Ulcerative Colitis Activity Research Articles

P291 Long term outcomes of children with ulcerative colitis after acute severe colitis: a multicenter study from the GETAID pédiatrique group

Abstract Background Acute Severe Colitis (ASC) is a frequent and severe complication of ulcerative colitis (UC) that can occur at any time during the disease. Its prognosis can be severe with a high risk of colectomy. The use of immunosuppressants and more recently biotherapies seem to reduce the risk of colectomy. We wished to study the long-term evolution of paediatric-onset UC patients after ASC. Methods This retrospective study was conducted in 12 centres of the GETAID paediatric in France. Data on patients with UC aged < 18 years admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥ 65) between January 2010 and January 2021 were collected at discharge and at 1, 3 and 5 years after admission. The primary outcome of our study was colectomy-free rates at one year. A univariate analysis comparing the profile at diagnosis and at ASC of patients who underwent colectomy, and others was performed to look for prognostic factors associated with the risk of surgery. Results Of the 102 patients admitted with ASC, 95 [93%] were treated with corticosteroids. Forty-six [48%] patients were escalated to second-line therapy, mainly to infliximab. Nine patients [8.8%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 83%, 76% and 72% at 1, 3 and 5 years after initial ASC admission, respectively. In a multivariate analysis, active disease, and use of methotrexate were significantly associated with a higher risk of colectomy. A short delay between diagnosis and ASC, rapid steroid use for ASC and second line therapy with azathioprine and Infliximab were significantly associated with a lower risk of colectomy. Conclusion The rate of colostomy remains high after an episode of acute colitis despite the earlier use of biotherapies. But long-term outcome of paediatric-onset UC patients is good with sustained clinical and biological remission.

P150 Identification of features associated with poor outcomes in pediatric patients with ulcerative proctitis: A Multicentre Study From the Paediatric IBD Porto Group of ESPGHAN

Abstract Background Ulcerative proctitis (UP) is an uncommon presentation in paediatric patients with ulcerative colitis, accounting for <10% of cases. Here we aimed to characterize the clinical features and natural history of paediatric patients with UP, and to identify predictors of poor outcomes. Methods A retrospective cohort study involving 37 sites affiliated with the IBD Interest group of ESPGHAN. Data were collected at different timepoints from patients diagnosed with UP aged <18 years between 01/01/2016-31/12/2020. Outcomes included time to initiation of systemic steroids, thiopurines or biologics, time to acute severe colitis (ASC), IBD-related admission and colectomy. Univariate cox regression was used to study the association between potential predictors and study outcomes. Results Two hundred and fifty patients with UP were included, with a median age at diagnosis of 14.5 (IQR 12.3-15.9) years, and a median follow-up of 2.7 (IQR 1.7-3.9) years. The most common presenting symptoms were bloody stools (94%), abdominal pain (59%) and diarrhea (53%). At diagnosis, the median pediatric ulcerative colitis activity index (PUCAI) score was 25 (IQR 20-35), and only 3 patients (1.3%) presented with ASC. Most children had normal inflammatory markers and albumin levels. the median fecal calprotectin level was 720 mcg/g (IQR 310-1800), while 16 patients (9.9%) had a calprotectin level <100mcg/g at diagnosis. Administration of oral or topical 5-ASA resulted in clinical remission rates of 52% and 48%, respectively, by the end of induction, while the combination of both led to remission in 73% of patients. The rates of treatment escalation to thiopurines and biologics at 1, 3 and 5 years were 11%, 27% and 45%, and 11%, 23% and 45%, respectively (Figure 1). Within 5 years from diagnosis, 20% of patients had presented with ASC. The PUCAI score at diagnosis of UP was highly associated with initiation of systemic steroids, thiopurines or biologics, as well as later ASC event and IBD admission, while a Mayo endoscopic score of 3 was associated with the initiation of biologics and subsequent ASC event and IBD admission (Table 1). Seven patients (4%) underwent colectomy by the end of follow-up. Among the 151/250 patients who had a repeat endoscopy, only 16% achieved mucosal healing and in 48% inflammation extended proximally. Cecal patch (P=0.009) and higher PUCAI score (P=0.009) at diagnosis, as well as higher PUCAI score (P=0.009) and lack of steroid-free clinical remission (P=0.005) by the end of induction were associated with proximal disease extension. Conclusion Disease burden is significant in paediatric patients that present with UP, with high rates of proximal disease extension and requirement for treatment escalation.

