Cases Of Colitis Research Articles

Implementation of a robotic surgical practice in inflammatory bowel disease.

Robotics adoption has increased in colorectal surgery. While there are well-established advantages and standardised techniques for cancer patients, the use of robotic surgery in inflammatory bowel disease (IBD) has not been studied yet. To evaluate the feasibility and safety of robotic surgery for IBD patients. Prospectively data in IBD patients having robotic resection at Guy's and St Thomas' hospital. All resections performed by a single colorectal surgeon specialised in IBD, utilising DaVinci platform. July 2021 to January 2023, 59 robotic IBD cases performed, 14 ulcerative colitis (UC) and 45 Crohn's disease (CD). Average age; CD patients 35, UC 33years. Average Body mass index (BMI); 23 for CD and 26.9 for UC patients. In total, we performed 31 ileo-caecal resections (ICR) with primary anastomosis (18 Kono-S anastomosis, 6 mechanical anastomosis and 7 ileo-colostomy), of those 4 had multivisceral resections (large bowel, bladder, ovary). Furthermore, 14 subtotal colectomy (1 emergency), 8 proctectomy, 3 panproctocolectomy and 3 ileoanal J pouch. 18 of the 45 patients (45.0%) with Crohn's disease had ongoing fistulating disease to other parts of the GI tract (small or large bowel). ICR were performed using different three ports position, depending on the anatomy established prior to surgery with magnetic resonance images (MRI). One patient had conversion to open due to anaesthetic problems and one patient required re-operation to refashion stoma. 98.0% cases completed robotically. Median Length of hospital stay (LOS) was 7days for CD and 7 for UC cases, including LOS in patients on pre-operative parenteral nutrition. Robotic colorectal techniques can be safely used for patients with IBD, even with fistulating disease. Future research and collaborations are necessary to standardize technique within institutions.

UNIQUE MONOCYTE EXPRESSION SIGNATURE IN A STXBP2 MUTATION CAUSING INFANTILE ONSET VEO-IBD AND HLH

Abstract Mutations in syntaxin-binding-protein-2 (STXBP2) can result in NK cell dysfunction leading to a hyperinflammatory state including familial HLH and infantile onset inflammatory bowel disease (IBD). While the function of STXBP2 in NK cells and cytotoxic T cells has been well described, it is highly expressed in monocytes with unclear relevance. We report the case of an infant who presented with severe infantile onset diarrhea with an identified pathogenic mutation in STXBP2. We sought to utilize scRNA-Seq to study the impact of STXBP2 deficiency on monocyte transcription, with the goal of generating insight into the pathogenesis of disease. METHODS: Trio whole exome sequencing was performed. PBMCs were collected from the described patient (case), and two control groups: 3 patients with VEO-IBD, and 3 age matched healthy controls. Single cell RNA-Seq was performed using the 10x platform and data analysis was done using Seurat in R. RESULTS: A male infant presented at 1 week of age with diarrhea and metabolic acidosis. Endoscopic evaluation at 4 weeks of age showed histologic findings of colitis and marked epithelial cell changes, including cell rounding. WES identified a homozygous pathogenic mutation in STXBP2. Due to significant risk of HLH, he underwent evaluation for stem cell transplant. However, in the interim he developed severe HLH requiring ICU level care. He recovered following aggressive treatment and underwent HSCT at 4 months of age and retransplant for graft failure at 11 months of age. He is currently in endoscopic remission off therapy. We analyzed PBMCs from the case patient using single cell RNA-Seq, as compared to patients with VEO-IBD and age-matched controls. STXBP2 expression was most enriched in monocyte populations and reduced in the case patient compared to controls. 231 and 187 genes were differentially expressed in the case monocytes as compared to both controls. The case patient had a paucity of non-classical monocytes. Within the classical monocytes, differentially expressed genes showed enrichment of host defense, cytokine processes, and apoptotic processes. Within the intermediate monocytes, differentially expressed genes showed enrichment of chemotaxis pathways, antigen presentation and T cell activation processes. CONCLUSIONS: Mutations in STXBP2 are a life-threatening cause of fHLH and infantile onset IBD. We report a case of infantile onset IBD due to a homozygous mutation in STXBP2 with resolution of disease post HSCT. Transcriptional analysis of PBMCs from this patient reveals a paucity of non-classical monocytes in the peripheral blood, and differential regulation of genes implicated in host defenses, antigen presentation, chemotaxis and apoptosis. These results may suggest the role of monocyte function in pathogenesis of STXBP2 and in other forms of IBD.

