Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory bowel disease (IBD) with variable and heterogeneous courses.¹ The clinical courses of UC and CD and the effects of treatment are assessed using patient-reported signs and symptoms and endoscopic evidence of inflammation.^2,3 The characteristic signs and symptoms of UC and CD encompass abdominal pain, recurrent diarrhea, urgency in bowel movements, and rectal bleeding. These manifestations not only cause distress to patients but also have a detrimental impact on their quality of life (QoL).⁴ IBD not only has a physical impact on patients, but also impairs their social and occupational well-being due to factors such as chronicity, early age of onset, hospitalization, and the need for medical and surgical treatment.^5,6 Based on this background, the recent STRIDE-II consensus set normalized QoL as a long-term target for the treatment of IBD.⁷ Therefore, we need to pay more attention to QoL in patients with IBD.

Several factors significantly affecting the health-related QoL (HRQoL) of individuals with IBD have been identified.^8,9 These factors include, but are not limited to, corticosteroid treatment, episodes of hospitalization, symptoms resembling irritable bowel syndrome, mood disorders, and the frequency of disease relapses. Additionally, sociodemographic variables such as sex, smoking habits, work disability, and unemployment significantly influence the HRQoL of individuals with IBD.^10,11

Typically, objective indicators provide insights into the effectiveness of IBD treatments; however, this study not only focused on this but also analyzed the subjective aspects of QoL. The instrument of choice for this purpose, the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), comprising 10 meticulously designed items showing a robust correlation with HRQoL in patients with IBD, was used to evaluate HRQoL (score 10 to 70, poor to good QoL).^12,13 The SIBDQ is a self-reported survey designed to assess the impact of IBD on four aspects of HRQoL: bowel symptoms (three items: abdominal pain, flatulence, and urge to defecate), systemic symptoms (two items: fatigue and weight maintenance), emotional function (three items: depression, stress, and anger), and social function (two items: frequency of canceling and being limited in social activities).^13,14

The objective of this study is to explore the interplay between diverse clinical factors and SIBDQ scores, conduct follow-up assessments of SIBDQ scores, and contribute to more effective monitoring and enhancement of QoL in patients with IBD.

1. Patients

We started constructing the IBD cohort in April 2017 and recruited all patients who attended the IBD Clinic at Seoul National University Bundang Hospital (Seongnam, South Korea). This prospective study comprised a cohort of patients with UC and CD, all of whom completed the SIBDQ at the time of enrollment. This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB number: B-1701-380-303). All participants provided written informed consent.

2. Data collection and definitions

The SIBDQ is a disease-specific HRQoL instrument that measures four domains, namely bowel-related, emotional, social, and general well-being, using ten items (Supplementary Table 1). The survey aimed to identify symptoms and outcomes important to patients with IBD in their daily lives and during outpatient clinic visits using a 7-point scale from 1 to 7 for each item. The absolute SIBDQ score ranges from 10 to 70, with higher scores indicating a better QoL. We obtained data of the baseline clinical characteristics of the patients, including age, sex, smoking status, date of diagnosis, comorbidities, IBD subtype, and current and previous medications, by reviewing patient medical records. The partial Mayo Clinic Score and Crohn’s Disease Activity Index (CDAI) were obtained from patients with UC and CD, respectively. As an item of Patient Reported Outcome 2, diarrhea in patients with CD was classified into three categories according to the number of defecations of liquid or very soft stools: no diarrhea, one or two diarrhea episodes a day, and more than three diarrhea episodes a day. Drug history included medications used at the beginning of enrollment and previously used medications. In addition, we conducted a second SIBDQ survey of patients who visited our clinic between November 2021 and April 2022. We then investigated changes in the SIBDQ score and baseline clinical characteristics.

3. Statistical analysis

Statistical analyses were conducted using the PASW software (version 22.0; IBM Corp., Armonk, NY, USA). The association between the SIBDQ score and various clinical factors was assessed using multiple linear regression analyses. The factors significantly correlated with the SIBDQ scores were identified using the Pearson correlation, and nonparametric multiple comparisons of SIBDQ scores among categories were conducted using the Kruskal-Wallis and Mann-Whitney tests. A p-value <0.05 was deemed statistically significant. The statistical methods used in this study underwent review by the Medical Research Collaborating Center at the Seoul National University Bundang Hospital.

