Introduction

Fatigue is a significant predictor of worst health-related qualify of life in inflammatory bowel disease (IBD) patients. Nevertheless, the role of fatigue in IBD patients under infliximab (IFX) therapy has been poorly investigated.

Aims & Methods

The aim of the study was to evaluate the potential factors associated with fatigue in patients under maintenance treatment with IFX.
Methods: A prospective observational cohort study was designed. All IBD patients aged 18 and over under maintenance treatment with intravenous (IV) infliximab were consecutively included at the infusion day. Patients completed 3 self-administered questionnaires. Fatigue was assessed with the Fatigue Impact Scale (FIS), quality of life with the Inflammatory Bowel Disease Questionnaire-Short From (IBDQ-9) and anxiety and depression using the Hospital Anxiety and Depression scale (HAD). We considered the maximum total FIS as the highest fatigue perception. Disease activity was defined in Crohn’s disease as a Harvey-Bradshaw index >4, and in ulcerative colitis (UC) as a Partial Mayo index >2. Patient demographics and disease characteristics were also collected: age, sex, disease duration, smoking habit, type of IBD, extra-intestinal manifestations, clinical activity, prior surgery, obesity, anemia, treatments (steroids, immunosuppressants, anxiolytics, antidepressants) and presence of anxiety or depression. Multiple linear regression was used to identify the variables associated with the presence of fatigue.

Results

Ninety patients were consecutively included (49 female, median age 42 years, interquartile range 19). Sixty three patients (70%) had Crohn’s disease (46.8% fistulising and 25.8% stenosing behaviour) and twenty seven ulcerative colitis (30%). Nearly 27% were smokers, 35 (39%) presented anxiety and 18 (21%) depression. Approximately, 8% of the patients and 7% received treatment for anxiety and depression, respectively, but only 2/18 patients with current depression received antidepressants. Combotherapy was present in 41% of the patients and 75.6% were in clinical remission. Mean fatigue was 32.74 ± SD 17.27. The highest scores for fatigue were associated with female gender (B = 10.936; P= 0.009) and the presence of depression (B = 11.114; P = 0.029). Activity disease almost increased significantly the severity of the fatigue(B = 8.995; P= 0.063). The use of antidepressants not increased the risk (B = -4.995; P = 0.555). Patients with fatigue had significantly reduced the quality of life (r = -0.638; p < 0.001).

Conclusion

Uncontrolled depression and female gender increased the risk of severe fatigue more than disease activity in patients under maintenance treatment with IFX. Fatigue is related to worst health-related qualify of life.

Introduction

Environmental factors have only been partially implicated in the aetiopathogenesis of inflammatory bowel disease (IBD). The role of indoor radon, a radioactive gas, has not been formally studied and may play a role in the pathogenesis of the disease.

Aims & Methods

The aim of this study is to analyse the role of individual residential radon exposure on the incidence of IBD in a radon-prone area, also characterised as a high incidence IBD region, and whether this exposure is associated with the development of the disease.
Methods: A case-control study was developed in the health area of Santiago de Compostela (Galicia, Spain) between June 2020 and September 2023, including all consecutive incident cases with IBD. Controls were selected by frequency matching based on sex and age and without IBD. All participants had to have lived in the same home for at least 5 years. All cases were followed up for one year to assess disease progression. Endoscopic index, imaging techniques and analytical parameters were collected. In patients with IBD, hospitalisations related to the disease and the number and severity of flares (measured by Partial Mayo Score and Harvey-Bradshaw) were recorded. Radon levels measured in participants' homes over three months were compared between cases and controls, and between different types of IBD. Each individual was provided with a home radon meter (an RSKS trace detector), which was delivered and read by the Galician Radon Laboratory, a certified radon laboratory. Radon concentrations were categorised into three groups: 0-99 Bq/m3, 100-299 Bq/m3 and >299 Bq/m3. The results are expressed as odds ratios with their 95% CIs obtained by logistic regression.

