Inflammatory bowel disease (IBD) is a disorder associated with chronic inflammation and immune dysregulation, therefore, patients with this chronic pathology may be particularly prone to such physiological factor as frailty. Despite developing awareness of frailty, it remains understudied in the patients with IBD. According to scientific studies, frailty is an independent and significant risk factor for adverse clinical outcomes in this patient population (Huang et al., 2022; Li et al., 2022). Regardless of age, this condition increases the risk of postoperative complications, re-hospitalizations, and mortality, and also reduces the body's resistance to infections. The scientific community increasingly frequently pays attention to the connection between IBD and frailty, namely its negative prognostic impact. In particular, Silvia Salvatori and co-authors claim that according to the data of their descriptive cohort study on a sample of 386 outpatients with IBD (198 with Crohn's disease and 188 with ulcerative colitis), frailty can be documented in almost one-fifth (about 20%) of the patients with IBD (Salvatori et al., 2023). According to another study, screening for frailty showed that 23% of patients with IBD had increased vulnerability and 44% of patients had functional impairment (Simon et al., 2023). The authors recommend considering the active stage of the disease as an independent predictor of the frailty phenotype. The data from a recently conducted meta-analysis by Huang, X et al. has showed that the frailty becomes increasingly common among patients with IBD and is an independent predictor of premature mortality in this patients population. In this study, nine studies were analyzed, involving a total of approximately 1.5 million patients with IBD. The rate of frailty prevalence among the examined patients constituted 18%. In their works, the authors emphasized the need to introduce screening for this condition, particularly to establish optimal, standardized criteria for its assessment and diagnosis (Huang et al., 2022).
The Clinical Frailty Scale (CFS) was originally developed for the use in the gerontological population (Rockwood et al., 2005/2007). However, in this study, it is used to assess general physical vulnerability and predict the risk of adverse clinical outcomes in adult patients with IBD at the age of 18 to 65 years (Rockwood et al., 2005). The use of the CFS in this younger age cohort is justified by its multi-domain nature, which allows for a combined assessment of the patient's physical function, somatic reserve, and cognitive level. Although there is limited scientific data on age-stratified frailty phenotype assessment, available results suggest an increasing tendency of frailty in case of IBD with two peaks, namely at the age of 60–69 and at the age of 18–29. And if the first one is a classic frailty caused by age, the second one is due to the disease severity and activity. These results indicate that IBD is a factor that accelerates aging, so the need for its screening is appropriate, especially at a young age. As a matter of fact, IBD is associated with weight loss, hypoalbuminemia, sarcopenia, and rapid fatigue regardless of the patients' age. These conditions contribute to the disruption of the body's physical functions and have a negative impact on the QofL of this category of patients (Salvatori et al., 2023). There is also growing evidence in the scientific literature that frailty is most amenable to intervention in its early stages, making its detection advisable at the onset of the disease. It is worth noting that the use of CFS in this non-traditional age group is adaptive because, in the patient cohort we have examined, frailty is a manifestation of accumulating deficiencies, rather than simply aging. The obtained results will be subject to careful interpretation, taking into account this methodological feature. In order to ensure diagnostic validity and reliability of the results, the CFS vulnerability assessment is conducted simultaneously with other standardized instruments that measure the key aspects of the patient's condition. They include The Cumulative Illness Rating Scale (CIRS) (Linn B.S. at al., 1968) providing an opportunity to assess objectively the burden of comorbidities, namely the number of chronic diseases and their severity (Rockwood et al., 2020) and the “General Health Questionnaire”-Medical Outcomes Study Short-Form 36 (MOS SF-36), as a valid tool for quantitative assessment of the health-related quality of life (HRQOL). This approach is of key importance for studying the complex relation between the IBD clinical course, vulnerability level, the presence of comorbidities, and HRQOL indicators (Romash et al., 2022; Trishch et al., 2025).
It is hypothesized that early and meaningful assessment of frailty in patients with IBD will provide an opportunity to improve diagnosis and personalize treatment protocols, and therefore improve the QoL of such patients.
The objective of the study was to evaluate the possibilities of the adapted use of the “Clinical Frailty Scale” in adult patients with inflammatory bowel diseases by verifying its prognostic significance in comparison with the comorbidity level and indicators of quality of life.
