Introduction

Psychological symptoms are associated with negative ulcerative colitis (UC)-related outcomes, such as increased symptom severity and decreased health-related quality of life (HRQOL). However, the majority of research to date is cross-sectional, limiting our ability to assess the impact of psychological processes on longitudinal IBD-related outcomes and the directionality of such effects.

Aims & Methods

We aimed to identify patient subgroups based on the longitudinal evolution of GI symptom levels and HRQOL and disentangle the directionality of effects between GI symptom levels and levels of psychological distress. Self-reported symptom severity,¹ HRQOL,² inflammatory biomarkers, psychological distress,³ and coping⁴ were assessed in 98 newly diagnosed UC patients (mean age = 36 [range 18–74], 69% male) at baseline (before anti-inflammatory treatment) and yearly for 3 consecutive years. Latent-class growth analysis (LCGA) was used to determine subgroups in longitudinal trajectories of symptom severity (diarrhea, abdominal pain) and physical and mental HRQOL. Risk factor analysis was used to determine psychological and inflammatory baseline predictors of trajectory group membership. Cross-lagged structural equation models were used to disentangle psychological predictor – symptom severity temporal relationships.

Results

Different subgroups were found based on the progression of diarrhea, abdominal pain, and physical and mental HRQOL over time. Patients with more psychological symptoms at baseline had an increased probability of maintaining higher levels of diarrhea (p = 0.049) and abdominal pain (p = 0.009) over time. Conversely, patients with lower levels of baseline diarrhea (p < 0.001) and abdominal pain (p = 0.003) had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment (p = 0.017), suggesting a subgroup of patients for whom initial poor mental health was inflammation-driven. Cross-lagged structural equation models indicated that reductions in abdominal pain preceded reductions in psychological symptoms in time (all β=0.75, p <.001). Both diarrhea and abdominal pain preceded reductions in coping resources in time (diarrhea: β_baseline= -0.16, β₁= -0.10, β₂= -0.12, all p <.05; abdominal pain: β_baseline= -0.31, β₁= -0.18, β₂= -0.21, all p <.001).

Conclusion

Baseline psychological distress is predictive of higher maintained levels of symptom severity over time, suggesting early assessment of psychological symptoms may identify patients with worse disease trajectories. IBD symptom and disease severity also contribute to mental health outcomes; indeed, low baseline symptom severity may be protective against subsequent decreased mental health and reducing inflammation may improve mental health functioning in a subset of patients. When evaluating the directionality of psychological predictor–symptom severity relationships over time, abdominal pain predicted increased psychological distress, but not the other way around. Thus, interventions aimed at reducing abdominal pain may help prevent or reduce future psychological distress.

References

1. Svedlund, J., Sjödin, I., & Dotevall, G. (1988). GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Digestive diseases and sciences, 33(2), 129–134. https://doi.org/10.1007/BF01535722.
2. Bernklev, T., Jahnsen, J., Lygren, I., Henriksen, M., Vatn, M., & Moum, B. (2005). Health-related quality of life in patients with inflammatory bowel disease measured with the short form-36: psychometric assessments and a comparison with general population norms. Inflammatory bowel diseases, 11(10), 909–918. https://doi.org/10.1097/01.mib.0000179467.01748.99.
3. Zigmond, A. S., & Snaith, R. P. (1983). The hospital anxiety and depression scale. Acta psychiatrica Scandinavica, 67(6), 361–370. https://doi.org/10.1111/j.1600-0447.1983.tb09716.x
4. Matheny, K. B., Aycock, D. W., Curlette, W. L., & Junker, G. N. (1993). The coping resources inventory for stress: a measure of perceived resourcefulness. Journal of clinical psychology, 49(6), 815–830.

Disclosure

Test

Introduction

Early identification of factors that predict disease course in ulcerative colitis (UC) is essential to guide therapeutic decisions and improve patient outcomes. Recognizing patients at higher risk of unfavorable evolution allows for more intensive monitoring and timely escalation of therapy. Clinical severity, disease extent, histological activity, and concomitant infections may all influence prognosis. Among these, Clostridioides difficile infection (CDI) is increasingly recognized in UC patients, but its independent impact on disease evolution remains uncertain. The objective of our study was to assess various baseline severity markers, including histological activity, and concomitant CDI at the time of UC diagnosis as potential predictors of disease-related morbidity during the first year following UC diagnosis.