P178 Evaluation of the Ulcerative Colitis Intestinal Ultrasound (UC-IUS) Index in Pediatric patients with newly diagnosed ulcerative colitis

Abstract Background Transabdominal bowel ultrasound (TABUS) is a non-invasive tool that can be used to assess bowel inflammation in ulcerative colitis (UC). It is particularly attractive for use in children, given the need for general anesthesia when undergoing endoscopic assessment of bowel inflammation. A standardized TABUS scoring system in UC has only been developed in adults (the UC Intestinal Ultrasound (UC-IUS) Index). Our aim was to evaluate the UC-IUS Index in Pediatric patients. Methods Pediatric patients (<18 years old) with suspected UC were prospectively enrolled. TABUS was performed for the right side colon, transverse, descending, and sigmoid colons. UC-IUS Index scores were calculated: bowel wall thickness (BWT) (>2mm=1, >3mm=2, >4mm=3), Doppler signal (spots=1, stretches=2), haustrations (abnormal=1), and fat wrapping (present=1). Mayo endoscopic subscore (for each segment), Pediatric Ulcerative Colitis Activity Index (PUCAI), and inflammatory biomarkers were collected. Non-parametric tests were used to correlate UC-IUS and BWT with Mayo endoscopic subscores. Receiver operating characteristic (ROC) analyses evaluated the UC-IUS Index BWT cut-offs. Results Fifty-two patients (56% male) were included (Table 1). Data for 206 colonic segments were analyzed (2 segments missing due to 1 incomplete colonoscopy). Total UC-IUS scores significantly correlated with CRP (rho=0.61), albumin (rho=-0.49), PUCAI (rho=0.54), FCP (rho=0.41). UC-IUS Index scores and mean BWT for each segment showed significant moderate correlations with Mayo sub-scores of that segment (rho=0.60 and rho=0.58, respectively) (p<0.001) (Fig 1). These correlations were strong in the right colon (rho=0.77, rho=0.69), and moderate in the transverse (rho=0.52, rho=0.56), descending (rho=0.43, rho=0.50), and sigmoid (rho=0.50, rho=0.46) colons (p<0.01). The adult UC-IUS 2mm cut-off (Mayo 0 vs. Mayo 1-3) performed similarly in our Pediatric patients (sensitivity 80%, specificity 96%, area under the curve (AUC) 0.92). The 3mm (Mayo 0-1 vs. Mayo 2-3) and 4mm (Mayo 0-2 vs. Mayo 3) cut-offs had lower sensitivity (sensitivity 44%, specificity 98%, AUC 0.87; sensitivity 59%, specificity 92%, AUC 0.80) (Fig 2). Thinner BWT cut-offs performed better: 2.5mm (sensitivity 65%; specificity 89%) and 3.5mm (sensitivity 71%; specificity 86%). Fig 1: Fig 2: Conclusion In Pediatric patients with newly diagnosed UC, TABUS was a useful tool, with the UC-IUS and BWT correlating well with their endoscopic, clinical, and biochemical disease activity. Compared to the adult UC-IUS Index, Pediatric patients need a thinner BWT cut-off to better discriminate between mild vs. moderate/severe disease (2.5mm instead of 3mm) and mild/moderate vs. severe disease (3.5mm instead of 4mm).

P735 Real-life experience with the use of Tofacitinib in Colombian patients with moderate to severe Ulcerative Colitis: a descriptive study

Abstract Background In Latin America the experience in clinical practice with tofacitinib for moderate to severe Ulcerative Colitis (UC), in terms of both effectiveness and safety, is still limited. In Colombia, the incidence of UC as well as the availability of these new therapeutic options has been increasing, also, patients are frequently more refractory to treatments with higher rates of hospitalizations and surgeries. The aim of this study is to describe the real-life experience in Colombian patients with UC treated with Tofacitinib. Methods descriptive observational study, patients with moderate-severe UC as defined by the American College of Gastroenterology Ulcerative Colitis Activity Index (ACG score) treated with tofacitinib in induction phase (10mg every 12 hours) and maintenance (5mg every 12 hours), in different reference centers nationwide. Therapeutic response was evaluated in endoscopic (Mayo score), paraclinical (CRP, ESR, fecal calprotectin, hemoglobin) and clinical (absence of abdominal pain, diarrhea and rectorrhagia) terms. Additionally, the frequency of adverse events, steroid use and extraintestinal manifestations were measured. Results 51 patients, 55% women, the average age was 37,14 years (range14-72). All patients had moderate to severe UC; 73% patients with pancolitis, and 21,6% with left colitis. The mean age at UC diagnosis was 29,77 (SD17,8) years (range 12.77-66,4). And the mean time between disease onset and tofacitininb initiation was 7,33 (SD17,1) years (range 0.001-22.72). 42/51(82,4%) patients had previously failed tumor necrosis factor inhibitors and 15/51(29,4%) had failed alpha4 beta7 integrin inhibitor (Vedolizumab). Six patients were naïve to any biologic drug. Ten patients had extraintestinal manifestations. During the induction phase, 68,6% achieved clinical remission, 58,8% endoscopic remission, and 60,8% paraclinical remission. During maintenance phases, information was obtained from 18 patients during the first 6 months, 16 of whom reported clinical, paraclinical and endoscopic remission, while information was obtained from 7 patients at 12 months, 5 of whom showed clinical remission, and 6/7 endoscopic and paraclinical remission. Four patients reported adverse events No thromboembolic or cardiovascular events were reported. Conclusion Tofacitinib is an effective and safe therapeutic alternative in the management of moderate-severe UC in our population. It is safe in patients with previous use of anti-TNF and anti-integrin, without presenting thrombotic or cardiovascular events. Also, it is a promising alternative in the bio-naïve patient. Its use in pediatric patients is off-label, the patients included presented clinical and paraclinical remission.