1. Demographic and clinical characteristics of patients

One thousand and twenty patients with IBD (UC, 67%; CD, 33%) were enrolled. The basic characteristics of these patients are presented in Table 1. The stool frequencies of patients with UC were 0 in 51%; 1, 29%; 2, 11%; and 3, 9%. Among patients with UC, 59% had a rectal bleeding score of 0, 30% had a Physician Global Assessment (PGA) score of 1, 10% had a PGA score of 2, and 0% had a PGA score of 3. In patients with CD, the clinical manifestations were assessed using the Patient Reported Outcome 2 items: number of daily diarrhea episodes and abdominal pain scores. Most patients experienced 0 to 1–2 episodes of diarrhea per day (86%), whereas a notable proportion reported an abdominal pain score of 0–1, indicating a milder spectrum of symptoms. The mean CDAI score was 82 (interquartile range, 23.25 to 120), offering a quantitative measure of the overall disease activity.

Table 1 . Demographic and Clinical Characteristics of Patients with IBD.

Variable	UC (n=687)	CD (n=333)
Age, yr	42 (31–53)	31 (21–37)
Male sex	426 (62)	257 (77)
Family history of IBD
Yes	34 (5)	21 (6)
Smoking history
None	437 (64)	221 (65)
Past	151 (22)	61 (18)
Current	99 (14)	60 (17)
Extent of disease
E1	271 (40)
E2	194 (28)
E3	222 (32)
Physician Global Assessment score*
0	279 (39)
1	329 (46)
2	105 (15)
3	3 (0)
Stool frequency score†
0	369 (51)
1	206 (29)
2	75 (11)
3	61 (9)
Rectal bleeding score‡
0	425 (59)
1	215 (30)
2	75 (10)
3	1 (0)
Location of disease
L1		74 (21)
L2		16 (5)
L3		252 (74)
L4		42 (12)
Behavior of disease
B1		211 (62)
B2		57 (17)
B3		74 (21)
Perianal		146 (43)
No. of diarrhea, mean
0/day		203 (59)
1–2/day		91 (27)
>3/day		48 (14)
Abdominal pain score§
0		194 (51)
1		120 (32)
2		23 (6)
3		5 (1)
Crohn's Disease Activity Index		82 (23.25–120)
Fecal calprotectin
>250 μg/g	376 (53)	217 (67)
C-relative protein test
>0.5 mg/dL	84 (12)	125 (33)
Extraintestinal manifestation
Joint	88 (12)	46 (13)
Skin	62 (9)	46 (13)
Eye	22 (3)	8 (2)
Any	146 (20)	85 (25)
Current treatment modalities
Corticosteroids	79 (11)	35 (10)
Immunomodulators	91 (13)	86 (25)
Biologics	122 (17)	117 (34)
Exposed treatment modalities
Corticosteroids	438 (61)	265 (77)
Immunomodulators	224 (31)	326 (95)
Biologics	197 (28)	221 (65)

Data are presented as mean (interquartile range) or number (%)..

IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease..

*Physician Global Assessment score 0=normal, 1=mild, 2=moderate, 3=severe; ^†Stool frequency score, 0=normal, 1=1–2 per day more than normal, 2, 3–4 per day more than normal, 3=5 per day more than normal; ^‡Rectal bleeding score, 0=no blood seen, 1=streaks of blood less than half the time, 2=obvious blood most of the time, 3=blood passes alone; ^§Abdominal pain score, 0=none, 1=mild, 2=moderate, 3=severe..

Fecal calprotectin and C-relative protein were used as inflammatory biomarkers, and 53% and 67% of patients with UC and CD exhibited fecal calprotectin levels >250 μg/g, whereas 12% and 33% of patients with UC and CD exhibited C-relative protein levels >0.5 mg/dL, respectively. Extraintestinal manifestations were observed in 20% and 25% of the patients with UC and CD, respectively, indicating that both diseases can manifest in systems other than the gastrointestinal tract.