UPADACITINIB RESOLVES DIARRHEA AND FECAL CALPROTECTIN ABNORMALITIES IN BUDESONIDE-DEPENDENT MICROSCOPIC COLITIS

Abstract BACKGROUND Current American Gastroenterological Association guidelines are devoid of recommendations for steroid and biologic refractory microscopic colitis (MC). Upadacitinib (UPA) is a small molecule that selectively inhibits janus kinase-1 (JAK1). Evidence pertaining to its utility in the management of steroid and biologic refractory MC remains limited. Herein, we report efficacy and safety of UPA in medically refractory MC. METHODS Three patients presenting with severe MC refractory to budesonide and biologic therapy (vedolizumab, Table 1) were treated with standard UPA therapy. UPA was initiated at standard induction of 45 mg/day for 8 weeks. All patients had their UPA reduced to 30 mg/d for maintenance. Therapeutic response was assessed using Hjortswang’s criteria (HC), and serial fecal calprotectin measurements. HC defines clinical remission as < 3 bowel movements (BM)/day and < 1 watery stools/day. Active disease was defined as ≥ 3 BM/day or ≥1 watery stool/day. FC < 150 ug/g was deemed normal. RESULTS Three patients (Table 1) were included in this study. Overall, our cohort had 2 cases of collagenous colitis and 1 case of lymphocytic colitis. Two patients had an association with diagnosis of celiac disease. All patients failed steroid and biologic therapy (Table 1) with an average of 5 failed medications. At the end of UPA induction, all patients attained < 3 BM/day (% reduction: -79%±6). Resolution of abdominal pain, nocturnal stooling, fatigue and fecal urgency were observed. As per HC, 1 patient displayed clinical remission and two achieved significant symptomatic improvement (Table 2). All patients displayed significant reductions in FC (-71%±1.5). At 16 weeks, none of the patients experienced LBM (-100%±0) and all resolved abdominal pain, nocturnal stooling, fatigue and fecal urgency (Table 2). FC normalized (-93%±6.4) in all three patients (Table 3). No serious infections, cardiovascular events or thromboembolic events occurred. One patient experienced gout and required further UPA dose reduction to 15 mg/day. This patient continues to maintain remission at 15 mg/day. DISCUSSION UPA is a novel JAK1 inhibitor with a favorable pharmacokinetic profile. It’s rapid onset of action and relative safe profile compared to chronic steroid use makes it an ideal treatment for refractory MC. The pathophysiology of MC remains poorly elucidated. It is postulated that JAK1 is involved in IL-2, IL-4, IL-6, IL-15 and IFN signaling. UPA-inhibited JAK-STAT ameliorates IFN-γ and IL-6, implicated in MC pathogenesis. Data here supports UPA use in steroid and biologic refractory MC. Further large-scale studies are warranted to delineate long term efficacy and safety of UPA in MC. Table 1 Demographics and Baseline Disease Characteristics. Table 2 Trends in clinical parameters at baseline versus Weeks 8 and 16 Table 3 Percentage reduction in loose bowel movements (LBM) and fecal calprotectin (FC)

SOCIOECONOMIC DISPARITIES IN HOSPITALIZATION AND OUTCOMES OF EOSINOPHILIC COLITIS: A FIVE-YEAR NATIONAL ANALYSIS

Abstract BACKGROUND Eosinophilic colitis (EoC) is a rare gastrointestinal inflammation of the colon due to an altered hypersensitivity reaction characterized by eosinophilic infiltration into the colonic wall. Patients usually present with abdominal pain, diarrhea, and weight loss. METHODS We used the National Inpatient Sample (NIS) database to conduct a retrospective study of hospitalized adult patients with eosinophilic colitis using the validated ICD-10 diagnosis codes between January 1, 2016, and December 31, 2020. RESULTS We identified 4353 cases of eosinophilic colitis using the NIS database. There were 748, 776, 889, 934, and 1,006 eosinophilic colitis cases diagnosed in 2016, 2017, 2018, 2019, and 2020 respectively. Males were more likely to be hospitalized due to eosinophilic colitis than females (51.8% vs. 48.2%). Moreover, there was a significantly higher prevalence of eosinophilic colitis among the white population, with 81.7% in Whites, 8.1% in Blacks, 6.3% in Hispanics, and 1.3% in Asians. 26.5% of those patients had Medicare, 15.7% had Medicaid, and 50.6% had private/HMO insurance. About 20.7% of patients had a median household income of $45,999 or less, 23.6% had $46,000-58,999, and 55.6% had $59,000 or more. Based on hospital location, 30.3% of the cases were in the South, 27.5% in the Midwest, 23.4% in the West, and 18.8% in the Northeast. The majority of patients admitted for eosinophilic colitis were recorded in urban teaching hospitals (77.8%) compared to 17.6% in urban nonteaching hospitals and 4.6% in rural areas. Only 16.5% of the patients with eosinophilic colitis had a Charlson Comorbidity Index of 3 or higher. CONCLUSION Based on the national inpatient sample over 5 years, males and whites are more likely to be hospitalized with eosinophilic. The report suggests that eosinophilic colitis is common among patients with high median household income and has a better prognosis.

FREE AIR FROM WHERE? SPONTANEOUS PNEUMOMEDIASTINUM AND SUBCUTANEOUS EMPHYSEMA IN A PATIENT WITH ULCERATIVE COLITIS IN THE ABSENCE OF COLONIC OR ESOPHAGEAL PERFORATION