The study included 248 patients with IBD who received medical care in medical facilities in Ivano-Frankivsk. Patients were divided into two groups. Group I included 117 patients with Crohn's Disease (CD) (mean age constituted 40.32±21.74 years) and Group II comprised 131 patients with ulcerative colitis (UC) (mean age was 43.34±21.57 years). The control group consisted of 82 apparently healthy volunteers without a family medical history of IBD, representative in terms of age and sex.
Analysis of gender distribution showed differences between nosological groups partially correlating with global epidemiological data on IBD. A slight predominance of women was observed in the group of patients with CD comprising 54.7% (64 individuals), while men constituted 45.3% (53 people). However, men clearly dominated among the patients with IBD constituting 59.5% (78 people), while the share of women was 40.5% (53 people).
The diagnosis of IBD, CD or UC was made on the basis of clinical, laboratory, radiological and endoscopic criteria in accordance with the Unified clinical protocol of primary and specialized medical care “Inflammatory bowel diseases (Crohn's disease, ulcerative colitis)” (approved by the Order of the Ministry of Health of Ukraine No. 1742 dated 6.10.2023) and clinical guidelines (CG) “Inflammatory bowel diseases” and “Treatment of Crohn's disease in adults”. These Clinical Guidelines are an adaptation of the Clinical Guidelines “Evidence-based clinical practice guidelines for inflammatory bowel disease, 2020” for the health care system of Ukraine.
In order to achieve the purpose of the study, the following methods were used: the assessment of functional reserve and frailty by means of “Clinical Frailty Scale” (CFS); the assessment of comorbidity and its severity by means of “The Cumulative Illness Rating Scale” - CIRS (Rockwood et al., 2020; Linn et al., 1968).
Thus, the CFS scale is a prognostic tool for assessing physiological reserve and adverse outcomes risk. It classifies people according to their functional reserve and the degree of dependence in performing daily life activities. It was originally developed as a 7-point ordinal scale, but in 2020, it was transformed into a 9-point scale with the addition of two levels, updated names for the levels, and changes to their descriptions (Rockwood et al., 2005/2020). The nine-level version of the CFS scale classifies the categories of patients' functional status and frailty from 1 “Very high functional capacity” to 9 “Terminal state” (Fig. 1). A physician performs evaluation based on a physical examination and case history, including the patient's functional status for the past two weeks. According to this assessment tool, patients with very high functional capacity (Very Fit) are distinguished. Individuals with optimal physical and psychosocial reserve belong here. High physical activity (regular exercise) and high functional status are normal for them. Individuals with good functional capacity (Well) are characterized by the absence of clinically active diseases; however, their level of physical reserve is significantly lower compared to the first category, and physical activity is irregular, episodic, or seasonal. In the group of patients with well-controlled diseases (Managing Well), patients' chronic diseases are well managed, with activity levels limited to basic mobility (routine walking) and no regular physical activity outside of this routine. The category of individuals whose independence in basic daily activities is preserved, but whose functional reserve is significantly reduced (inhibition and/or daytime fatigue), belongs to the category of vulnerable (Vulnerable). Mild Frail is characterized by an obvious slowing of motor activity, a progressive deterioration of independence and the need for assistance to perform both complex (finances, transportation, general cleaning) and basic (shopping, cooking) activities in everyday life. Moderate Frail is manifested by the appearance of difficulties in performing basic daily activities. Such patients demonstrate dependence on external assistance for all types of activity outside the home and in household chores (difficulty with stairs, the need for assistance when bathing, dressing). There is a need for minimal external support and supervision. Severe Frail is defined as complete dependence on assistance for personal care and basic daily activities (regardless of physical or cognitive etiology), while maintaining clinical stability and a relatively low risk of short-term mortality. Very Severe Frail is characterized by a state of complete dependence, the lack of ability to recover even after minimal stressful events, such as a minor illness. Terminally Ill is a category applied to patients with a diagnosed condition that has a limited survival prognosis (less than 6 months) and who are not necessarily frail by other criteria of the scale.
Categorization of patients according to the Clinical Frailty Scale (CFS; Rockwood et al., 2005/2007) for risk stratification.