Current treatment modalities for UC included corticosteroids (11%), immunomodulators (13%), and biologics (17%). Similarly, treatment modalities for CD included corticosteroids (10%), immunomodulators (25%), and biologics (34%). Over the course of the disease, a significant proportion of patients with UC (61%) and CD (77%) were administered corticosteroids. The immunomodulator exposure rate was 31% for UC and 95% for CD, being notably higher for CD. The biologic exposure rates were 28% and 65% for patients with UC and CD, respectively.

2. SIBDQ score analysis on IBD patients

The median score of the first SIBDQ completed after study enrollment was 52 (interquartile range, 44 to 59) (Supplementary Table 1). For patients with UC, the SIBDQ scores across individual questions (Q1 to Q10) ranged from 4.14 to 5.69, with a total score of 50.44. In comparison, patients with CD exhibited slightly higher scores ranging from 4.06 to 5.56 for individual questions and a total score of 51.31 (Table 2). Items 3 (feeling nervous and tense) and 5 (feeling fatigued and tired), which are related to systemic symptoms, exhibited a median of four points, lower than that of the other items (Fig. 1). On analyzing patients with UC and CD separately, both diseases showed lower median scores on the Systemic Symptom Questionnaire. No significant difference was found in the total SIBDQ scores between patients with UC and CD (p=0.243) (Supplementary Fig. 1). However, for item 1 (increased frequency of flatulence), patients with UC scored markedly lower than those with CD (p<0.001). The other items (Q2 to Q10) did not show significant differences between patients with UC and CD (Table 2).

Figure 1. Scores for each Short Inflammatory Bowel Disease Questionnaire (SIBDQ) item (1st). Q, question; UC, ulcerative colitis; CD, Crohn’s disease.

Table 2 . Comparison of Mean Scores for Each SIBDQ Questionnaire between UC Patients and CD Patients.

SIBDQ 1st	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9	Q10	Total
UC	5.09	5.33	4.14	5.19	4.17	5.69	5.38	5.22	4.88	5.36	50.44
CD	5.56	5.37	4.36	5.27	4.06	5.63	5.37	5.33	5.06	5.29	51.31
p-value	<0.001	0.752	0.059	0.449	0.337	0.548	0.927	0.299	0.082	0.527	0.243

SIBDQ, Short Inflammatory Bowel Disease Questionnaire; Q, question; UC, ulcerative colitis; CD, Crohn’s disease..

3. Factors correlated with the SIBDQ score

In patients with UC, the SIBDQ score was negatively correlated with stool frequency (β=–2.333, p<0.001), PGA (β=–3.950, p<0.001), fecal calprotectin level (β=–4.014, p<0.001), and use of corticosteroids (β=–4.809, p<0.001). In patients with CD, the significant factors that were negatively correlated with the SIBDQ score were number of diarrhea episodes per day (β=–1.467, p=0.024) and CDAI score (β=–0.045, p<0.001) (Table 3).

Table 3 . Factors Correlated with SIBDQ Score among Ulcerative Colitis Patients and Crohn’s Disease Patients.

Variable	β	p-value
Ulcerative colitis
Stool frequency	–2.333	<0.001
PGA score	–3.950	<0.001
FCP	–4.014	<0.001
Corticosteroids use	–4.809	<0.001
Crohn’s disease
Stool frequency	–1.467	0.024
CDAI score	–0.045	<0.001

SIBDQ, Short Inflammatory Bowel Disease Questionnaire; PGA, Physician Global Assessment; FCP, fecal calprotectin; CDAI, Crohn's Disease Activity Index..

Dependent variable: SIBDQ score; Regression coefficients of variables used in multiple linear regression..

4. Changes in SIBDQ score among patients with UC and CD

The follow-up SIBDQ score was measured for 202 patients over a median time of 3.6 years (interquartile range, 2.7 to 4.3 years) from the initial SIBDQ questionnaire test. Among the patients with UC, 33 (26.4%) showed a decrease of ≥10% in the SIBDQ score on the second administration of the questionnaire, whereas 34 (27.2%) showed an increase of ≤10% (Table 4). Additionally, 58 patients (46.4%) had a ≥10% increase in the SIBDQ score. In contrast, among patients with CD, 24 (31.1%) experienced a decrease of ≥10% in their SIBDQ scores during the second administration of the questionnaire. Further, 24 patients (31.1%) showed a decrease of <10% or an increase of <10%. Meanwhile, 29 patients (37.8%) had an increase in the SIBDQ score of ≥10%.