P290 Development of an artificial intelligence model using stool pictures for predicting endoscopic mucosal inflammation in patients with Ulcerative Colitis; KASID multicenter study

Abstract Background Disease monitoring through objective measures including fecal calprotectin and endoscopy is crucial for the management of ulcerative colitis (UC). The role of stool pictures taken by smart phones in the disease monitoring of UC is not known. We aimed to develop artificial intelligence (AI) model using stool pictures for predicting endoscopic mucosal inflammation in patients with UC. Methods This was a prospective multicenter study conducted in 6 tertiary referral hospitals. Patients scheduled to undergo endoscopy for monitoring of mucosal inflammation were included in the study. They were asked to send their stool photos taken at the toilet using smartphones within ± 5 days from the day of endoscopy. Endoscopic activity was assessed with Ulcerative Colitis Endoscopic Index of Severity (UCEIS). 80% and 20% of total data were randomly selected as training and validation set, respectively and this process repeated 4 times on different iterations for cross-validation. Accuracy of AI model for predicting endoscopic healing was compared with that of fecal calprotectin (Fcal). Results A total of 2463 stool pictures from 293 patients with UC were collected (mean age, year, 44±15.2; female, 108 (36.9%)). Endoscopic healing was found in 165 patients (56.3%). In validation set, the mean area under the receiver operating characteristic (AUROC) for predicting endoscopic activity using AI model was 0.78±0.02 (p=0.001) which was not statistically different from the AUROC of Fcal (0.81±0.08, p=0.01; AI model vs. Fcal p>0.05). When we excluded rectal sparing cases (20, 6.8%), the mean AUROC of AI model increased to 0.85±0.05 (p=0.0007). Accuracy, sensitivity and specificity of AI model for predicting endoscopic activity in all patients and without rectal sparing cases were 0.739, 0.643, and 0.826, and 0.798, 0.711, and 0.872, respectively. Conclusion Stool photos of UC patients with deep learning technology demonstrated similar accuracy to Fcal in speculating endoscopic activity with better accuracy in patients without rectal sparing. The potential of simple stool pictures as a possible monitoring tool for UC activity is hopefully presented in this study.

P130 Intestinal ultrasound combined to fecal calprotectin is effective to predict endoscopic mucosal healing in ulcerative colitis: a cross-sectional study

Abstract Background In the “treat-to-target” era, the development of non-invasive markers to assess endoscopic healing in ulcerative colitis (UC) is essential. Fecal calprotectin (FC) and intestinal ultrasound (IUS) are alternatives to colonoscopy to assess UC activity. The objective of this study was to evaluate the performance of IUS and FC to assess endoscopic mucosal healing in UC patient. Methods All consecutive patients between January 2021 and August 2022 with UC who underwent (1) a complete colonoscopy (2) an intestinal ultrasound and/or (3) a fecal calprotectin (4) within 4 weeks were included in a prospective cohort. Bowel wall thickness (BWT) and color doppler signal (CDS) were assessed on each segment. Endoscopic mucosal healing was defined by a MAYO score of 0-1. Results A total of 57 patients were included, 57.9% had endoscopic healing (22/57 MAYO 0 and 11/57 MAYO 1). Thirty-two (56.1%) were female, the median age and disease duration were respectively 43 years (IQR, 30-58) and 29 years (IQR, 18-39). Respectively 16 (16/57, 28.1%) and 41 (41/57, 71.9%) patients had BWT < 3 mm and an absence of Doppler signal. The sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of BWT < 3 mm to predict endoscopic mucosal healing were 37%, 77%, 72% and 44%. The association of the absence of CDS with normal BWT did not modify these performances. The same values for fecal calprotectin < 150 µg/g were respectively 81%, 78%, 84% and 74%. The association of a fecal calprotectin < 150 µg/g, with a BWT < 3mm and the absence of Doppler signal increased the specificity and the PPV (Se 33%, Sp 94%, PPV 89%, VPN 48%). The same values were found for patients classified as MAYO 0 or MAYO 0-1 (Table 1). Conclusion The combination of intestinal ultrasound and fecal calprotectin is effective to identify endoscopic mucosal healing in UC.