Aims & Methods

We conducted a retrospective study on a cohort of 125 patients newly diagnosed with UC and followed for at least 12 months. Data collected included demographic characteristics, clinical presentation, biochemical markers, endoscopic findings, histologic disease activity (assessed using the Nancy Histological Index – NHI), and the presence of CDI at diagnosis. Disease-related morbidity was defined as any UC-related hospitalization occurring in the first year after diagnosis, excluding the initial admission for diagnostic purposes. Statistical analysis involved bivariate comparisons and multivariate logistic regression to identify independent predictors of hospitalization.

Results

Independent predictors of UC-related hospitalization were Mayo clinical score (OR = 1.32; p = 0.016), pancolitis (OR = 2.82; p = 0.024), and histological activity (NHI; OR = 1.97; p = 0.014). CDI was identified in 20% of patients and was associated with significantly higher histological activity (median NHI = 3.5 vs. 3.0; p = 0.036), but did not independently predict hospitalization (OR = 1.84; p = 0.265).

Conclusion

Clinical activity, disease extent, and histological severity, at the time of diagnosis are strong, independent predictors of UC-related morbidity within the first year, underscoring their prognostic value beyond the initial presentation. These parameters retain their significance over the medium-term disease course, supporting early risk stratification and individualized treatment planning. Although CDI is associated with greater histologic inflammation at baseline, it does not independently influence outcomes during the first year. Notably, the identification of UC in 20% of patients during a CDI episode suggests that acute infection may unmask previously subclinical disease. These findings highlight the need for comprehensive and careful diagnostic evaluation - including clinical, endoscopic, and histologic assessment, in all patients with newly diagnosed UC.

Introduction

Psychological distress and gut dysbiosis are key factors in patients with IBD.

Aims & Methods

This study aimed to assess whether specific psychopathological and gut microbiota features could predict adverse outcomes in patients with UC. In this follow-up study, we enrolled 35 adult patients with UC. At baseline, patients completed a psychometric evaluation and provided a stool sample for gut microbiota analysis. For the purposes of this study, only trait-focused scales (MMPI-2, TAS-20, CD-RISC, STAI-Y2) were considered, while state-focused assessments were excluded. Five years later we reconstructed each patient’s clinical history, focusing on adverse outcomes, including failure of biological therapy, UC-related hospitalizations, and UC-related surgeries.

Results

Patients with failure of biological therapy exhibited increased levels of Proteobacteria (p = 0.006), Fusobacteria (p = 0.042), Enterobacteriaceae (p = 0.025), and Trabulsiella (p = 0.011), while Firmicutes were found to be less abundant (p = 0.036). UC-related hospitalized patients presented lower levels of Euryarchaeota (p = 0.036), Rikenellaceae (p = 0.011), Ruminococcaceae (p = 0.004), Faecalibacterium (p = 0.004), Lachnospira (p = 0.005), Methanobrevibacter (p = 0.036), Parabacteroides (p = 0.027), and Phascolarctobacterium (p = 0.011), compared to non-hospitalized patients. In contrast, they exhibited higher levels of Collinsella (p = 0.029). Considering the psychometric scales, UC-related hospitalized patients had higher scores on the Sc clinical scale (p = 0.032) and higher scores on the OBS (p = 0.044) and HEA (p = 0.026) content scales. Acidaminococcus (p = 0.023) and Bilophila (p = 0.045) were significantly more abundant in patients that underwent UC-related surgery compared to patients who do not. Patients with complications related to inflammation spread showed at baseline lower abundance of Coprococcus (p = 0.004) compared to other patients. Regarding the psychometric scales, patients with this feature had lower scores on the STAI-Y2 (p = 0.007), higher scores on the Mf clinical scale (p = 0.029), and lower scores on the Sc clinical scale (p = 0.044) and the BIZ content scale (p = 0.022). A PCA analysis, specifically conducted on the phyla, revealed differences only between patients who experienced at least one biological failure and those without therapy failure (PERMANOVA: F = 24.2, p = 0.049, explained variance = 48.89%). Other PCA analyses did not show significant differences between the various groups.
At the binary logistic regression, Fusobacteria was negatively correlated with the failure of three or more biologics (OR = 0.000; B = -10,584.860, p = 0.028). Hy and Pd were positively correlated with the failure of three or more biologics (OR = 2.167; B = 0.773, p = 0.044) and 2.639 (B = 0.971, p = 0.024). Conversely, Pa and Pt were negatively correlated with the failure of three or more biologics, associated with odds ratios of (OR = 0.622, B = -0.476, p = 0.041 and OR = 0.152, B = -1.886, p = 0.021 respectively).