Abstract INTRODUCTION The development of Spontaneous Pneumomediastinum and Subcutaneous Emphysema in patients with Inflammatory Bowel Disease (IBD) has often been associated with perforation related to toxic megacolon or prior endoscopic procedures. We describe a case of Ulcerative Colitis complicated by Clostridium difficile (C diff) colitis in which Spontaneous Pneumomediastinum and Subcutaneous Emphysema developed without any evidence of perforation. CASE REPORT A 20-year-old male with a past medical history of recently diagnosed Ulcerative Colitis presented for evaluation of rectal pain, dysphagia, hematochezia, fecal incontinence, and urinary hesitancy. He endorsed dysphagia with the inability to tolerate solids or liquids for 4 days. He was diagnosed with Ulcerative Colitis 5 months prior to presentation and had unintentionally lost 90 lbs over the past 2 months. His home medication regimen included infliximab started 2 weeks prior, mesalamine PO tablets and suppositories, and a prednisone taper initiated at 10 mg TID. Laboratory tests confirmed anemia, leukocytosis, thrombocytosis, and elevated ESR and CRP levels. Chest X-ray and CT scans of the neck and chest showed moderate pneumomediastinum and subcutaneous emphysema. Given the symptoms of dysphagia along with the imaging findings of pneumomediastinum and subcutaneous emphysema, there was concern for esophageal perforation. However, an Esophagram and Upper GI series were both unremarkable. Abdominal CT revealed colitis of the descending and sigmoid colon without any evidence of free air or free fluid. Fecal Occult Blood Test and C diff antigen and toxin assays were positive. He was treated with oral vancomycin, IV fluids, IV methylprednisolone, and total parenteral nutrition (TPN). His symptoms significantly improved with a decrease in stool frequency and bloody stools. TPN was weaned and he was able to tolerate an oral diet. A repeat CT scan of the chest showed a complete resolution of the pneumomediastinum. CONCLUSION There are only a few reported cases in the literature of spontaneous pneumomediastinum and subcutaneous emphysema in patients with IBD in the absence of colonic or esophageal perforation. The spontaneous isolated presentation of air leaking from a chronically diseased hollow organ remains rare. In our patient there was no evidence of perforation, therefore the pneumomediastinum and subcutaneous emphysema likely resulted from the release of free air from colonic micro-perforations caused by the severe inflammation related to his Ulcerative Colitis flare and C. diff infection. CT Chest demonstrating pneumomediastinum and subcutaneous emphysema of the neck CT Neck demonstrating subcutaneous emphysema

MACHINE LEARNING CLASSIFICATION OF THE EPIDEMIOLOGIC STAGES OF INFLAMMATORY BOWEL DISEASE ACROSS GEOGRAPHY AND TIME

Abstract BACKGROUND Epidemiologic stages of inflammatory bowel disease (IBD) have been proposed: 1. Emergence (low incidence and prevalence); 2. Acceleration in Incidence (rapidly rising incidence, low prevalence); and 3. Compounding Prevalence (stabilizing incidence, rapidly rising prevalence). To date, these stages have been theoretical without quantified definitions of incidence and prevalence. AIM To use machine learning to determine incidence and prevalence ranges corresponding to the epidemiologic stages and provide stage classifications across time for global regions. METHODS We built a supervised random forest classifier in R to determine epidemiologic stages of IBD from population-based studies (n=340), a subset derived from a systematic review on the incidence and prevalence of IBD. A labelled training data set comprising rates of incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC) extracted from the systematic review was used to predict classifications of stage 1, stage 2, or stage 3 for each region, stratified by decade (1960–2019). Model accuracy was measured using a blind validation data set. The validated model was then used to predict stage classifications for regions in the data set. Interquartile ranges for incidence and prevalence of CD and UC were calculated on the random forest output, and the distributions were compared using negative binomial regression. RESULTS The random forest’s classification accuracy on the blinded validation data was 93.7% (95%CI: 90.6, 96.1) indicating an appropriate model fit and performance. Significant differences between all stages for the incidence and prevalence of CD and UC (p<0.001) were found. The clear distinction across stages defines the incidence and prevalence ranges (25th–75th, per 100,000) for IBD as: CD incidence 0.0–0.3, UC incidence 0.2–0.7, CD prevalence 0.3–2.2, and UC prevalence 1.7–8.1 for stage 1; CD incidence 1.0–4.4, UC incidence 2.3–6.3, CD prevalence 9.0–33.9, and UC prevalence 22.8–73.3 for stage 2; and CD incidence 6.6–14.0, UC incidence 10.1–18.1, CD prevalence 163.2–274.7, and UC prevalence 189.1–323.2 for stage 3 (Figure 1). A decade-by-decade analysis shows global regions transitioning across the epidemiologic stages (Figure 2). By the 2010s, North America, Scandinavia, Western Europe, Australia, and New Zealand were in stage 3. Most regions in Asia and Latin America were in stage 1 in the last half of the 20th century, with many transitioning to stage 2 in the 2010s. DISCUSSION Temporal incidence and prevalence data show that regions transition across epidemiologic stages. Numerical definitions of the epidemiologic stages can be used to establish the anticipated burden growth of IBD by providing estimated rates of the number of incident and prevalent IBD cases a region can expect as it transitions between IBD epidemiologic stages in the future. Figure 1 Coalescing ranges for incidence (panel A) and prevalence (panel B) by Crohn’s disease and ulcerative colitis at epidemiologic stage 1, stage 2, and stage 3. Data were categorized by data type (incidence or prevalence), disease type (Crohn’s disease or ulcerative colitis), and epidemiologic stage, as per results from the random forest classifier. The 25th and 75th percentiles were calculated using the rates across all regions included in the analysis for all available time points for each box group. Figure 2 Global maps depicting epidemiologic stages of IBD evolution from 1960 to 2019 broken down by decade, as predicted by the random forest model. Panel A contains stage classifications from 1960 to 1969; panel B contains stage classifications from 1970 to 1979; panel C contains stage classifications from 1980 to 1989; panel D contains stage classifications from 1990 to 1999; panel E contains stage classifications from 2000 to 2009; and panel F contains stage classifications from 2010 to 2019.