REAL-WORLD USTEKINUMAB PERSISTENCE IN PATIENTS WITH ULCERATIVE COLITIS ATTAINING THE MAINTENANCE PHASE

Abstract BACKGROUND Sustained use of biologics and small molecule/advanced therapy has proven to be effective for controlling disease activity in ulcerative colitis (UC). The anti-interleukin agent ustekinumab was recently approved for UC in 2019. This study aimed to describe real-world ustekinumab persistence among patients with UC attaining the maintenance phase. METHODS Adults with UC selected from the Komodo Health’s comprehensive dataset had the first claim for ustekinumab (index date) between 10/21/2019 and 08/13/2021. Patients had ≥12 months of continuous insurance eligibility pre-index (baseline period), ≥1 claim with a diagnosis of UC at baseline or on the index date and persisted to their first subcutaneous ustekinumab claim (maintenance phase). Patients with diagnoses for other immune disorders at baseline or diagnoses for Crohn’s disease at any time were excluded. Persistence to ustekinumab was defined as absence of a therapy exposure gap of >120 days between days of supply or end of follow-up. Composite endpoints were persistence while being corticosteroid-free (no corticosteroids with ≥14 days of supply after day 90 post-index), and persistence while on monotherapy (no immunomodulators/non-index biologics or advanced therapies). Persistence endpoints were described post-maintenance phase until the earlier of 12 months, end of insurance eligibility, or data. Kaplan-Meier curves were used to assess persistence outcomes in all patients and among patients without prior biologic/advanced therapy exposure pre-index (bio-naïve). RESULTS 778 patients attaining the ustekinumab maintenance phase were selected, 236 (30.3%) were bio-naïve (Fig. 1). Mean follow-up time post-index was 13.5 months overall and 12.7 months for bio-naïve patients. By 12 months post-maintenance, 73.2% of all patients and 75.5% of bio-naïve patients were persistent to ustekinumab (Fig. 2). Additionally, amongst patients who were persistent and corticosteroid-free between the index date and the start of maintenance phase, 47.0% of all patients and 55.1% of bio-naïve patients remained persistent and corticosteroid-free 12 months after their first maintenance claim. Further, among patients who were persistent on monotherapy at the start of maintenance phase, 63.6% of all patients and 68.1% of bio-naïve patients remained persistent on monotherapy at 12 months. CONCLUSIONS In this study, 12 months after their first ustekinumab maintenance claim for UC, most patients who attained the maintenance phase were persistent to treatment, around half of patients who were also corticosteroid-free at the start of the maintenance phase remained persistent and corticosteroid-free, and most patients who were persistent on monotherapy at the start of the maintenance phase remained persistent on monotherapy.

METHODS TO DERIVE A MODIFIED MAYO SCORE FROM ELECTRONIC HEALTH RECORDS DATA

Abstract BACKGROUND The modified Mayo Score (MMS), which consists of stool frequency, rectal bleeding, and endoscopic subscores, is the most commonly used method for measuring disease activity in Ulcerative Colitis (UC) patients. It is a standard outcome measure in clinical trials, and is recommended as a clinical trial endpoint by the US Food and Drug Administration. Each component has a score from 0-3; the total MMS ranges from 0 to 9. MMS is infrequently recorded in routine care, in part because it requires an endoscopic assessment. Real world data, including electronic health record (EHR) databases, are useful for studying longitudinal disease and treatment outcomes, but most EHR databases do not include Mayo scores. Building off the methods described by Rudrapatna et al., 2021, we calculated a derived MMS using data elements available in EHRs. METHODS Data were derived from the OM1 PremiOM UC Dataset (OM1, Boston, MA), a multisource real-world database with linked healthcare claims and EHR data on US patients with UC (2013-present). Each of the three subscores was extracted from clinical notes and endoscopy reports, either by automated natural language processing methods or by abstraction by a trained medical abstractor. Rectal bleeding and stool frequency scores occurring within 4 months before or up to 1 month after the endoscopic score were combined to calculate a MMS. Multiple MMSs could be calculated for each patient, but each component score could contribute to only one MMS. RESULTS Among 12,849 UC patients, only 38 had a full Mayo score recorded in their notes, and 1 had a modified Mayo recorded. After applying the above algorithm, we were able to calculate a derived MMS for 739 patients. 220 patients had > 1 score available. Figure 1 shows the distribution of derived MMSs. Patients with a MMS were younger and more likely to be Asian, more likely to be treated with biologic therapies and less likely to be treated with mesalamine compared with those who could not have a MMS calculated (Table 1). CONCLUSIONS A derived MMS can be calculated from data that may be recorded in the medical record. Further work to validate these measures against a gold standard should be considered, but was not feasible in the OM1 dataset due to the paucity of observed Mayo scores in EHR data. Increased emphasis on standardized collection of relevant information in EHR systems would further improve the availability of derived MMSs. The population for which a MMS can be derived may have more severe disease and more frequent interactions with the healthcare system as evidenced by higher proportion of patients prescribed biologic therapies. MMSs can be derived and used to describe UC patients and could potentially be used to study longitudinal changes in patient disease status and treatment effectiveness in settings where observed scores are not available.