In order to facilitate statistical analysis and risk stratification, the patients were evaluated according to the 9-level CFS scale and categorized into three clinically meaningful groups (Figure 1): “Strong” (1–3 points according to CFS scores), “Vulnerable” (4 points according to CFS score), and “Frail” (≥5 points according to CFS score). Numerous professional scientific publications testify to the expediency of such categorization, namely establishing a “threshold” of CFS≥5 as a generally accepted marker to designate patients of the “Frail” category and the selection of a separate category of CFS 4, namely “Vulnerable” as critical one in order to designate patients who already have a reduced physiological reserve, but are not yet frail (the risk group) (Huang et al., 2022; Fons et al., 2023; Amon et al., 2022)
It is important to note that the CFS score reflects the baseline functioning level of the examined patients, and not just their condition at the time of treatment. The principle of judgment-based scaling allows it to be adapted to the unique profile of patients with IBD (taking into account chronic fatigue, disease-related deficiencies, and psychosocial impact) (Huang et al., 2022).
Based on the data of the Cumulative Illness Rating Scale, the following three indices were evaluated: Cumulative Illness Rating Scale – Total Score, CIRS-TS; Comorbidity Index (Cumulative Illness Rating Scale-Comorbidity Index, CIRS-CI); Index of Severity (Cumulative Illness Rating Scale-Severity Index, CIRS-IS). The use of these three indices enables the assessment of the patient's general condition from multiple perspectives. CIRS-TS is the sum of scores for 14 systems. CIRS-CI reflects the level of comorbidity, namely the number of organ systems in which at least one disease with a score of ≥2 is recorded, that is, how many systems have clinically significant diseases. In turn, CIRS-IS represents the overall severity of the somatic burden, shows how severe these diseases are (Romash et al., 2023; Di Raimondo et al., 2023).
The expediency of comparing the Clinical Frailty Scale and the Cumulative Illness Rating Scale (CIRS) is that these instruments assess different but complementary aspects of general health and together present complete information about patient's vulnerability. By using two scales simultaneously, we will ensure the integrality of the assessment by combining two the most important aspects of vulnerability: the structural one (what's wrong?) – measured by CIRS – how many diseases the patient has and how severe they are and the functional one (how does it affect?) – measured by CFS – how this burden of diseases affects their general reserve and quality of life. The Charlson Comorbidity Index (CCI) was also calculated for all patients included in the study. It is a prognostic index that provides an opportunity to assess the impact of comorbidity on 10-year survival.
The MOS SF-36 questionnaire (Medical Outcomes Study Short-Form 36) was developed by J.E. Ware et al. It is the most common non-specific means of studying the QofL in patients providing an opportunity to evaluate various components of the patient's life associated with the disease. The SF-36 questionnaire is a standardized tool for assessing quality of life, consisting of 36 questions integrated into eight main scales (concepts) of health (Fig. 2). The MOS SF-36 scale is a multidimensional instrument designed to quantify a patient's subjective perception of their HRQOL. It covers eight distinct domains: physical functioning, social role functioning, role limitations due to physical and emotional problems, mental health, measures of vitality and bodily pain, and general health perception. The score for each domain is standardized between 0 (the worst state) and 100 (the best state). The integration of these indicators makes it possible to form two key generalized scales: the scale of physical health and the scale of mental health. Such structure provides comprehensive monitoring of clinical studies, reflecting the impact of the patient's health state on both functional capabilities and psychoemotional well-being.
The structure of physical and psychological components of health according to the scales of the SF-36 questionnaire.
Statistical data processing was performed using the Microsoft Excel 2016 software. A Student's t-test was used to compare the groups. Quantitative characteristics were presented as the arithmetic mean (M) with standard error (±m). The reliability of the indicators was determined at the level of statistical significance (p<0.05).
The analysis of patient distribution by gender detected that women predominated among patients with CD, constituting 54.7% (64 individuals), while men comprised 45.3% (53 individuals). Men predominated among patients with UC, accounting for 59.5% (78 individuals), while women comprised 40.5% (53 individuals).
The indicators obtained based on the evaluation of the data according to the Clinical Frailty Scale (CFS) showed a significant difference in functional reserve between the patients in the experimental and control groups (Table 1; Figs. 3 and 4).