CLINICAL OUTCOMES OF INFLAMMATORY BOWEL DISEASE AFTER ORTHOTOPIC HEART TRANSPLANT

Abstract BACKGROUND Limited data are available on outcomes of patients with pre-existing inflammatory bowel disease (IBD) who undergo orthotopic heart transplantation (OHT) or develop de novo IBD post-OHT. We aimed to assess the incidence and disease outcomes of pre-existing and de novo IBD in OHT patients while evaluating the effect of IBD on OHT outcomes. METHODS A retrospective review of records was performed from a tri-site tertiary care system between July 2000 and July 2022. A total of 83 OHT receipients were concomitantly diagnosed with colitis of infectious or inflammatory etiology. Only patients with a diagnosis of IBD were included. Sub-analyses of the outcomes and immunosuppressive regimens of OHT recepients were done relative to those with pre-existing or de novo IBD. RESULTS A total of 8 OHT patients with concomitant IBD were identified. The median patient age (IQR) was 54 (23) with OHT and IBD onset at 50 (21.2) and 32.5 (15.7), respectively. Six patients were diagnosed with ulcerative colitis (UC) and 2 were diagnosed with Crohn’s disease. Five of the patients were female. All patients developed IBD within 11.5 (8) years within OHT. Only 1 patient developed de novo IBD 15 years after the first OHT and 7 years prior to a second OHT. OHT immunosuppressive regimens included a combination of tacrolimus (TAC) and prednisone (n=2), TAC and mycophenolate mofetil (MMF) (n=2), TAC, MMF, and sirolimus (n=2), TAC and sirolimus (n=1), and MMF with sirolimus (n=1). Therapy for pre-existing IBD included maintenance of 5-aminosalicylic (5-ASA) (n=3), escalation to vedolizumab (VD) (n=2), and discontinuation of IBD therapy (5-ASA and azathioprine) (n=3). De novo IBD consistent with UC (15 years post-OHT) was managed with 5-ASA (n=1). Six patients (including de novo IBD case) maintained clinical and endoscopic remission of IBD with no flares post-OHT while 2 patients (1 UC and 1 CD) with active disease flares responded clinically and endoscopically to VD escalation from 5-ASA and azathioprine. Among two UC patients with ileal J-pouch pre-OHT, 1 developed refractory pouchitis requiring diverting ileostomy (while on TAC and prednisone) with no pouchitis in the other (maintained on TAC and MMF). Good graft tolerance limited to mild acute cellular rejection episodes was noted in 6 patients, while multiple or no rejection episodes were noted in the remaining two. None of the patients developed CMV or MMF-induced colitis. One patient died due to progressive functional decline unrelated to graft failure or IBD. DISCUSSION The clinical course and treatment of IBD preceding OHT or de novo (though rare) is not significantly worsened or altered post-OHT. The majority of patients achieve clinical and endoscopic remission while on heart transplant-related immunosuppression. Biologic therapy escalation to VD resulted in clinical remission with no effect on graft tolerance. Table 1 Clinical outcomes of OHT patients with concomitant IBD

EPIDEMIOLOGY OF INFLAMMATORY BOWEL DISEASE AMONG EARLY-INDUSTRIALIZED REGIONS OF THE WORLD: CHALLENGES IN SUSTAINABLE HEALTHCARE DELIVERY

Abstract BACKGROUND Early-industrialized regions (e.g., North America, Europe, Oceania) are currently in stage 3 of the epidemiologic evolution of inflammatory bowel disease (IBD), compounding prevalence wherein incidence stabilizes, but prevalence rises rapidly. This epidemiologic stage predicts the trajectory of healthcare infrastructure needs over the coming decades. AIMS 1. Describe current epidemiologic trends in representative stage 3 regions; 2. discuss ways to provide accessible, equitable, and quality IBD care in a sustainable manner; and 3. strategize future steps to prevent disease. METHODS The Canadian Gastro-Intestinal Epidemiology Consortium (CanGIEC) hosted IBD epidemiologists from representative stage 3 regions: Catalonia, Canada, Denmark, Hungary, Israel, New Zealand, Scotland, and the United States and address the rising burden of IBD. Epidemiologic data were reviewed in context using methodological differences between case ascertainment in each region to help explain heterogeneity (Table 1). Attendees engaged in a round-table consensus meeting, voting on priority needs to sustain IBD healthcare delivery given the trajectory of epidemiologic data. Four groups were formed with attendees of various backgrounds to encompass many perspectives, including epidemiologists, clinicians, IBD nurse practitioners, and patient advocates. RESULTS Table 1 describes IBD incidence and prevalence at the most recent year of historical data for each region. Canadian and Scottish studies included the forecasting of future prevalence estimates, a method that allows for proactive decision-making to accommodate the increasing number of individuals living with IBD. In 2028, the forecasted prevalence of IBD in Lothian, Scotland, was 1,023 per 100,000; and in 2030, the forecasted prevalence of IBD in Canada was 981 per 100,000. Table 2 describes the topics brought up in response to the aims, and the level of priority. Limited resources for a growing IBD population are a major cause for concern, negatively impacting access to and quality of care. To optimize quality of care, a multidisciplinary team approach is necessary. Suggestions for support in managing mild IBD cases include virtual care and remote monitoring, nurse-driven clinics, and cooperation with primary care physicians; this would help free-up in-person appointments with specialists for moderate-to-severe cases. Interventions that prevent IBD through modifying environmental and behavioral determinates, will have the largest impact on decelerating prevalence rates over time. DISCUSSION Forefront at the meeting was the fact of the continuing rise of IBD prevalence, augmenting the challenges faced by healthcare systems and practitioners. There are plausible and actionable solutions to achieve successful management of IBD upon initiating changes in healthcare policy.