QUANTITATIVE AND EXPLAINABLE ARTIFICIAL INTELLIGENCE (AI)-POWERED APPROACHES TO PREDICT ULCERATIVE COLITIS DISEASE ACTIVITY FROM HEMATOXYLIN AND EOSIN (H&E)-STAINED WHOLE SLIDE IMAGES (WSI)

Abstract BACKGROUND Microscopic inflammation has been shown to be an important indicator of disease activity in ulcerative colitis (UC). However, manual histologic scoring is semi-quantitative and subject to interobserver variation, and AI-based solutions often lack interpretability. Here we report two distinct quantitative approaches to predict disease activity scores and histological remission using AI-powered digital pathology. Both the random forest classifier (RFC) and graph neural network (GNN) further provide explainability and biological insight by identifying histological features informing model predictions. METHODS Convolutional neural networks (CNNs) were developed using >162k annotations on 820 WSI of H&E-stained colorectal biopsies for pixel-level identification of tissue regions (e.g. crypt abscesses, erosion/ulceration) and cell types (e.g. neutrophils, plasma cells). All WSI were scored by 5 board-certified pathologists using the Nancy Histological Index (NHI) to establish consensus ground truth. A rich, quantitative set of human interpretable features that capture CNN predictions of the tissue region and cell type across each WSI was extracted and used to train a RFC to predict slide-level NHI score. To test the hypothesis that tissue region spatial relationships and cellular composition can inform AI-based predictions of disease activity, a separate GNN was trained, using nodes defined by spatially-resolved CNN model-generated outputs, to predict NHI score. The RFC and GNN also predicted histologic remission (NHI<2). Feature importance was calculated for all combinations of RFC (Fig. 1), and the GNNExplainer was applied to locate important interactions between regions in the tissue and identify features significantly contributing to GNN predictions (Fig. 2). RESULTS The RFC and GNN both predicted histologic remission with high accuracy (weighted kappa 0.87 and 0.85, respectively). Both models also identified histologic features relevant to disease activity predictions. Some features are well established, e.g. infiltrated epithelium or neutrophil cell features distinguish cases with histologic remission. The models also identified features beyond those assessed by the NHI, e.g. area proportion of basal plasmacytosis associated with predictions of NHI 2 and 3. Other features not previously implicated in UC disease activity were also identified, e.g. intraepithelial lymphocytes differentiate cases with NHI 3. CONCLUSIONS We report quantitative and interpretable AI-powered approaches for UC histological assessment. CNN identification of UC histology was used as input to two distinct disease activity classifiers that showed strong concordance with consensus pathologist scoring. Both approaches provide interpretable features that explain model predictions and that may be used to inform biomarker selection and clinical development efforts.

GROWTH OUTCOMES OF IV ANTI-TNF BIOSIMILARS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Biosimilars are biologic products similar in safety and efficacy to the originator product. Tumor necrosis factor-alpha inhibitors (anti-TNFs) are used in the treatment of inflammatory bowel diseases (IBD). There are limited studies evaluating the long-term outcomes of anti-TNF biosimilars in children with IBD. Growth is an important clinical outcome, especially in childhood-onset IBD. However, no study to date has compared growth outcomes in patients initiated on the IV anti-TNF originator as compared to a biosimilar. METHODS This was a single-center retrospective review of patients with IBD, younger than 16 years old, and initiated on the IV anti-TNF originator or a biosimilar between April 2016 and February 2021 at Nationwide Children’s Hospital. To be eligible for the study and evaluate the primary outcome, patients must remain on the IV anti-TNF therapy for at least 12-months. We used propensity score methodology to identify 37 pairs of matched patients based on baseline characteristics (age of anti-TNF initiation, disease (CD vs UC/IC), behavior, location, perianal type, race). Demographic data, laboratory values, disease activity scores, and growth values (z-scores were recorded for weight, height, and BMI) were collected at baseline (prior to anti-TNF initiation) and 6-months and 12-months post initiation. Linear mixed models with random intercepts accounting for within patient correlation of measurements were fit to test differences in measures over time and between study groups. Hypothesis testing was conducted at an alpha of 0.05 to be used for all statistical analyses. RESULTS There were 113 patients on the originator and 39 patients on a biosimilar who met our eligibility criteria. Nineteen percent of patients on the originator and 16% of patients on a biosimilar were excluded from analysis due to discontinuing the IV anti-TNF agent prior to 12 months. Weight, height, and BMI z-scores increased over time (from baseline to 12-months) for both groups (p<0.05). There was not a significant difference in the rate of change for weight, height, or BMI z-scores between study groups. Clinical outcomes of lab values (albumin, c-reactive protein, and hemoglobin) were not statistically different in the rate of change from baseline to 12-months between patients initiated on the originator or biosimilar. There also was not a significant difference in the pediatric Crohn’s disease activity index, pediatric ulcerative colitis activity index, or the physician global assessment between patients initiated on the biosimilar or originator from baseline to 12-months. CONCLUSIONS There were similar improvements in growth and clinical outcomes in patients initiated on the IV anti-TNF originator compared to a biosimilar agent. This is the first study to evaluate whether anti-TNF biosimilars have similar growth outcomes in children with IBD.