Comparative characteristics of the functional reserve and the degree of dependence of the examined patients according to the data of the “Clinical Frailty Scale” (Rockwood et al., 2005/2007).
| CFS scale scores | Group I n=117 | Group by functional status | Group II n=131 | Control group n=82 |
|---|---|---|---|---|
| 1–3 | 42 (35.8%) | Strong | 53 (40.5%) | 80 (97.6%) |
| 4 | 67 (57.3%) | Vulnerable | 72 (54.9%) | 2(2.4%) |
| 5–9 | 8 (6.9%) | Frail | 6 (4.6%) |
Distribution of the examined patients according to the stratification groups of the “Clinical Frailty Scale” (Rockwood et al., 2005/2007).
The ratio of the mean scores according to the “Clinical Frailty Scale” (Rockwood et al., 2005/2007) in the examined patients.
Notes:
*– (p<0.05) the data are reliable relative to the indicators of the control group.
# - (p<0.05) the data are reliable between the research groups.
According to the data presented in Table 1, 42 patients (35.8%) of Group I and 53 patients (40.5%) of Group II belonged to the category with strong physiological reserve (CFS ≤3). At that time, more than half of the patients in Group I (67 people, 57.3%) and Group II (72 people, 54.9%) belonged to the “vulnerable” category (CFS=4), indicating a decrease in functional reserve. CFS-4 means that the patient is usually independent of assistance but is slow and tired during the day, and has reduced physical activity. This condition is a direct sign of the systemic effect of chronic inflammation in IBD, which depletes the body's reserves, turning physiologically “strong” patients into “vulnerable” ones. This category is the major one for early interventions. Frailty (≥5 points) was found exclusively among patients with IBD, constituting 6.9% in Group I and 4.6% in Group II (p<0.001), whereas “Frail” patients were not identified in the Control group (Figure 3).
According to Figure 4, the average CFS score in Group I was 3.1 ± 1.2 points, whereas it was significantly higher in Group II constituting 4.2 ± 0.6 points (p<0.05). In the Control group, the mean CFS score was 2.1 ± 0.97 points.
Thus, the average level of functional vulnerability in the patients with CD was approximately 1.5 times higher, and 2.0 times higher in patients with UC compared to the Control group (p<0.05).
The assessment of the comorbid profile according to the CIRS scale (Table 2) confirmed a significantly burdened condition of patients with IBD compared to the Control group.
Comparative characteristics of the average indicators of the “Cumulative Illness Rating Scale” (Linn B.S. at. al., 1968) and the “The Charlson Index” (Charlson, M. E. at. al., 1987) in the examined patients.
| Indicators | Group I, n=117 | Group II, n=131 | Control group, n=82 |
|---|---|---|---|
| CIRS-CI | 2.5 (1.0–3.5)* | 2.1 (1.2–2.7)*# | 1.0 (0.98–2.01) |
| CIRS-IS | 1.93 (1.48–2.97)* | 1.75 (1.27–2.48)*# | 1.12 (0.5–1.5) |
| CCI | 3.14 (2.0–4.0)* | 2.93 (2.0–3.0)*# | 1.69 (1.0–2.0) |
Notes:
*– (p<0.05) the data are reliable relative to the indicators of the control group.
# - (p<0.05) the data are reliable between the research groups.
The mean index of disease severity (CIRS-IS) was significantly higher in patients with IBD constituting 1.93 points in Group I and 1.75 points in Group II, compared to 1.12 points in the Control group (p1,2<0.005). The disease comorbidity index (CIRS-CI) was also higher in patients with IBD: the mean value of the indicator was 2.5 points in Group I and 2.1 points in Group II, compared to 1.0 points in the Control group (p1,2<0.005), indicating the presence of mild to moderate diseases requiring ongoing treatment.
According to the presented data (Table 2), the CCI index in Group I averaged 3.14 ± 0.27 points, whereas in Group II, it was 2.93 ± 0.14 (p ≤ 0.005).
According to the data presented in Figure 5, the most pronounced changes in the physical component of QOL in the examined patients were observed on the general health (GH) scale.
Indicators of QofL (physical component of health) in patients with IBD
Notes:
*– (p<0.05) the data are reliable relative to the indicators of the control group.
