Introduction

Bowel Urgency (BU), identified as the sudden need for bowel movements, is increasingly being recognized as an impactful symptom in patients with Ulcerative Colitis (UC), distinct from Stool Frequency (SF) and Rectal Bleeding (RB).

Aims & Methods

We aimed to assess the association of bowel urgency (BU) with Patient-Reported Outcomes (PRO), including stool frequency (SF) and rectal bleeding (RB), along with endoscopic findings in a real-world setting. Additionally, we investigated its impact on disability and quality of life.
A cross-sectional multicenter study, which consecutively enrolled UC patients aged ≥ 18 years, was conducted between February 2023 and October 2023 using data from the 'IBD-Disk: Italian translation and validation study. Demographic, clinical and endoscopic data were collected. Clinical remission was defined as partial Mayo score ≤ 1 and endoscopic activity as MES ≥ 2. All patients completed the following questionnaire for disability IBD-Disk and IBD Questionnaire-32 (IBDQ-32) for quality of life. BU was assessed using the question about regulating defecation in the past 7 days using a 10-point NRS ranging from 0 (absolutely disagree) to 10 (totally agree) from the IBD-Disk. RB was measured from question 22 of IBDQ and SF from question 1 of IBDQ-32, both using a 7-point NRS ranging from 0 (always) to 7 (never).

Results

209 UC patients with a median age of 37 (IQR 28-52) were enrolled, 111 (53.1%) being female. Overall, 31 (14.8%) had proctitis, 91 (45.5%) had left colitis and 87 (41.6%) had extended/pancolitis. The median pMAYO score was 4 (IQR=2-6), while the median MES was 2 (IQR=1-2). 75% patients (35.9%) reporting BU were more likely to have moderate clinical (pMAYO=5; IQR=3-6) and endoscopic activity of disease (median MES=2; IQR=1-2) compared to those without urgency (p< .0001). Additionally, BU was associated with a higher median rate of hospitalizations in the previous 12 months (Δ=1; p<0.001). Patients with BU reported a higher degree of RB (33.3%) and SF (50,7%) than patients without BU (p< .0001). Noteworthy, individuals with BU had higher median IBD-Disk total score (29; IQR=9-52) and lower scores for IBDQ-32 (168; IQR=138-196) compared to patients without BU [median IBD-Disk=17 (IQR=5-39); median IBDQ-32=181, IQR=158-202), p<0.001]. In the univariate analysis, BU was associated with a higher IBD-Disk total score (OR=1.04, CI=1.02-1.06; p<0.001) and SF (OR=0.59, CI=0.45-0.78; p=0.001), without being associated with RB (p=0.57) and IBD-Q32 total score (p=0.84).

Conclusion

BU can be a surrogate marker for UC clinical and endoscopic activity. Our findings suggest that BU is an independent factor from RB and it is associated with disability. Hence, it can be considered as an additional key PRO in UC. However, a systematic standardized approach for BU definition and assessment is strongly awaited to incorporate it as treat-to-target endpoint.

References

1. Dubinsky M, Am J Gastroenterol. 2023 Nov 1;118(11):1940-1953. doi: 10.14309/ajg.0000000000002404. .
2. Caron B, Clin Gastroenterol Hepatol. 2023 Jun;21(6):1403-1413.e27. doi: 10.1016/j.cgh.2023.02.029..
3. Ghosh S, Inflamm Bowel Dis. 2017 Mar;23(3):333-340. doi: 10.1097/MIB.0000000000001033. .

Introduction

Bowel urgency is one of the most bothersome symptoms of ulcerative colitis (UC) and have a great impact on quality of life and psychosocial function. The Urgency Numerical Rating Scale (U-NRS) is desinged to ojectify this subjective symptom. It measures the degree of faecal urgency experienced over the past 24 hours by patients with UC on a scale of 0-10. We assumed that the scale has a large variance, as patients evaluate their own symptoms differently, the urge may be different quality for two patients with the same score.

Aims & Methods

The objective of our study was to investigate the possible components of urgency and refine the assessment of urgency. Patients with UC older than 18 years treated at our departments for at least 3 months and having complaints were enrolled in our study. The patients filled out our non-validated questionnaire with questions about fecal urgency (U-NRS), pain level, speed of urge, incontinence and lifestyle characteristics associated with incontinence. Statistical analysis was performed using STATA 18 program.