International Consensus on Definition of Mild-to-Moderate Ulcerative Colitis Disease Activity in Adult Patients.

Background and Objectives: At present, there is no consensus definition of mild-to-moderate disease activity in patients with ulcerative colitis. The objective of the present study was to establish a reliable definition of mild-to-moderate disease activity in adult patients with ulcerative colitis. Materials and Methods: Twelve physicians from around the world participated in a virtual consensus meeting on 26 September 2022. All the physicians had expertise in the diagnosis and treatment of inflammatory bowel disease. After a systematic review of the literature and expert opinion, a modified version of the RAND/University of California, Los Angeles appropriateness method was applied. A total of 49 statements were identified and then anonymously rated (on a 9-point scale) as being appropriate (scores of 7 to 9), uncertain (4 to 6) or inappropriate (1 to 3). The survey results were reviewed and amended before a second round of voting. Results: Symptom and endoscopic-based measurements are of prime importance for assessing mild-to-moderate ulcerative colitis activity in clinical trials. The experts considered that clinical activity should be assessed in terms of stool frequency, rectal bleeding and fecal urgency, whereas endoscopic activity should be evaluated with regard to the vascular pattern, bleeding, erosions and ulcers. Fecal calprotectin was considered to be a suitable disease activity marker in mild-to-moderate ulcerative colitis. Lastly, mild-to-moderate ulcerative colitis should not have more than a small impact on the patient's daily activities. Conclusions: The present recommendations constitute a standardized framework for defining mild-to-moderate disease activity in clinical trials in the field of ulcerative colitis.

Nutritional Status Indicators as a Predictor of Achieving Remission at Week 14 during Vedolizumab Therapy in Patients with Ulcerative Colitis: A Pilot Study.

Background: The loss of response or failure to achieve remission to vedolizumab in ulcerative colitis (UC) patients is currently a major clinical problem. Recently, Nutritional Risk Index (NRI), Controlling Nutritional Status (CONUT), and Malnutrition Universal Screening Tool (MUST) have been suggested as a new prognostic factor of UC activity. Here, we aimed at confirmation of hypotezis that NRI, CONUT and MUST may be used as inexpensive and efficient predictive biomarkers of response in UC patients treated with vedolizumab. Methods: This study was conducted in retrospective manner in 32 adult patients with UC of Caucasian origin (21 men and 11 women), who were qualified for 52-week therapy with vedolizumab and finished the 14-weeks from January 2020 to March 2022. Our study analyzed the 45 courses of vedolizumab therapy. Nutritional status indicators, i.e., the NRI, CONUT and MUST of each UC patient, were marked at the time of qualifying for biological treatment. Results: In our study, the MUST score was significantly lower in UC patients who positively achieved clinical remission at week 14 during vedolizumab induction therapy (0.33 ± 0.49 vs. 1.37 ± 0.83; p = 0.002). The analysis showed the lower baseline NRI and CONUT scores in patients with positive clinical remission at week 14 (NRI: 96.42 ± 4.29 vs. 101.41 ± 7.09; p = 0.024; CONUT: 1.00 ± 1.08 vs. 2.16 ± 1.46; p = 0.031). Conclusions: Nutritional status indicators (NRI, MUST and CONUT) may become valuable predictor of achieving remission at week 14 during vedolizumab therapy in UC patients.

Associations between Pouchitis and Fecal Calprotectin after Restorative Proctocolectomy in Patients with Ulcerative Colitis

Introduction: Recently, fecal calprotectin has been identified and used as an assessment tool for the confirmation of disease activity in ulcerative colitis. Although a meta-analysis suggested the usefulness of fecal calprotectin for the assessment of pouchitis, the number of participants was still insufficient. Therefore, we prospectively measured fecal calprotectin levels during pouchoscopy and analyzed their associations with pouchitis. Methods: Patients who underwent pouchoscopy after total proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis were included. Fecal samples were collected for the measurement of calprotectin during pouchoscopy. Patients either with or without suspicious pouchitis were included. Pouchitis was defined as a modified pouchitis disease activity index (m-PDAI) score of ≥5. The associations between the development of pouchitis and the m-PDAI score and fecal calprotectin and serum markers, including C-related protein, albumin, and white blood cells, were assessed. Results: A total of 170 patients were included. Seventy-two patients were diagnosed with pouchitis with an m-PDAI score of 7.3 ± 1.5. The values of fecal calprotectin were 1,500 ± 1,544 μg/g in patients with pouchitis and 259 ± 402 μg/g in patients without pouchitis (p < 0.01). The correlation coefficient between calprotectin and the m-PDAI score was significant (r² = 0.279, p < 0.001). The cutoff value of fecal calprotectin in receiver operating characteristic analysis was 246 μg/g (area under curve 0.85, sensitivity 83.9%, specificity 71.0%). Fecal samples were able to be collected from 6 patients. The levels of fecal calprotectin significantly decreased from 2,101.3 ± 880.3 μg/g to 284.2 ± 96.9 μg/g in response to the treatment. Conclusions: Elevated fecal calprotectin appeared to be significantly correlated with pouchitis. We should consider the alteration of this marker during treatments in further studies.