P1110 Collagenous colitis, clinical features, risk factors and treatment outcome: A large case series from the largest teaching Hospital in London, UK

Abstract Background Microscopic colitis is a cause of chronic watery, non-bloody diarrhoea diagnosed mainly on histology after taking biopsy from macroscopically normal colonoscopy. Thereby mainly two subtypes can be identified: Lymphocytic and collagenous colitis. So far, no biomarkers for the diagnosis of microscopic colitis have been identified. Here, we looked at, risk factors and treatment outcome of collagenous colitis in large series of cases. Methods In this study, we analysed all cases of collagenous colitis diagnosed from 2018-2022 in the Northeast London from 5 different teaching hospitals. 104 cases were identified and their electronic health record from hospital and from the primary care physicians (GP) were manually reviewed. Results In this cohort, 24% male, 76% female with ratio of (1:3), with mean age of 65 years. Forty percent were active or ex-smoker. PPI uses were associated with in 81% cases. While NSAIDS and statin were associated in 56% and 49% cases respectively. We also found that SSRI use were noted about 31% cases. Painless watery diarrhoea was the main cause for referral in 90% of cases, while complaint of abdominal pain noted in only 39% cases. Thirty-five (35%) cases noted to have history of weight loss. Forty-eight (48%) patients received treatment with Budesonide, 46% treated with loperamide, 5% with Immunomodulator or Biologics and 1% Bismuth Subsalicylates respectively. Other autoimmune disease were associated in 6% cases and 2% cases were associated with Coeliac disease. in Nineteen (19%) of cases symptoms improved immediately after stopping above associated drugs without any specific therapy. Twenty-five (25%) percent relapses 6 months after stopping of therapy. Patients present with abdominal pain, and arthralgia were significantly (p<0.001) higher risk of relapsing compared to patients with other symptoms. Conclusion In this large series of collagenous colitis, we found that in addition to associated drug use is not only risk, patient presents with abdominal pain and arthralgia have higher risk of relapse, after stopping of therapy of collagenous colitis . Further studies are needed to identify biomarker of this frustrating disease which has significant impact on patients of quality of life.

P1186 Unveiling the reality of Collagenous colitis: Beyond its Benign Façade

Abstract Background Microscopic colitis is a cause of chronic watery, non-bloody diarrhoea diagnosed mainly on histology after taking biopsy from essentially normal colonoscopy. Thereby mainly two subtypes can be identified: Lymphocytic and collagenous colitis. So far, no biomarkers for the diagnosis of microscopic colitis have been identified. Hower, despite being benign nature of this disease .it often trigger Two weeks wait (cancer path way) of the in the UK. Methods In this study, we analysed all cases of collagenous colitis diagnosed from 2018-2022 in the Northeast London from 5 different teaching hospitals. 104 cases were identified and their electronic health record from hospital and from the primary care physicians (GP) were manually reviewed. Results In this cohort, 24% male, 76% female with ratio of (1:3), with mean age of 65 years. Forty percent were active or ex-smoker. Painless watery diarrhoea was the main cause for referral in 90% of cases, 7% had painless bloody diarrhoea, whilst 3% complaint painful bloody diarrhoea. Abdominal pain noted in only 39% cases. Thirty-five (35%) cases noted to have history of weight loss. Among these patients, 27% had Haemoglobin < 130g/L, including 7% had <105g/L. Twenty nine percent had Faecal calprotectin (FCP) > 50 microgram/gm of stool and 14% had FCP >200. Seventeen percent had serum inflammatory marker raised CRP (normal 0-10). Thirteen percent (13%) of these patient trigger two weeks pathway referral as they had positive Faecal immunochemical test (FIT) which used for bowel cancer screening test, Twenty-seven (27%) presents did not require any treatment, got better after stopping suspected medication as a cause, while 73 % require treatment, of whom 5% require treatment with immunomodulator/ Biologics. Conclusion In this large series of collagenous colitis, we found that, despite being benign condition, it can present with alarming features which both health care provider and patient should be aware of, in order to avoid unnecessary anxiety. Further studies are needed to identify biomarker of this condition.