Table 4 . Comparison of the Change in Score between the 1st and 2nd SIBDQ among UC and CD Patients.

	SIDBQ 1st score → SIDBQ 2nd score	No. (%)
UC	Reduced over 10%	33 (26.4)
	Less than 10% reduction to less than 10% increase	34 (27.2)
	Over 10% increase	58 (46.4)
CD	Reduced over 10%	24 (31.1)
	Less than 10% reduction to less than 10% increase	24 (31.1)
	Over 10% increase	29 (37.8)

SIBDQ, Short Inflammatory Bowel Disease Questionnaire; UC, ulcerative colitis; CD, Crohn’s disease..

There was no significant difference in the first and follow-up SIBDQ scores between patients with UC and CD (p=0.243) (Fig. 2). On comparing the scores of each item of the first SIBDQ score, items 3 and 5 had relatively low scores. This pattern was also observed in follow-up SIBDQ results.

Figure 2. Scores for each Short Inflammatory Bowel Disease Questionnaire (SIBDQ) item (2nd). Q, question; UC, ulcerative colitis; CD, Crohn’s disease.

This study investigated the demographic, clinical, and QoL-related characteristics of 1,020 patients with IBD. The patients exhibited diverse characteristics, including age, sex distribution, disease extent, and symptoms. The SIBDQ scores revealed comparable overall QoL aspects, although specific symptoms differed, such as increased frequency of flatulence in UC. Factors correlating with lower SIBDQ scores differed between UC (higher stool frequency, physician assessment, calprotectin levels, and corticosteroid use) and CD (daily episodes of diarrhea and CDAI scores). Min Ho et al.¹⁴ studied the HRQoL of IBD patients using the SIBDQ. They identified factors that significantly worsened HRQoL, including the presence of active disease, corticosteroid use, poor medication adherence, and the presence of extraintestinal manifestations. In our study, we found a similar result with a correlation between corticosteroid use and HRQoL in UC patients. However, unlike their findings, our study did not find a correlation between the presence of extraintestinal manifestation and HRQoL, highlighting a difference.

The changes in SIBDQ scores over time reflect the dynamic nature of QoL in IBD patients. The observed improvements in a significant portion of the cohort (43%) over a 3-year follow-up suggest that appropriate clinical management can positively impact patient QoL. However, the persistence of low scores related to systemic symptoms such as fatigue and tension underscores the need for comprehensive treatment approaches addressing both physical and psychological aspects of IBD. In addition, the observed distribution of SIBDQ changes emphasized the tool’s capacity to capture the evolving nature of the patient’s experience over time. This temporal aspect emphasizes the role of SIBDQ in facilitating adaptive and individualized management strategies that align with the changing needs and challenges faced by individuals with IBD throughout their lifetime.

A particularly noteworthy finding is the consistent observation of low scores related to tension and fatigue across both survey periods. These findings underscore the importance of adopting a holistic approach for the treatment of IBD. Fatigue is a highly prevalent and incapacitating symptom of IBD.¹⁵ Approximately 80% and 50% of patients with active and inactive IBD, respectively, reported significant fatigue, which significantly compromises HRQoL. A significant proportion of people with IBD (up to 51%) experience fatigue and lack of energy for daily activities, preventing them from going to work.^16-19 Limited estimates exist regarding the direct expenses associated with fatigue in IBD patients; however, a 2007 survey in the United States general population projected an annual excess direct and indirect cost associated with fatigue exceeding US$100 billion.¹⁶ The etiology of fatigue in IBD is likely multifactorial and encompasses various components.¹⁷ While certain contributing factors like nutritional deficiency or active inflammation may be modified through intervention, fatigue often persists in the absence of these factors, and its origin remains unexplained in numerous cases.¹⁸ Despite the high prevalence and impact of fatigue in individuals with IBD, much remains unclear. Fundamental research on the pathophysiological basis of fatigue in chronic inflammation urgently requires attention. The multidimensional nature of influential factors suggests that the mechanism of fatigue may vary among patients, potentially leading to different subtypes of fatigue within the IBD population.²⁰ Some individuals with fatigue may respond favorably to microbiome-targeted therapies, whereas others may benefit from physical activity interventions or behavioral therapy.^21-23 Over the last ten years, a significant portion of IBD research has concentrated on developing new therapies targeting immune pathways and assessing their impact on disease activity. However, research on interventions for managing fatigue in patients with IBD is limited, except for studies on behavioral modifications. There is a crucial need for future clinical trials assessing a variety of pharmacological and non-pharmacological approaches alongside comparative efficacy research. Educating both patients and medical practitioners about the prevalence and impact of fatigue is critical to ensure collaborative efforts in addressing this debilitating and frequently overlooked symptom.