Fecal Calgranulin C a Novel Noninvasive Marker in Predicting Activity and Severity of Ulcerative Colitis Compared with Colonoscopy.

Fecal Calgranulin C a Novel Noninvasive Marker in Predicting Activity and Severity of Ulcerative Colitis Compared with Colonoscopy.

Fecal Calprotectin as a Disease Activity and Prognostic Marker in Ulcerative Colitis

Fecal Calprotectin as a Disease Activity and Prognostic Marker in Ulcerative Colitis

The role of immune modulatory CD163+ macrophages and FOXP3+ T regulatory lymphocytes in ulcerative colitis

Abstract Background Recently, research work was intensified to explore the role of the immune microenvironment in different diseases. The inflammatory Bowel Disease- Distribution, Chronicity, Activity score (IBD-DCA) is now accepted as a practical reproducible tool for assessment of the histologic inflammatory burden and histologic mucosal healing in ulcerative colitis (UC) endoscopic biopsies. The particular contribution of immune modulatory CD 163+ macrophages and FOXP3+T regulatory lymphocytes (T-regs), and their implication in UC pathogenesis and course are still not clearly elaborated. Correlation between these attributes and the histologic indices would offer valuable insights that could help tailor the management plan on a personalized medicine protocols level, in addition to paving roads to new therapeutic target modalities. Aim of the study Evaluate the role of immune modulatory CD163+ macrophages and FOXP3+ T regulatory lymphocytes in ulcerative colitis and correlate their immunohistochemical expression with the pathological parameters of Inflammatory Bowel Disease- Distribution, Chronicity, Activity score (IBD-DCA score). Materials and methods Paraffin-embedded tissue sections from 60 cases of endoscopic colonic biopsies diagnosed as ulcerative colitis were immunohistochemically studied for CD163 and FOXP3 expression and graded semi-quantitively. Furthermore, histopathological features were evaluated according to IBD-DCA score and correlated with CD163 and FOXP3 expression for statistical analysis. Results CD163+ macrophages and FOXP3+ T-regs were demonstrated in 100% (60/60) and 78% (47/60) respectively of the lamina propria of ulcerative colitis cases. Significant correlation with activity (A) parameter of DCA-score and architectural distortion of detailed chronicity parameter for both markers was detected. Additionally, CD163 immuno-expression showed significant correlation with detailed activity parameters while FOXP3 presented a significant correlation with the chronicity parameter of DCA score. Conclusion The immune modulatory CD 163+ macrophages and FOXP3+T-regs represent key players in mucosal tissue inflammation, disease activity and chronicity in UC. This could offer new therapeutic modalities targeting the players of the immune microenvironment that should be deeply investigated in future studies.

Combined effects of granulocyte and monocyte adsorption apheresis and corticosteroids on ulcerative colitis.

Several new treatments for ulcerative colitis have been developed recently. The depletion of leukocytes by granulocyte and monocyte adsorption apheresis (GMA) was developed and adapted for patients with ulcerative colitis with rare adverse events. We investigated whether treatment with GMA and prednisolone (GMA + PSL) is more effective than PSL alone for patients with moderate to severe ulcerative colitis. Forty-seven patients with moderate to severe ulcerative colitis were retrospectively analyzed. Among the 47 patients, 27 received PSL, while 20 received GMA + PSL. The clinical activity of ulcerative colitis was evaluated using the Lichtiger clinical activity index (CAI) and serum levels of C-reactive protein. Mayo endoscopic score (MES) was used to examine endoscopic activity. The clinical remission rate was significantly higher in the GMA + PSL group than in the PSL group (65% vs 29.6%, p = 0.0206). The mucosal healing rate was also significantly higher in the GMA + PSL group than in the PSL group (60% vs 26%, p = 0.0343). The combination of GMA and steroids may be more effective than steroids alone for inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