Results

RADON LEVELS (Bq/m3)	IBD PATIENTS (%)	CONTROLS (%)	OR (95%CI)
0-99	34.3	19.8	1
100-299	45.2	55.8	0.5 (0.3-0.8)
>299	20.5	24.4	0.5 (0.3-0.9)

*OR = Odds Ratio; CI = Confidence Interval.
178 incident cases and 178 controls were included, with a median age of 51 years (IQR 40-59.5). 51.7% were female. 136 IBD patients completed one year of follow-up (78 ulcerative colitis, 52 Crohn's disease and 6 unclassified colitis). The median radon level in the homes of the IBD patients was 144.5 (IQR 83 - 260) and the median radon level in the homes of the controls was 189.5 (IQR 112 - 292.5). After adjustment for age and sex, high radon levels showed a negative association with the development of IBD (taking levels of 0-99 Bq/m3 as reference, OR 100-299 Bq/m3 is 0.5 (95%CI 0.3-0.8) and OR >299 Bq/m3 is 0.5 (95%CI 0.3-0.9). The results are shown in Table 1. Taking into account the different types of IBD, radon levels show the same negative association, but without statistical significance. There were no statistically significant differences in radon levels, taking levels of 0-99 Bq/m3 as reference, between hospitalised and non-hospitalised patients (OR 0.8 95%CI 0.3-2.1 for 100-299 Bq/m3, OR 1. 7 95%CI 0.6-5.0 for >299 Bq/m3), nor in patients with a flare compared with patients without a flare during the follow-up year (OR 0.4 95%CI 0.0-4.5 for 100-299 Bq/m3, OR 5.4 95%CI 0.8-34.3 for >299 Bq/m3). Radon levels were also not associated with the number of flares (OR 0.6 95%CI 0.3-1.7 for 100-299 Bq/m3, OR 1.5 95%CI 0.5-4.5 for >299 Bq/m3). Stratification by type of IBD did not alter the results.

Conclusion

High radon levels may be a protective factor against the development of IBD, and indoor radon levels do not appear to be associated with the development of IBD in terms of hospitalisations or flares.

Introduction

Fatigue is a common but rarely diagnosed symptom in patients with inflammatory bowel disease (IBD). The IBD-specific fatigue questionnaire Inflammatory Bowel Disease Fatigue (IBD-F) was validated in German in 2022. It assesses the severity and frequency of fatigue (Section 1) as well as its impact on daily life (Section 2). The Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) also measures the impact of fatigue on daily life. While the FACIT-F has been validated in English for IBD, it has not yet been validated in German, although it is frequently used in IBD studies.

Aims & Methods

This study compared the IBD-F and FACIT-F in a German-speaking IBD cohort. IBD patients and a healthy control group (HC) completed both the IBD-F and FACIT-F questionnaires. Disease activity in IBD patients was assessed using the partial Mayo Score (pMS for ulcerative colitis; UC) or the Harvey Bradshaw Severity Index (HBSI for Crohn’s disease; CD). Internal consistency was calculated using Cronbach’s α. To assess acceptance, the number of fully completed questionnaires was analyzed. Spearman correlation was used to compare IBD-F and FACIT-F scores in both IBD patients and healthy controls.

Results

A total of 382 IBD patients (CD n = 240; 98 male; age 43.1 ± 13.9; UC n = 142; 72 male; age 43.2 ± 12.6) and 130 healthy controls (HC; 61 male; age 40.2 ± 16.5) participated. 75% (286/382) of the patients reported fatigue in IBD-F Section 1 and were included in further analyses.
Internal consistency was rated as excellent for IBD-F Section 1 (α = 0.930), Section 2 (α = 0.979), and FACIT-F (α = 0.936), as indicated by Cronbach’s alpha. Acceptance decreased with increasing number of items (IBD-F Section 1 94.4%; Section 2 80.1%; FACIT-F 90.9%). A significant negative correlation was observed between the FACIT-F and IBD-F Section 1 in both the IBD group (r_s = -0.751, p < 0.01) and controls (r_s = -0.361, p < 0.01), as well as between the FACIT-F and IBD-F Section 2 (IBD: r_s = -0.862, p < 0.01; HC: r_s = -0.463, p < 0.01).
Patients in remission (59% (168/286)) reported lower fatigue scores in IBD-F Section 1 and 2 and FACIT-F than patients with active disease (36% (104/286)), but higher fatigue scores than HC. HC showed higher fatigue scores in the FACIT-F than in the IBD-F (see Table 1).