P229 Comparison of Different Histological Scoring Systems for Ulcerative Colitis [Nancy Histological Index, Robarts Histopathology Index and IBD-DCA (Inflammatory Bowel Disease-Distribution, Chronicity, Activity Score)] Among Specialists in GI Pathology and General Pathologists Pre- & Post Workshop

Abstract Background Histopathology is an emerging treatment target and an important parameter in predicting clinical outcomes of patients with ulcerative colitis (UC). Histological scoring indices Nancy Histological Index (NHI) and Robarts Histopathology Index (RHI) have been developed and validated for UC. We aim to compare the inter-observer reliability of NHI, RHI and the recently described Inflammatory Bowel Disease-Distribution, Chronicity, Activity (IBD-DCA) Score among gastrointestinal (GI) pathologists versus general pathologists pre- and post-workshop to determine the scoring system with the best reproducibility. Methods Digital whole slide images of 20 H&E-stained biopsies of ulcerative colitis (UC) cases are scored independently by 6 GI pathologists and 44 general pathologists that attended the Singhealth GI Pathology Course 2023 using NHI, RHI and IBD-DCA on the digital Pathpresenter platform. The 44 course participants performed the scoring before the course and again after attending a 3-hour IBD workshop on the assessment of histological remission using these 3 scoring systems. Data tabulation using “Free Online Surveys” platform is collated and intraclass correlation coefficient (ICC) of each component of the scoring indices is calculated. The ICC values of <0.5, 0.5–0.75, 0.75–0.9, and >0.9, indicate ‘poor’, ‘moderate’, ‘good’, and ‘excellent’ agreement, respectively. Results There is good inter-observer reliability for IBD-DCA ‘Activity’ component (ICC 0.85) and NHI (ICC 0.83) among GI pathologists while lBD-DCA ‘Distribution’ component (ICC 0.395) has the poorest agreement. Poor to moderate inter-observer reliability for all 3 scoring systems (ICC 0.4 – 0.6) is seen among the 44 participants pre-workshop with an observed post-workshop improvement, achieving best agreement for the NHI, ‘lamina propria neutrophils’ component of RHI and IBD-DCA ‘activity’ component (ICC 0.7). Conclusion GI pathologists are generally consistent in assessing disease activity in UC with good inter-observer reliability for NHI (a scoring system with an emphasis on activity grade) and only the ‘activity’ component of the IBD-DCA. Our study confirms NHI as a reliable scoring system for UC with the best reproducibility and favour its application to assess histological response in routine clinical practice to help gastroenterologists better manage patients with UC. We have also demonstrated that improvement in NHI scoring reproducibility can be achieved after training workshop for pathologists less familiar with the application of IBD histological scoring.

P1170 Long-term outcomes of newly diagnosed Inflammatory Bowel Disease (IBD) patients: results from the nationwide EpidemIBD study of GETECCU

Abstract Background Aims: 1) To describe the main epidemiological and clinical characteristics of patients at IBD diagnosis and the long-term outcomes; 2) to analyse the use of drugs for IBD, and the need of hospitalisations and surgeries; 3) to compare IBD management based on the type of disease and the resources of the hospitals. Methods Prospective, population-based nationwide registry. Adult patients diagnosed with IBD, Crohn’s Disease (CD), Ulcerative Colitis (UC) or IBD unclassified, during 2017 in the 17 Spanish regions were included. Patients who consented were followed-up for 5 years (yr) after diagnosis. Treatment was grouped into 5 categories: mesalamine (oral or topical), steroids (intravenous, oral, or topical), immunomodulators (thiopurines, methotrexate or cyclosporine), biologics (anti-TNF, vedolizumab, ustekinumab) or JAK inhibitors (JAKi), and surgery. Hospitals were classified into high resources and low resources ones. Cumulative incidence of exposure to each of the studied treatments was estimated by Kaplan-Meier curves; curves were compared with log-rank test. Results 3,301 incident cases of IBD diagnosed during 2017 in 108 hospitals, covering over 22 million inhabitants in Spain (about 50% of the population), were enrolled into the follow-up study. Main characteristics of the cohort are summarised in table 1. Median diagnosis delayed was 3.5 months (5.6 in CD and 2.7 in UC, p<0.001). During the 5-yr follow-up, 25% of UC patients progressed to more extensive involvement, while 8% of CD patients with inflammatory behaviour progressed to either stricturing or fistulising behaviour. Most of the patients who received mesalamine, corticosteroids, or immunomodulators initiated treatment within the first 2 years after diagnosis (figure 1). However, the cumulative incidence of biologics/JAKi usage steadily increased over time, reaching 49% by the 5-yr timepoint in CD. In terms of surgeries, a progressive increase in cumulative incidence was observed in CD; the incidence of colectomy remained stable in UC from the 2nd year post-diagnosis. A higher cumulative incidence of biologics/JAKi usage, hospitalisations, and surgeries was observed in CD at high resources hospitals; no differences were observed in the use of other therapeutic resources or the management of UC. Conclusion In the EpidemIBD large-scale epidemiological study, we have observed that the delay in diagnosing IBD is shorter than previously described. Approximately 50% of patients with CD and 20% of patients with UC ended up receiving biologics/JAKi in the first 5 yrs following diagnosis. The percentage of patients undergoing surgery was lower than previously reported; in the case of UC, the majority of colectomies occurred within the first 2 yrs after diagnosis.