The average value of GH indicators in Group I (51.81±1.23 points) and Group II (53.86±1.97 points) was lower compared to the control group (74.5±1.94; p<0.05). A significant deterioration of indicators related to functional limitations and pain syndrome was also established. The average value of bodily pain (BP) index was 60.24±0.83 points in the patients with CK, and 61.9±1.97 points in the patients with UC, which was 28.88% and 26.91% lower than in the control group, respectively (84.7±2.31; p<0.05). The scale of role physical functioning (RP) also showed a statistically significant decrease, namely 58.31±2.01 points (Group I) and 56.9±0.79 points (Group II), compared to 85.3±1.62 points in the Control group (p<0.05). The indicators of physical functioning (PF) were reduced to 61.3±1.43 points (Group I) and 61.02±1.03 (Group II) compared to 97.8±2.14 points in the Control group.
Regarding the mental health component (Fig. 6), the mental health (MH) domain decreased by more than half in patients with CD (31.5 ± 1.01) and UC (32.38 ± 0.79) compared to the Control group (75.8 ± 3.97; p<0.05). This indicated a high risk of affective disorders development. Vitality/Fatigue (VT), i.e. an indicator reflecting the level of energy and adaptive reserves, also decreased significantly, namely to 43.22±1.32 points in the Group I and to 42.03±2.64 points in the Group II. The decrease in both indicators was statistically significant compared to the Control group (80.78 ± 3.79; p<0.05). The average score of role-emotional functioning (RE) significantly decreased in both experimental groups, constituting 57.6±1.03 and 54.7±1.33, respectively, which was 1.3 and 1.4 times lower than in the Control group (76.7±2.84; p<0.05). Indicators of social functioning (SF) in patients with IBD were 53.21±1.49 and 56.32±1.38, which were 1.6 and 1.5 times lower than those of the Control group (83.78±2.31; p<0.05).
Indicators of QofL (mental component of health) in patients with IBD.
Notes:
*– (p<0.05) the data are reliable relative to the indicators of the control group.
According to the correlation analysis (Table 3), a significant positive relation was found between the indicators of the structural burden of the disease (CIRS-CI, CIRS-IS, CCI) and the body's functional reserve (CFS). Thus, structural vulnerability, namely its quantitative (CIRS-CI) and qualitative (CIRS-IS) aspects, was the main link in the pathogenesis of functional reserve (CFS) in patients with IBD. The highest correlation coefficient with CFS indicators was observed in CCI suggesting it to be considered as a reliable marker of weakness in patients with IBD.
The results of the correlation analysis between the indicators of the “Cumulative Illness Rating Scale” (Linn B.S. at. al., 1968) and the “Charlson Index” (Charlson, M. E. at. al., 1987) and the indicators of the “Clinical Frailty Scale” (Rockwood et al., 2005/2007) in the examined patients.
| Indicates of the CFS | examined patients | Indicators of the CIRS scale: CIRS-CI/CIRS-IS | CCI | |
| Group I, n=117 | 0.584*** | 0.678*** | 0.692*** | |
| Group II, n=131 | 0.601*** | 0.715*** | 0.725*** | |
| Control Group, n=82 | 0.295* | 0.334** | 0.341** | |
Notes:
- weak correlation (p>0.05);
- moderate correlation (p<0.05);
- strong correlation (p<0.05).
The data obtained by us regarding the gender distribution in IBD are partially comparable with global trends. According to the trends, CD is characterized by a slight predominance of women in most Western countries, while in Eastern countries, men are more affected. However, the gender distribution in case of UC is almost equal (Liu et al., 2023). Although some studies show a slight predominance of men in case of UC, especially after the age of 40 (Goodman et al, 2020).
A high proportion of patients classified as “vulnerable” indicated a significant decrease in functional reserve in the examined patients with IBD. This condition is considered to be a direct sign of systemic effects of chronic inflammation inherent in IBD, which depletes the body's reserves, turning physiologically “strong” patients into “vulnerable”. CFS=4 is a main target for early interventions as it reflects the onset of clinically significant functional deficiencies. The high prevalence of vulnerability and frailty detected in the examined patients with IBD clearly proved the negative impact of chronic inflammation on the general functional state and body stability (Li et al., 2024). The obtained results are partially consistent with recent international studies by Salvatori et al., Huang et al., and Liu et al. In particular, according to the works of Salvatori S. et al., a frail phenotype and a pre-frail phenotype were diagnosed in 17% and 28% of patients with IBD, which was quite high for this category of patients, whose average age was 47 years (Huang et al., 2022; Salvatori et al., 2023; Liu et al., 2023).
