among patients with ulcerative colitis, with and without rectal urgency patients with UC and 1228 patients with CD completed the PSC form and were included in the analysis.The patients included in the analysis were from France (UC: 208, CD: 255), Germany (UC: 303, CD: 350), Italy (UC: 76, CD: 101), Spain (UC: 160, CD: 150), United Kingdom (UC: 40, CD: 44), and the United States (UC: 270, CD: 328).The results pertain to global analyses and are not presented as region-specific data.

Table 2
).Overall, 46.5% and 51.0% of patients were female in the rectal urgency and without rectal urgency groups, respectively.The mean (SD) age of patients with and without rectal urgency was 38.7 (13.1) and 38.5(13.6)years,respectively.A majority of the patients were White/Caucasian in both with and without rectal urgency groups (Table2).n = number of patients; ASA = aminosalicylic acid; UC = ulcerative colitis; SD = standard deviation; SIBDQ = Short Inflammatory Bowel Disease Questionnaire; WPAI = Work Productivity and Activity Impairment; PGA = Physician's Global Assessment; a Level of pain was measured on a scale from 0 = no pain to 10 = severe pain; b Level of sleep disturbance was measured on a scale from 0 = no sleep disturbance to 10 = severe sleep disturbance; c Data are rounded off to single decimal points (Mean EQ-5D-5L scores: rectal urgency = .800and no rectal urgency = .848);*Statistical significance of α < .05.T-test was conducted for numerical data; Fisher exact test for dichotomous outcomes; Chi-square test for categorical variables.

Table 2 .
Comparison of demographics and clinical characteristics among patients with Crohn's disease, with and without rectal urgency

Table 2 .
Level of sleep disturbance was measured on a scale from 0 = no sleep disturbance to 10 = severe sleep disturbance; *statistical significance of α < .05.Continued b