P1082 A comparative analysis of persistence of advanced therapies among patients with Inflammatory Bowel Disease in Taiwan

Abstract Background The prevalence of inflammatory bowel disease (IBD) has been rapidly increasing in Asia. Advanced therapies have significantly improved outcomes for moderate to severe cases of IBD. With the expanding availability of advanced therapies, the selection of the most suitable treatment option has become crucial. Among various factors, treatment persistence holds paramount importance. We present the first study in Asia that compares real-world persistence rates among advanced therapies in IBD patients in Taiwan. Methods In this retrospective cohort study, we enrolled patients with IBD who were treated with five advanced therapies: infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST), and tofacitinib (TOF) at Linkou Chang Gung Memorial Hospital between October 2017 and April 2023. UST followed a standard maintenance dosing frequency of every 12 weeks, while TOF was permitted for use only as a second-line treatment option for UC in Taiwan. We compared baseline data and drug persistence rates within the first 52 weeks for the overall group, biologic-naïve patients, and biologic-experienced patients. Results A total of 432 IBD patients were included, with 173 (40%) having ulcerative colitis (UC) and 259 (60%) having Crohn's disease (CD). The majority of patients were male, with a mean age of 43.6 years and a mean BMI of 22.6. UST showed the highest rate of dose escalation (22%). Across all five drugs, the primary reason of discontinuation was secondary loss of response, with IFX having the highest discontinuation rate due to side effects (20%). Other baseline characteristics were presented in Table 1. Kaplan-Meier analysis revealed that all biologics exhibited a persistence rate of over 50% within the initial 52 weeks. UST demonstrated the highest 52-week persistence rates in overall (87.88%, p < 0.001, Figure 1a), biologic-naïve (96.55%, p = 0.002, Figure 1b) and biologic-experienced CD patients (80.56%, p=0.043, Figure 1c). Although no statistically significant differences were observed between advanced therapies in overall UC patients and other subgroup analyses (Figure 1d-1f). VDZ showed highest 52-week persistence in overall (69.05%, p=0.078, Figure 1d) and biologic-experienced (60.87%, p=0.751, Figure 1f) UC patients. UST had highest 52-week persistence in biologic-naïve UC patients (100%, p=0.329, Figure 1e). Conclusion In this pioneering real-world comparison of advanced therapies across one year in Asia, UST exhibited superior 52-week persistence rates in CD patients. However, the rate of dose escalation in UST was also the highest among these therapies. The study's limitations include its single-center nature and relatively small sample size.

P434 Incidence of chronic end-stage renal disease in patients with inflammatory bowel disease: a population-based cohort study from the French National Health Insurance Database

Abstract Background Renal disorders are among the extra-intestinal manifestations of inflammatory bowel disease (IBD), and treatments may also lead to renal failure. However, the incidence of end-stage renal disease (ESRD), defined as the need for renal replacement therapy (dialysis and/or renal transplantation(RT)), is poorly known. The primary objective of our study was to assess the incidence of ESRD in IBD patients, and to compare it with the non-IBD population. Methods We conducted a prognostic cohort study based on data from the French National Health Insurance Database(SNDS). Prevalent cases of IBD affiliated to the general health insurance scheme during the period 2011-2020 were identified on the basis of declarations long-term diseases ALD 24 or the presence of 2 hospital stays for IBD with ICD-10 codes or a single stay with reimbursement of specific treatments. Incident cases of ESRD were identified on the basis of a stay with a RT or a period with dialysis sessions for at least 45 days. Crude incidence rates of ESRD were calculated over the period for the IBD and the non-IBD population, with their 95% confidence intervals. Results A total of 280,283 IBD patients were included in the study over the period 2011-2020, 134,567 with ulcerative colitis(UC) and 145,716 with Crohn’s disease(CD). The mean age at study inclusion was 39.8 (± 17.1) years. The M/F sex ratio was 0.9. The mean age at incidence of ESRD in the non-IBD population was 65.0 (±17.0) years, the M/F sex ratio cases was 1.7. Among IBD patients, 534 patients began replacement therapy by dialysis or RT, they were younger than non-IBD patients (60.3(±16.7)years, P<0.001).The mean incidence rate of ESRD over the period was 26.4 per 100,000 person-years (IC95% 23.1-29.6), 480 (89.9%) patients entered ESRD by dialysis, and 54 (10.1%) by preemptive RT. In the non-IBD population the mean rate of ESRD was 15.9 per 100,000 person-years (IC95% 14.8- 17.1; P<0.0001 compared with IBD): 79,606 (94.5%) patients entered ESRD by dialysis, and 4,634 (5.5%) by RT (as compared with IBD,P<0.001). In subgroup analysis, the mean incidence rate of ESRD was 22.8 per 100,000 person-years (IC95% 18.9-26.7) in UC patients and 29.5 (IC95% 25.3-33.6) in CD patients. The rates of preemptive RT were 12.4% in UC patients (87.6% dialysis) and 8.6% in CD patients (91.4% dialysis). Over a median follow-up of 6.8 years, the survival rate after ESRD was 40.8% in ESRD-IBD patients VS 34.2% in ESRD non-IBD patients (P<0.001). Conclusion This study shows that the incidence of ESRD is significantly higher in IBD than in the non-IBD population, confirming the need for regular monitoring of renal function in our patients. The high incidence of RT confirms that access to transplantation is not restricted in this population.