Higher CIRS-CI scores in Groups I and II indicated medical complexity and comorbidity in case of IBD, and a significant statistical difference provided strong evidence that IBD was associated with a greater comorbidity burden and severity. The results obtained by us are partially comparable with the latest international scientific data (Lenti et al., 2025).
In addition, the CCI assessment of comorbidity revealed a statistically significant difference between the groups: the CCI score in the Crohn's Disease Group averaged 3.14±0.27 points, which was significantly higher than that in the Ulcerative Colitis Group, 2.93±0.14 (p≤0.005). Such CCI scores predict 10-year survival ranging from 45 to 79% among patients with CD and 52–79% in case of UC. Our findings, indicating a high level of frailty and a significant burden of comorbidity, are consistent with large cohort studies, including the work of Alexander S. Qian et al., who have found frailty to be an independent predictor of higher mortality in patients with IBD (Lenti et al., 2025), increasing its risk almost threefold (Kochar et al., 2020).
The results of the QofL assessment according to the SF-36 questionnaire confirmed significant functional disorders and reduced physical and mental reserve in the patients with IBD. A decrease in the physical component (GH, BP, RP, PF) indicated a profound negative impact of chronic inflammation on general well-being, body resistance, and the ability to engage in daily physical activity. A particularly significant decrease in BP and RP indicators showed that physical symptoms and pain syndrome were the main limiting factors in these patients' lives. The deterioration of the mental component was even more dramatic. An abrupt, more than twice, drop in MH indicateв a high risk of affective disorders development and the need for psychological support. A significant decrease in VT confirmed pronounced general weakness, increased fatigue, and exhaustion of adaptive reserves, which was typical for chronic inflammatory processes. Decreases in RE and SF further confirmed that psychoemotional discomfort and secondary emotional problems limited both daily activities and social interaction of the patients with IBD. The pronounced deterioration of the mental component of the QofL combined with frailty emphasized the need to use a biopsychosocial approach in the management of the patients with IBD. This corresponded to modern recommendations for integrated care taking into account the “gut-brain axis” (Tsagkaris et al., 2021). Considering the detected psychoemotional disorders caused by chronic inflammation and disease, attention should be also paid to the possible role of dysregulation of neurotransmitters, metalloenzymes, and hormones in response to chronic stress, which is similar to the pathophysiological changes observed in mental disorders (Romash et al., 2025).
The practical implementation of such an integrated approach directly depends on the quality of medical education and the psychological preparedness of future clinicians. In this regard, it is important to understand the motivational factors and challenges that medical students face during their training, as these elements determine their professional resilience and ability to work with complex clinical cases, including patients with IBD (Tymkiv et al., 2025). This issue is further exacerbated by the ongoing Russian-Ukrainian war, which places an unprecedented psychological burden on healthcare and psychosocial support workers, increasing the risk of mental health challenges among those responsible for patient care (Kang et al., 2024). Such environmental stressors necessitate a more robust framework for psychological support and integrated management, not only for patients but also for the medical professionals themselves.
The results of the conducted correlation analysis confirmed that frailty in patients with IBD is a functional consequence of accumulated structural deficiencies and comorbidities, and not just an isolated symptom. Since the burden of comorbidity and the need for multidisciplinary care increase, the integration of such findings into clinical practice requires systemic approaches to health care. This includes the implementation of innovative solutions, particularly artificial intelligence and digital health technologies for personalized monitoring and prediction of disease progression (Rayan et al., 2021; Matiashova et al., 2021).
A significant proportion of adult patients with IBD demonstrated significantly higher indicators of reduced functional reserve compared to the Control group.
The detected vulnerability of the examined patients correlated with a burdened comorbid profile, thus confirming the feasibility of an integrated assessment according to the “Clinical Frailty Scale” for predicting clinical consequences in this cohort.
The results of the QofL assessment according to the SF-36 questionnaire confirmed pronounced functional disorders and reduced physical and mental reserve in the patients with IBD.
The results of the conducted correlation analysis confirmed that frailty in the patients with IBD was a functional consequence of accumulated structural deficiencies and comorbidities, and not just an isolated symptom.
Assessment of disability should be a part of a routine clinical practice in order to optimize the management of patients with IBD aimed at preserving functional reserve and improving their QofL.