Results

263 patients were enrolled, median age was 39.5 years, the mean of disease duration was 11.7±9.2 years. The mean U-NRS score was 3.2±3.2, 32% (84/263) had 0 score and 3% (9/263) has 10 score. 12% of the patients (n=31) felt most difficult to hold mucus, 37% (n=97) stool and 29% (n=76) other secretions. 8% (n=22) had urge with every stool in the last 24 hours, 36% (n=95) had less than half of defecations. The speed of urge defined more the level of urgency than the pain level (R2=0.798 p<0.001, β=0.894 vs R²=0.805, p<0.001, β=0.117). The duration of faeces holding in the last 7 days had significant connection to U-NRS (R²=0.211, p<0.001, β=-0.46). Patients using public restroom at least once during the last week had significantly higher score on U-NRS than other patients (4.6±3.1 vs 2.4±3 p<0.001). 12% (31/263) used diaper. The usage of diapers was also significantly more often in patients with higher U-RNS score (5.2±3.2 vs 2.9±3.1,p<0.0001). Faecal leakage both during the day and night was significiantly higher with higher U-NRS score (p<0.001 for both). Patient reported outcome (PRO2) had a weak correlation with U-NRS (R²=0.14). However if we examine bloody stool, the stool number and difficulty of faecas holding seperately we got a significant and better correlation with urgency (R²=0.43). Patients with moderately severe-severe disease (PRO2 > 5) had a higher chance to have urgency (AUC=0.9). The possibility was higher to have urgency among patients with painful defecation (R²=0.41). The level of urgency, duration of faeces holding and the frequency of faeces holding problems had the strongest correlation with U-NRS (R²=0.83). Patients defined urgency with these parameters according to this result. We created score with them, level of urgency points + half of duration points + frequency, which showed a good model to refine the definition of urgency (R²=0.83).

Conclusion

Bowel urgency affects UC patients' lives and is associated with more severe disability. Bowel urgency is common in UC affecting about two-third of patients and associates with more severe activity of UC. Fecal urgency can characterize with the level of urgency, duration of faeces holding and the frequence of stool more accurately than a single, subjective numeric scale. A new scoring system is needed to more accurately assess patients' complaints in this area and to objectify severity.

Disclosure

The authors have no potential conflict of interest to disclose

Introduction

Real-world (RW) data on the use of Filgotinib (FILGO) in patients with ulcerative colitis (UC) are limited. We aimed to investigate its effectiveness and safety in UC patients.

Aims & Methods

A retrospective assessment of clinical and endoscopic activity was performed according to the full Mayo score. The primary endpoints were to evaluate the effectiveness and safety of FILGO.

Results

We enrolled 102 patients with a median (IQR) follow-up of 24 (8-24) weeks. At 8-week, clinical remission was achieved by 38 (37.2%) patients; at the end of follow-up, clinical remission was achieved by 47 (46.1%) patients. Clinical remission was obtained by 13/18 (72.2%) of patients in first-line therapy, by 7/19 (36.8%) of patients in second-line therapy and by 27/65 (41.5%) of patients in third-line therapy (p=0.002). At univariate analysis female sex (OR=2.65 [95% CI=1.14 to 6.17], p=0.024) and clinical remission at 8-week follow-up (OR=6.70 [95%CI=2.59 to 17.30], p=0.000) significantly predict final clinical remission, while being on second/third line treatment (OR=0.22 [95%CI=0.06 to 0.74], p=0.014), was a negative factor for clinical remission. At multivariate analysis, clinical remission at 8-week follow-up (OR=2.21 [95%CI=1.13 to 4.34], p=0.021) was the only factor predicting clinical remission, while both age >40 years (OR=0.46 [95% CI=0.22 to 0.99], p=0.046) and being on second/third line treatment (OR=0.31 [95%CI=0.14 to 0.69], p=0.005) were negative predictive factors for clinical remission. Clinical response was achieved by 71 (69.6%) patients. At endoscopic assessment, mucosal healing was observed in 18/30 (60.0%) patients. Steroid-free remission was present in 38/46 (82.6%) patients. Surgery was necessary in 5 (4.9%) patients.