Questionnaire	IBD/Controls	N	Mdn (IQR)
IBD-F Section 1 - Total Score	Control IBD - Total - Remissiona - Active diseasea	130 286 168 104	0.0 (2.0) 8.0 (5.0) 6.0 (5.0) 10.0 (6.8)
IBD-F Section 2 - Total Score	Control IBD - Total - Remissiona - Active diseasea	130 286 168 104	0.0 (2.3) 21.0 (28.9) 18.0 (19.0) 30.0 (35.4)
FACIT-F - Total Score	Control IBD - Total - Remissiona - Active diseasea	130 286 168 104	48.0 (7.3) 35.0 (16.7) 37.5 (16.0) 29.6 (19.8)
Mdn = Median; IQR = Interquartile range. a Due to missing data, the pMS and the HBSI could not be calculated for 14 patients. Higher scores in Sections 1 and 2 of the IBD-F, as well as lower scores in the FACIT-F, indicate greater fatigue. IBD-F Section 1 Total Score range: 0–20. IBD-F Section 2 Total Score range: 0–120. FACIT-F Total Score range: 0–52.

Table 1: Descriptive statistics of IBD-F and FACIT-F.

Conclusion

Both the IBD-F and FACIT-F are effective tools for assessing fatigue in IBD patients. The IBD-F, however, appears to better distinguish healthy individuals without fatigue.

Introduction

Lifestyle factors are significant contributors to fatigue, which affects approximately 45% of patients with Inflammatory Bowel Disease (IBD) in remission.

Aims & Methods

In this study, we evaluated the effect of a digital multimodal lifestyle intervention on fatigue in patients with IBD. Patients with IBD in biochemical remission (fecal calprotectin <150 mg/kg) were enrolled in a multicenter, non-randomized, controlled interventional study. The intervention group participated in a 12-month lifestyle program—provided by the non-profit organization Voeding Leeft—that included digital group meetings with a nutritionist and a lifestyle coach focusing on gradual and sustainable behavior change regarding nutrition, physical activity, sleep, and stress management. In addition, the program encouraged patients to exercise more self-control over their personal health. Following the initial six months, attendance at online sessions was not mandatory; however, patients could attend online sessions every six to 12 weeks to stay motivated and foster the lifestyle habits they acquired throughout the course. Patients in the control group received standard care that included an informational leaflet about the potential causes of fatigue in IBD, the leaflet also included basic lifestyle information and advice to exercise more, eat a healthier diet, stop smoking, reduce alcohol intake, improve sleeping habits, and manage stress. The allocation to a study group was determined by the availability within the group and participant’s ability to attend the scheduled intervention. Clinical data and patient-reported outcomes were collected. Fatigue was measured with the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); any increase in FACIT-F after six months was considered a positive response to the intervention. The Minimal Clinically Important Difference (MCID) for fatigue was at least a four-point increase in the FACIT-F score¹. Inverse probability treatment weighting was used to correct confounding by indication.

Results

Thirty-six patients in the intervention group and 32 in the control group were compared. After six months, more patients in the intervention group (82.1% of patients) than in the control group (54.2% of patients) experienced improvement in fatigue, P = 0.029. Likewise, significantly more patients in the intervention group (71.4% of patients) than the control group (33.3% of patients) achieved a MCID regarding fatigue; P = 0.006. The improvements in fatigue were sustained throughout the study period in the intervention group. Acceptance of the health status was a significant factor for improvement in fatigue (β 7.813, SE 1.908, P < 0.001). Compared to the control group, quality of life improved in the intervention group; these patients gained 0.05 more quality-adjusted life years throughout the study. Last but not least, significant improvements in dietary quality were observed as early as three months after the baseline in the intervention but not the control group; these improvements in the intervention group were sustained throughout the study period.

Conclusion

Multimodal lifestyle intervention improves fatigue, quality of life, and dietary quality in patients with IBD who are in remission. Acceptance of the health status appears essential for fatigue improvement; instruments evaluating acceptance could help to personalize treatment and maximize its effectiveness.

References

1. Cella D, Yount S, Sorensen M, et al. Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis. J Rheumatol 2005;32:811-9.

Disclosure

AEvdMdJ received unrestricted research grants from Galapagos, Norgine, Vedanta, Nestle, including speaker’s fees from Galapagos, Tramedico, Takeda, Ferring, and Janssen Pharmaceuticals. PWV has received speaker fee from Galapagos and Takeda and served on the advisory board of Lilly, Galapagos, Janssen, BMS, Takeda, and Abbvie. RL has received travel expenses from Galapagos and Cablon Medical and served on the advisory board at Cablon Medical. NW and MJHB are employed by the non-profit organization Voeding Leeft and were a part of the team that guided participants in the intervention group. All other authors have no conflicts of interest to declare.