Conclusion

Psychopathological features, related to obsessiveness, health concerns, and somatization, along with specific microbiota characteristics (a lower abundance of SCFA-producing bacteria), may act as predictive factors for UC-related adverse outcomes.
​

Introduction

Patients with ulcerative colitis (UC) and their treating physicians are currently looking beyond symptom resolution to achieve mucosal healing for a better long-term outcome. The assessment of this target requires invasive tests at several occasions that has an impact on the quality of life.

Aims & Methods

To evaluate the role of serum, fecal and urine biomarkers for predicting endoscopic healing, histological improvement and long-term outcomes after medical treatment of UC.

Patients with newly diagnosed acute UC or relapse of UC between September 2018 and February 2020 were included and followed for three years for relapse of symptoms. Disease activity was measured using clinical, Mayo Endoscopic Subscore (MES), and histological scores (Geboes score and Robarts Histological index). Biomarkers such as ESR, CRP, Fecal Calprotectin, Serum NGAL and 24-hour urine potassium were done at baseline and at clinical remission. The utility of biomarkers to predict endoscopic healing (MES ≤ 1), histological improvement (Geboes ≤ 3), and disease flare on follow up were analysed.

Results

40 patients (43 episodes of UC) with a mean age of 35 ± 10 years were studied. Majority of patients had moderate to severe disease activity by clinical score (88%), MES (93%) and histology (82%). There was a significant reduction in baseline serum and fecal biomarkers and a significant increase in 24-hour urine potassium at clinical remission and those with endoscopic healing while those with histological improvement had significant reduction in fecal and serum markers only. Patients without endoscopic healing or histological improvement didn’t had significant changes in biomarkers.

Parameter	Achieved endoscopic healing(n=36)			Achieved histological improvement(n=18)
	Baseline	Clinical remission	P value	Baseline	Clinical remission	P value
Fecal calprotectin(µg/g)	612.57 (31.- 8249.2)	147.36 (10 – 4463)	0.01*	921.3(79.4 – 8249.2)	66.26(10.01 – 1345.2)	<0.001*
Serum NGAL(ng/ml)	35.4 (22.8 – 1077.8)	31.75 (19 – 682.6)	0.003*	36.04(25.6 – 1077.8)	28.49(19.08 – 682.6)	0.002*
24-Hour urine potassium(meq/day)	27(6.6 -200)	36.8(10-240)	0.002*	24.77 ± 12.05	47.47 ± 52.7	0.07#
	Endoscopic healing(n)			Histological improvement(n)
	Yes	No	P value	Yes	No	P value
Flare	14	4	0.25$	4	14	0.02$
No flare	13	1		9	5
*: Wilcoxon sign rank test, #: paired t test, $ : chisquare test

Among patients achieving clinical remission, 83.7% (n= 36) had endoscopic healing and 41.8% (n=18) had histological improvement. 14 patients (35 %) had worsening of fecal calprotectin despite a clinical remission. A reduction in the baseline fecal calprotectin levels by 33.89% (AUC: 0.802, sensitivity: 0.72, specificity: 0.86) and 67.8% (AUC: 0.869, sensitivity: 0.83, specificity: 0.68) predicted endoscopic healing and histological improvement respectively.

A total of 32 patients completed the three year follow up and 54.5% (n=18) had at least one disease flare. Fewer patients with histological improvement (n=4; 12.5%) after treatment experienced flares compared to those with endoscopic healing (n=14; 77.7%). Although two-third with worsening fecal calprotectin achieved endoscopic healing on follow up, none had histological improvement and everyone had symptom relapse on follow up.

Conclusion

Our study confirmed that one-third to two-third decline in fecal calprotectin with treatment predicted endoscopic healing and histological improvement in UC. As the disease flares during follow up was better predicted by an improvement in histology, a two-third fall in baseline calprotectin may be a useful marker for better long-term outcomes in UC.

Disclosure

None declared

Introduction

Proper and timely risk stratification of inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is essential to tailor personalized treatment.

Aims & Methods

The aims of the current study were to report the early disease course of newly diagnosed UC and CD and identify risk factors for a severe disease course. Patients were identified from an ongoing prospective population-based inception cohort at Hvidovre University Hospital and Herlev University Hospital, IBD Prognosis Study, which includes all patients with newly diagnosed IBD since May 2021 and forth within a catchment population of 1.050.000 (~20% of the Danish population). We defined severe disease course as the need for surgery or initiation of biological therapies within six months of diagnosis. A Cox proportional hazard model with Bonferroni correction adjusting for multiple comparisons was constructed to identify predictors hereof.