Conclusion

Our RW data confirm that FILGO is effective and safe in UC patients. It performs remarkably better when used as the first line of treatment.

Introduction

Ustekinumab (UST) is a monoclonal antibody against the p40 subunit, common to IL-12 and IL-23 and was approved recently for the treatment of moderate to severe ulcerative colitis (UC).

Aims & Methods

The aim of this ongoing study is to report and analyze data from a large cohort of Greek patients with UC, who receive treatment with UST. We collected data from patients with UC from 14 Greek hospitals who commenced treatment with UST and evaluated their clinical response at week 16. Clinical response was defined as 50% reduction in the UC PRO2 values at week 16 compared to the values before treatment (baseline).

Results

Herein, we report the clinical outcomes at week 16, following the completion of induction regimen (i.v. loading 6mg/kg plus 1^st 90mg sc injection at week 8). The demographics and disease characteristics of the first 101 enrolled patients are shown in Table 1. The majority of patients (70, 70%) commenced treatment with UST due to active disease despite previous treatments. Seventy-six patients (76%) had been exposed to at least one biologic agent, most commonly anti-TNFs (54%). Thirty-eight (38%) and 29 (29%) patients were exposed to one and two biologics, respectively. Sixteen patients (16%) had previously received both infliximab (IFX) and vedolizumab (VDZ). Corticosteroids (50%) and mesalazine (5-ASA, 68%) were the most common concomitant treatments. UST was discontinued in 4 patients due to no response. A total of 79 patients have reached the 16^th week time-point, out of whom 61 have enough data to be analyzed. Analysis of the patients who had active disease at induction (total number with adequate data: 50) showed that clinical response was achieved in 36 (72%) and clinical steroid-free remission in 23 (46%) patients. In multiple logistic analysis concomitant use of 5-ASA was associated with a higher probability of clinical response at week 16 (P=0.009), while hemoglobin >13.1g/dL (P=0.047), and age >60 years (P=0.059) were associated with a lower probability of response. Seven patients were receiving concomitant corticosteroids at week 16.

Conclusion

In a real world clinical setting, UST was mostly used as a 2^nd or 3^rd line treatment for moderate to severe UC. At the end of induction treatment, the majority of patients showed clinical response and almost half were in steroid-free remission. Positive predictive factors of response to UST included the concomitant use of 5-ASA, while Hb >13.1 g/dl and age >60 years were associated with lack of response.
Funding: This study was funded through a research grant from the Greek IBD study group (EOMIFNE) to G.B. EOMIFNE grant: 2022EOMIFNEmp1

Disclosure

GB: Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma,
Adacyte Therapeutics, Amgen, Ferring, Cooper; Funding (Grants/Honoraria): Pfizer, Takeda,
Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda.
EZ: Advisor/lecturer for Pfizer, Takeda, Abbvie, Amgen, Genesis Pharma, Aenorasis, Janssen
SM: Advisory/Lecturer for Pfizer, Takeda, Abbvie, Ferring, MSD, Janssen
GM: Advisor/lecturer for AbbVie, Celgene, Celtrion, Ferrirng, Genesis, Hospira, Janssen,
Millennium Pharmaceuticals, MSD, Mylan, Pharmacosmos, Pfizer, Takeda, VIANEX, Angelini,
Falk Pharma, Galenica, Omega Pharma; Consultancies for MSD and Takeda; Research support
from AbbVie, Galenica, Genesis, Menarini Group, MSD, Pharmathen.
KK: Advisor/lecturer for Abbvie, Aenorasis, Janssen, MSD, Pfizer and Takeda, Amgen, Ferring,
Galenica, Genesis Pharma.
MT: Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma,
Amgen, Research/Clinical Trials: AbbVie, Gilead, Takeda

Introduction

Upadacitinib (UPA) is an oral selective small molecule JAK inhibitor emerged as a promising therapeutic agent for immune-mediated inflammatory diseases. Recently, UPA has been evaluated for the treatment of moderate-to-severe ulcerative colitis (UC) with encouraging phase III trials. The aim of this real-life observational study is to explore the effectiveness and safety of UPA in UC patients in a large multicenter italian cohort.