Introduction

Vedolizumab is one of the current treatments for patients with inflammatory bowel disease (IBD). The efficacy and safety, along with its gut specificity, make this drug an appealing therapeutic option for IBD patients with moderate to severe disease. However, as observed for other biologic treatments, a significant proportion of patients do not have an initial response to vedolizumab treatment. Currently, there is a lack of reliable predictive tools for vedolizumab treatment response, although this would help to alleviate the socioeconomic costs derived from this disease.

Aims & Methods

The primary aim of this study is to show putative transcriptional signatures associated with vedolizumab treatment response.
Methods: For the realization of this study, we used RNA-seq datasets from the Gene Expression Omnibus (GEO) database: GSE191328. This dataset includes samples from peripheral blood cells from responder and non-responder ulcerative colitis (UC) patients treated with vedolizumab and infliximab at baseline. Gene Set Enrichment Analysis (GSEA) was performed to compare the differential expression and the enrichment analysis was calculated using ssGSEA of the different groups under study.

Results

The analysis of the transcriptome of peripheral blood cells from responder (R) and non-responder (NR) vedolizumab-treated patients at baseline revealed interesting enrichment results. We found 20 gene sets positively enriched in NR versus R and only 9 gene sets negatively enriched in the same phenotypes. In order to find vedolizumab specific transcriptional signatures, we performed a similar analysis in samples from infliximab-treated patients. After that second round of analysis, we observed that around 50% of the enriched gene sets were similar for both biological treatments. Nevertheless, several interesting biological functions such as peroxisome function, reactive oxygen function or beta-catenin signalling are specifically enriched in NR patients to vedolizumab treatment.

Conclusion

Our data suggest that vedolizumab NR patients specifically show a transcriptional enrichment profile, which differs from vedolizumab R patients. Also, the comparative analysis with infliximab-treated patients reveals that those specific transcripts are modulated in response to this α4β7 integrin antibodies in peripheral blood cells. Therefore, we found a solid system to search for vedolizumab therapy predictive response markers using low invasive techniques.

Introduction

Chronic fatigue (CF) is prevalent among patients with ulcerative colitis (UC) and Crohn's disease (CD), but the influence of the disease activity is not established.

Aims & Methods

The primary aim of this study was to evaluate the prevalence and probability of chronic fatigue (CF) in patients with CD and UC one year after diagnosis, stratified by different measures for disease remission (symptomatic, biochemical, endoscopic, and histological). Additionally, we aimed to evaluate factors associated with chronic fatigue among patients in endoscopic/radiological remission.

Patients ≥18 years with CD and UC were recruited from the Inflammatory Bowel Disease South-Eastern Norway (IBSEN III) study, a population-based, observational inception cohort. Fatigue was assessed using Fatigue Questionnaire (FQ), and CF was defined as a dichotomized score of ≥4 with a duration of ≥6 months. Only patients with complete FQ data, without history of colectomy, were eligible for inclusion. Binary logistic regression analyses were used to examine the probability of CF for various indicators of remission, including i) symptomatic remission (Harvey–Bradshaw index score <5 for CD and Simple Clinical Colitis Activity Index score <3 for UC), ii) biochemical remission (Fecal calprotectin ≤ 250 µg/g), iii) endoscopic/radiological remission (Mayo endoscopic score 0 in UC, and endoscopically verified absence of inflammation combined with normal intestinal MRI/CT in CD), and iv) histological remission (normal histology in all mucosal biopsies). Additionally, in patients with endoscopic/radiological remission, associations between CF and selected clinical factors were evaluated using binary logistic regression analysis.

Results

In total, 711/1416 patients with CD or UC diagnosis were included (CD: 33.8%, UC: 66.2%). Among them, 619 (87.1%) underwent colonoscopy, intestinal MRI/CT and/or fecal calprotectin testing. Prevalence of CF stratified by different indicators of remission is presented in table 1. In univariate binary logistic regression analysis regarding measures for disease remission, the probability of CF was only significantly reduced in patients with UC in symptomatic remission (OR: 0.48 (0.30, 0.77), p=0.003). Among patients with CD and UC in endoscopic/radiological remission (n=181), CF was independently associated with current biological treatment (OR: 2.92 (1.002, 8.49), p=0.05) and sleep disturbance (OR: 6.23 (2.03, 19.14), p=0.001) in multivariate logistic regression.