Milan Ultrasound Criteria Predict Relapse of Ulcerative Colitis in Remission

Introduction: Bowel ultrasound is a noninvasive alternative to endoscopy for assessing the disease activity of ulcerative colitis; however, it is unclear whether bowel ultrasound can predict subsequent relapse from remission. Materials and Methods: A retrospective cohort study enrolled patients with ulcerative colitis who underwent bowel ultrasound between July 2018 and July 2021 during clinical remission (patient-reported outcome-2 ≤1 and no rectal bleeding) for at least 3 months and were followed up for 1 year. Ultrasonographic findings (bowel wall thickness, bowel wall flow, bowel wall stratification, and enlarged lymph nodes), Milan ultrasound criteria, Mayo endoscopic subscore, C-reactive protein, and fecal calprotectin levels and their association with subsequent clinical relapse were assessed. Relapse was defined as rectal bleeding score ≥1, stool frequency score ≥2, or treatment intensification for symptoms. Results: 31% of the patients (18/58) relapsed within 1 year. No single ultrasonographic finding predicted relapse, whereas Milan ultrasound criteria >6.2 (p = 0.019), Mayo endoscopic subscore ≥1 (p = 0.013), and fecal calprotectin ≥250 μg/g (p = 0.040) were associated with a shorter time to relapse in the log-rank test. Milan ultrasound criteria >6.2 (hazard ratio 3.22; 95% confidence interval 1.14–9.08, p = 0.027) and Mayo endoscopic subscore ≥1 (hazard ratio 8.70; 95% confidence interval 1.11–68.1, p = 0.039) showed a higher risk of relapse according to a Cox proportional hazards model. Conclusion: Bowel ultrasound can predict subsequent clinical relapse from remission in patients with ulcerative colitis using the Milan ultrasound criteria.

Novel Utility of Leucine-Rich Alpha-2-Glycoprotein as a Biomarker in Ulcerative Colitis: A Predictor of Endoscopic Remission Independent of Symptoms

Introduction: Leucine-rich alpha-2-glycoprotein (LRG) is a potential biomarker for disease activity and reflects mucosal healing in patients with ulcerative colitis (UC). However, only a few studies have described a detailed sensitivity analysis of LRG in predicting mucosal healing in patients. This study aimed to evaluate the association between LRG and the endoscopic activity of UC and its predictability for mucosal healing and explore the utility and clinical application of LRG. Methods: The diagnostic accuracy of biomarkers, including LRG, in predicting the endoscopic activity of UC was evaluated. All consecutive patients who underwent total colonoscopy between April 2021 and September 2022 were included. The Mayo endoscopic subscore (MES) was used for assessing endoscopic activity. Furthermore, endoscopic remission was defined as an MES of ≤1. Clinical activity was evaluated based on stool frequency and bloody stool. Receiver operating characteristic curve analysis and binary logistic regression were performed to assess the diagnostic accuracy of the biomarkers. We evaluated LRG trends and treatment response in patients with MES ≥2 who underwent induction therapy. Results: This study comprised 214 patients. The proportions of endoscopically and clinically active patients were 33.6% and 49.1%, respectively. LRG had an area under the curve (AUC) of 0.856, with a higher diagnostic accuracy than other biomarkers, such as C-reactive protein, leukocyte, neutrophil, platelet, and albumin. The cutoff value for LRG was 15.6 μg/mL (sensitivity, 72.2%; specificity, 86.6%). Using the MES, patients with higher scores had higher LRG levels than those with lower scores. The cutoff value, AUC, sensitivity, and specificity varied with a higher AUC for left-sided colitis and pancolitis than for proctitis. Logistic regression analysis showed that LRG was an independent predictor of endoscopic remission using multivariate analysis, even with the factor of clinical activity. The change ratio of LRG pre- and post-treatment was statistically significant in the higher LRG group. Conclusion: LRG reflected endoscopic activity independently, regardless of clinical symptoms. An LRG below the cutoff value could indicate a significantly low probability of endoscopic activity in asymptomatic patients, and follow-up endoscopy (not for cancer screening) may be unnecessary. Furthermore, a higher LRG level might be more useful as an indicator of treatment efficacy.

Gut metabolomic profiles in paediatric ulcerative colitis patients prior to and after receiving faecal microbiota transplants.

Ulcerative colitis (UC) is an immune-mediated inflammation of the colonic mucosa. Gut microbiota dysbiosis may play a significant role in disease pathogenesis by causing shifts in metabolomic profiles within the gut. To identify differences and trends in the metabolomic profile of paediatric UC patients pre- and post-faecal microbiota transplants (FMT). Forty-six paediatric patients with mild-to-moderate UC and 30 healthy paediatric patients were enrolled in this study. Baseline stool samples were collected prior to FMT initiation and at months 1, 3, 6, and 12 post-FMT. Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at baseline and months 1, 3, 6, and 12 after FMT. The average Bray-Curtis dissimilarities to healthy subjects decreased after FMT. In principal coordinate analysis plots, UC patients' centroids drew nearer to healthy individuals. The variance explained by phenotype (Healthy versus UC) reduced and remained significant. From 1 to 3 months after FMT, PUCAI trends were statistically significant and decreasing. PUCAI scores remain flat starting 6 months after FMT. This study concludes that paediatric UC patients have a significantly different baseline metabolite profile than healthy controls. Although being time limited, FMT significantly altered these metabolite profiles and shifted them towards that of healthy controls.