This study revealed that, unlike that in patients with CD, flatulence significantly impacts the QoL in individuals with UC. The most plausible hypothesis is that of microbial production being associated with the development of mucosal inflammation in UC. The microbial synthesis of gaseous metabolites, such as nitric oxide and hydrogen sulfide, is involved in mucosal inflammation development in UC.²⁴ At the cellular level, exposure of the colonic epithelium to high concentrations of these gases promotes the functional defects observed in UC. Despite the limited available evidence, epidemiological and clinical data suggest the idea of mitigating mucosal inflammation in UC through dietary approaches that target the reduction of hydrogen sulfide.²² Establishing therapeutic approaches through research on sulfide-reducing dietary therapy and similar interventions could improve the QoL of UC patients.

The uniqueness of this study is underscored by its rarity: a SIBDQ-based follow-up study involving a substantial cohort exceeding 1,000 patients with IBD, systematically tracked over a duration of more than a year. This comprehensive approach ensures a robust dataset for analysis and provides insights into the trends and changes in patient outcomes over time. By quantifying the QoL of patients with IBD using the SIBDQ questionnaire and examining its correlation with diverse clinical factors, this study enhances our understanding of the qualitative and quantitative dimensions of the impact of IBD. Furthermore, this study clarified symptom-related trends in patients with UC and CD by comparing the SIBDQ sub-items. This analysis provides valuable insights for determining medical approaches and patient management strategies aimed at improving the QoL of individuals with IBD.

However, this study has several limitations. It did not explore the impact of socioeconomic factors on QoL in patients with IBD. Economic constraints, healthcare access, and social support networks can significantly influence well-being but have not been explicitly addressed. Additionally, the SIBDQ may not capture all aspects of QoL relevant to patients with IBD. Moreover, it relies on self-reported data from patients, which may be subject to recall bias or differences in interpretation. In our study, because the psychological status of the patients was not investigated, the psychological pathways underlying correlations between clinical factors and SIBDQ scores could not be clarified. We cannot rule out the possibility that psychological factors such as anxiety and depression mediated the influence of clinical factors on SIBDQ scores. Graff et al.²⁵ proposed that treatments for IBD might be linked to anxiety and depression, with the latter potentially leading to a reduced QoL in affected individuals compared to those without depression. Farbod et al.²⁶ corroborated other studies, indicating that depression may have a more significant impact on HRQoL than disease activity alone, using the Beck Depression Inventory-II to predict SIBDQ scores. Among psychosocial factors, psychological distress and QoL are the most influential in non-adherence.²⁷ Future research should investigate the combined effects of disease activity and mood disorders on HRQoL in IBD patients.

In conclusion, this prospective study utilizing the SIBDQ involving 1,020 patients with IBD revealed significant correlations between bowel movement-related issues and lower HRQoL in patients with UC and CD. After a 3-year follow-up, 43% of patients experienced an improvement in their QoL. Among the SIBDQ items, the score for the item related to fatigue was consistently low, highlighting the prevalence of fatigue as a major concern in patients with IBD.

No potential conflict of interest relevant to this article was reported.

Study concept and design: S.K., H.Y. Data acquisition: S.K. Data analysis and interpretation: S.K. Drafting of the manuscript: S.K., H.Y. Critical revision of the manuscript for important intellectual content: S.K., Y.K.J., Y.C., C.M.S., Y.S.P., N.K., D.H.L., H.Y. Statistical analysis: S.K. Administrative, technical, or material support; study supervision: S.K., H.Y. Approval of final manuscript: all authors.

Supplementary materials can be accessed at https://doi.org/10.5009/gnl240172.