Results

As of April 15^th, 2023, the cohort comprised 501 patients, including 287 with UC,180 with CD, and 34 with IBD unclassified (IBDU). The mean age (interquartile range (IQR)) at diagnosis was 39 years (27-56), 36 (25-54), and 36 (27-52), respectively. The cumulative risk of a severe disease course within six months after the onset of UC, CD and IBDU was 3.8% (95% confidence interval 1.9-6.8), 13.9% (95% CI 9.2-19.8) and 11.4% (95%CI 3.2-26.7).
In a Cox multivariable regression model adjusting for age and gender, a severe initial disease course for UC was predicted by extensive disease distribution, severe disease endoscopically at diagnosis, and affected biochemical inflammation parameters (Table 1). In patients with CD, perianal disease but no other phenotypic characteristics were predictive for the initial course. However, in a sensitivity analysis of luminal CD, stricturing phenotype at diagnosis (adjusted hazard ratio (aHR) = 4.6 (95% confidence interval (CI) 1.5-13.6), the platelet count (HR= 1.3 (95% CI 1.2-10.6), and CRP > 10 mg/L (aHR= 14.2 (95% CI 1.9-108.5) were independently associated with a severe initial course, while initial use of systemic steroids was associated with a reduced risk. In patients with IBDU, only low hemoglobin was predictive for an initial severe disease course.

Table 1: Predictors of early severe disease course in newly diagnosed IBD in multivariate Cox proportional hazard model with Bonferroni correction (hazard ratio (95% confidence interval))

Variable	Ulcerative colitis	Crohn’s disease	IBD unclassified
Gender (Female)	0.22 (0.04-1.1)	1.3 (0.4-4.1)	2.5 (0.4-17.9)
Elderly-onset (≥60 y)	1.9 (0.5-7.3)	4.1 (0.3-12.3)	NA
Smoking (current or previous vs. never)	0.6 (0.1-2.5)	1.0 (0.34-2.9)	NA
Body mass index >30	0.6 (0.07-5.6)	3.6 (0.16-14.2)	NA
Diagnostic delay (>12 months vs. less)	1.5 (0.1-15.2)	1.4 (0.1-17.1)	NA
Treatment with systemic steroids at diagnosis	1.4 (0.1-16.4)	0.3 (0.1-0.8)	NA
Disease extent (E3) Disease location (L3) Disease behavior (B2/B3) Perianal disease	4.3 (1.6-12.5)	1.6 (0.4-8.1) 1.6 (0.4-8.1) 3.1 (0.7-15.2) 4.9 (1.6-14.9)	0.3 (0.04-2.2)
Mayo Endoscopic Score, SES-CD>16 SCCAI≥10, HBI≥8	6.0 (1.5-23.8) 1.7 (0.4-7.2)	NA 1.3 (0.8-7.7)	9.8 (0.6-15.9) 3.6 (0.3-44.2)
Hemoglobin < 7.3 mmol/L Platelet count > 450 109/L Albumin < 36 g/L C-reactive protein > 10 mg/L Fecal calprotectin > 1800	4.1 (1.2-14.1) 7.3 (1.3-41.9) 13.5 (2.8-64.2) 13.1 (1.8-20.3) 1.3 (0.3-5.9)	1.1 (0.29-4.1) 1.3 (0.3-6.5) 0.94 (0.3-2.9) 3.2 (0.8-11.7) 3.2 (0.11-2.44)	12.7 (1.2-145.6) NA 13.7 (0.3-37.5) 8.6 (0.8-16.6) 3.7 (0.4-31.8)

Conclusion

In this population-based study, we found 4%, 14%, and 11% of patients with newly diagnosed UC, CD, and IBDU, respectively, to experience an early severe disease course. Furthermore, systemic inflammation was predictive for a severe initial course in UC. In CD, perianal disease or stricturing disease phenotypes identify the subgroup of patients at high risk of early severe disease course.

Disclosure

Mohamed Attauabi: None
Gorm Roager Madsen: None
Flemming Bendtsen: Tillotts, Ferring
Klaus Theede: Ferring, Janssen, Takeda, Pfizer, and Tillotts
Jakob Benedict Seidelin: has received research grants from Takeda and Janssen and is national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly, and Boehringer Ingelheim. None of these pertain to the research submitted here.
Johan Burisch: reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants, and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work.