Table 1: Prevalence of chronic fatigue among CD and UC patients with different measures for remission one year after diagnosis
Abbreviations and table legends: CD: Crohn’s disease. UC: Ulcerative colitis. Symptomatic remission: Simple Clinical Colitis Activity Index (SCCAI) score <3 for UC / Harvey–Bradshaw index (HBI) score <5 for CD. Biochemical remission: Fecal calprotectin ≤ 250 µg/g. Endoscopic/radiological remission: Mayo endoscopic score 0 in UC and absence of intestinal disease on endoscopy and/or intestinal MRI/CT in CD. Histological remission: normal histology in all mucosal biopsies.
	CD (% (n/n total))	UC (% (n/n total))
Symptomatic remission	33.6 (51/152)	30.0 (85/283)
Biochemical remission	33.3 (25/75)	34.6 (62/179)
Endoscopic/radiological remission	40.4 (21/52)	33.3 (33/99)
Histological remission	36.8 (14/38)	35.0 (28/80)

Conclusion

The probability of CF one year after diagnosis was not associated with either low fecal calprotectin level, normal endoscopic/radiological examinations, or normal histology. Among patients with UC, but not CD, symptomatic remission was associated with a reduced probability of CF. For patients in endoscopic/radiological remission, CF was independently associated with sleep disturbances and current biological treatment.

Disclosure

All authors report no conflict of interest.

Introduction

Ustekinumab (USK) is a biological drug that inhibits interleukins 12 and 23. It has been approved for the treatment of inflammatory bowel disease (IBD) as an induction agent, which is administered intravenously, followed by a maintenance subcutaneous therapy at a dose of 90 mg every 8 or 12 weeks. In patients who do not achieve an adequate response with the usual doses, a common clinical practice is to optimise the USK dose.

Aims & Methods

The objective of this study was to evaluate the existence of risk factors associated with the need for this dose optimisation.
Methods: This was a retrospective observational single-centre study which included all adult patients with IBD treated with USK between 2013 and 2023 in the IBD Unit of the Santiago de Compostela Hospital, Spain. The following variables were evaluated: demographic variables (age, sex, BMI, smoking habit), descriptive variables of the disease (type, extension, behaviour, perianal involvement), biomarkers (calprotectin, CRP) and endoscopic characteristics. Furthermore, intestinal ultrasound was conducted in patients with Crohn's disease (CD). Dose optimization was defined as a reduction in the time interval between USK doses. The chi-square test was employed for qualitative variables, while quantitative variables were analysed using the Shapiro-Wilk test, Student's t-test, and Mann-Whitney U test. A multivariate logistic regression analysis was conducted to identify factors associated with the need for therapy optimization. Drug persistence measurements were represented using the Kaplan-Meier method.

Results

A total of 189 patients (50.3% men) with a mean age of 51.9 years (SD 16.7) were included in the study. Crohn's disease (CD) was present in 84.7% of the patients, while the remaining patients had ulcerative colitis (UC). The dosage of ustekinumab (USK) was optimised to 90 mg/4 weeks in 67.2% of all patients (69% in CD and 63% in UC). The univariate analysis revealed that BMI (p = 0.023), disease pattern (p = 0.016), presence of perianal disease (p = 0.011), high calprotectin levels (p = 0.039) and CRP (p = 0.006) were significantly associated with the need for therapy optimisation. In the logistic regression analysis, BMI was the only significant risk factor for dose intensification of USK (OR 1.093, IC 95% 1.001-1.194). Conversely, an identified protective factor was an inflammatory pattern (OR 0.234, IC 95% 0.069-0.800). The mean time from the commencement of therapy to the necessity for optimisation was 10 months in patients with CD and 5 months in patients with UC.

Conclusion

In more than half of the patients treated with ustekinumab, dose optimization is required. The necessity for dose optimization of ustekinumab in patients with Crohn's disease may be influenced by a higher body mass index value and the non-inflammatory pattern of the disease.