Aims & Methods

UPAREAL-UC is an observational multicenter study involving 36 IBD centers in Italy. UC patients who have been prescribed UPA between 01.2023 and 11.2024 were enrolled and prospectively followed-up. Main outcomes were steroid-free clinical remission, biochemical remission and treatment persistence. Five main evaluation time-points were defined: T0 (baseline), T1 (8weeks), T2 (16weeks), T3 (26weeks) and T4 (52weeks). At each time-point, partial Mayo score (pMS), fecal calprotectin (FC) and C-reactive protein (CRP) levels were recorded. Steroid-free clinical remission was defined as pMS<2, FC remission as FC <250 ug/gr, CRP remission as CRP<0,5 mg/dl. Treatment-related adverse events were also reported. To investigate the correlation between the variables Fisher exact test was used.

Results

Among 367 UPA patients included in the multicenter on-going study, we present the results of the first 250 patients with at least 12 months of follow up (enrolled until 03.2024). At baseline all patients were bio-exposed, the majority of them presented with moderate-severe UC and the median age was 40 years. Extraintestinal manifestations were observed in 10 % of patients and cardiovascular risk factors in about 15%.
Steroid-free clinical remission was achieved in 175 (70%), 197 (78,8%), 195 (78%) and 175 (70%) patients at T1, T2, T3 and T4, respectively. CRP and FC showed a significative reduction with a biochemical remission at T3 and T4 in about 70% of patients for both CRP and FC. The composite endpoint, defined as the presence of steroid-free clinical remission and biochemical remission (both CRP and FC), was achieved in 135 patients (54%) at T3 and in 145 patients (58%) at T4. All these improvements were statistically significant (p<0,0001). Treatment persistence at 12 months was 82 %. The need for a prolonged induction occurred in 54% patients. Adverse events occurred in 12,8 % patients, treatment failure occurred in 16% with a median time to failure of 18 weeks.

Conclusion

These preliminary data coming from large on-going multicentric IG-IBD study conducted in a real-life setting, confirm promising effects of UPA in inducing steroid-free clinical remission and in normalizing markers of inflammation. A significant 12-months treatment persistence was observed. No serious adverse events occurred. Long-term prospective data, including endoscopic and histologic evaluations, are needed and will be available at the end of this ongoing study.

Introduction

Disability is a multidimensional concept encompassing physical, psychological, and social limitations that can significantly burden individuals living with inflammatory bowel disease (IBD). However, as disability is shaped by various factors—including cultural, social, and healthcare-related influences that can differ between countries—its prevalence and characteristics may vary globally.

Aims & Methods

We aimed to meta-analyse global data on prevalence of moderate-to-severe disability (MSD) to explore differences in disability prevalence and characteristics by country, IBD subtype, disease activity. MEDLINE EMBASE, EMBASE Classic (from inception to 1^st December 2024) to identify cross-sectional and case-control studies reporting the prevalence of MSD based on validated tools (IBD–Disk and IBD-Disability Index) in adult patients (≥18 years) with confirmed IBD. Data were extracted, and pooled prevalence (PP), odds ratios (OR), and 95% confidence intervals (CIs) were calculated.

Results

The search strategy generated 3089 citations. From these, 160 individual articles appeared to be relevant to the study question and 17 fulfilled the eligibility criteria, containing 8225 patients with IBD recruited from 11 different countries. The pooled prevalence of MSD in patients with IBD was 29.6% (95% CI 22.6-37.1%; I²=98.0%, p<0.01), with no evidence of funnel plot asymmetry (Egger test, p=0.10). The lowest pooled prevalence of MSD was 7.0% in one Dutch study from the Netherlands, and the highest 51% and 52% in two studies from China and Italy, respectively. The pooled prevalence of MSD was higher in patients with IBD with active disease (56.9%, 95% CI 20.3-89.7%, I² = 93.0%, p<0.01) compared with those with inactive disease (27.0%, 95% CI 3.3-62.0%, I² = 93.0%, p<0.01). Based on three studies that reported MSD prevalence in both active and inactive disease, active IBD increased the odds of MSD more than threefold (odds ratio 3.13, 95% CI 1.74-5.64).

Conclusion

The global prevalence of MSD in the IBD population is 29.6%, and even higher among patients with active disease. These findings underscore the value of incorporating disability assessment into both clinical decision-making and routine therapeutic response —especially in the context of disease modification trials.