P1188 Epidemiology and direct healthcare costs of patients with Inflammatory Bowel Disease (IBD) in an Asian cohort in the first year following diagnosis

Abstract Background Inflammatory Bowel Disease (IBD) is a chronic condition requiring multi-disciplinary care with significant investigation and treatment burden. Indeed, the global treatment market has exceeded US$ 20 billion and is expected to exceed 27 billion in 2030. We aim to study the epidemiology and direct healthcare costs of newly diagnosed IBD patients in their first year of diagnosis in Singapore General Hospital (SGH) and identify factors associated with high direct healthcare costs. Methods The study included patients identified from a prospectively maintained IBD registry of SGH. We enrolled patients newly diagnosed with IBD from 2015 to 2022. Patients who received prior treatment or investigation at other institutions were excluded. Data on clinical characteristics and direct costs (investigations, medications, clinic visits, hospitalisations and surgeries) were collected. Results A total of 199 patients were enrolled across 2015 - 2022. 96 patients had Ulcerative Colitis (UC) and 103 had Crohn’s disease (CD) (Table 1). There were 26 (20-28) new cases of IBD diagnosed at SGH yearly. Direct healthcare costs of patients in their first year of diagnosis remained steady with an overall 7.1% change in total expenditure from 2015 through 2022. A drop in expenditure happened in 2020 and 2021 due to COVID outbreak and country lockdown. (Fig 1A) The mean cost per patient-year (PPY) was US$12995 for CD US$104345 for UC. 10 (8-11) patients required admission within the first year of diagnosis, with a mean hospitalisation cost PPY of $269717 (± 73771). Overall, inpatient costs accounted for 39.3 % (IQR 34.8 - 44) of yearly expenditure (Fig 1B). A median of 16.7% (14.6-22.1) of patients were started on biologics within the first year of diagnosis. Patients with CD had significantly greater mean expenditure than those with UC on imaging ($1036 vs $328, p = 0.001) and biologics ($1535 vs $603, p = 0.033). Patients above the 75th percentile of mean cost PPY were defined as having high healthcare cost. This was $12265 and $15957 for UC and CD respectively. Factors associated with high costs were hospitalisation (p < 0.001), biologics (p = 0.001), surgery (p = 0.01) for both UC and CD. UC extent, CD behaviour, history of smoking and age> 40 were not predictive of high costs. Conclusion Patients with CD have greater expenditure compared to patients with UC in the first year following diagnosis. Biologics use, surgery and hospitalisation are significant drivers of costs. The proportion of newly diagnosed patients requiring admission and their corresponding costs have remained consistent during our period of study. These findings encourage early identification of at-risk patients with institution of treatment to minimise hospitalisation and surgical burden.

P1120 New-onset Inflammatory Bowel Disease is uncommon in patients with psoriasis, psoriatic arthritis and spondylarthritis treated with secukinumab: a retrospective cohort study in a tertiary centre

Abstract Background Secukinumab (SEC) is an IL-17A inhibitor prescribed in patients with immune mediated inflammatory diseases like psoriasis (PsO), psoriatic arthritis (PsA) and spondylarthritis (SpA). Conflicting data are available on the onset of inflammatory bowel disease (IBD) among patients after the start of SEC. We aimed to provide data evaluating pre-existing and newly diagnosed IBD in patients being treated with SEC. Methods All patients receiving SEC at a single tertiary centre in The Netherlands between 2012-2022 were identified through the pharmacy registry. Data from electronic medical records were retrospectively collected: baseline (i.e. at initiation of SEC) characteristics, medical history (including pre-existing IBD), use of (disease modifying) concurrent medication, clinical symptoms, biochemistry (C-reactive protein, faecal calprotectin), endoscopy with pathology and cross-sectional imaging (CT, MRI, intestinal ultrasound). Patients were excluded if they received ≤3 doses of SEC. Results A total of 351 patients were included with one or more of the following indications for SEC treatment: PsO in 166/351 (47%), PsA in 130/351 (37%), axial SpA in 130/351 (37%), peripheral SpA in 31/351 (9%) and juvenile idiopathic arthritis in 1/351 (0.3%). Frequently used co-medication were NSAIDs (44%), topical corticosteroids (37%) and methotrexate (16%). Median follow-up time was 48 months (IQR 22,74). In total, ten patients with IBD were identified: 5/351 (1.4%) patients had pre-existing IBD (2/5 Crohn’s disease, 3/5 ulcerative colitis) and 5/351 (1.4%) patients developed IBD after SEC initiation (3/5 Crohn’s disease, 1/5 ulcerative colitis, 1/5 IBD-unclassified) (Table 1). All new-onset IBD cases were confirmed with endoscopy and pathology. Predominant clinical symptoms were diarrhoea, abdominal pain and haematochezia. In patients with new-onset IBD median time from initiation of SEC to development of clinical symptoms was 1.3 months (range 0-12) and median time to diagnosis was 7.5 months (range 3-16). Out of patients with pre-existing IBD in remission 2/5 developed clinical symptoms after start of SEC with a median time to development of 9 months (range 6-12); 3/5 patients sustained remission. After starting SEC 25% of patients reported gastrointestinal symptoms, however diagnostic work-up took place in only 52% of these patients revealing no signs of IBD. Conclusion In our cohort new-onset IBD after SEC initiation was uncommon (<2%) with a short median time to onset. IBD seemed equally distributed among indications. Caution and monitoring of gastrointestinal symptoms during SEC treatment is warranted in patients with pre-existing IBD, considering the possibility of an exacerbation.

P1144 Forecasting the Future Prevalence of Inflammatory Bowel Disease in Korea through 2048: An Epidemiologic Study Employing Autoregressive Integrated Moving Average Models

Abstract Background The global escalation of Inflammatory Bowel Disease (IBD) has precipitated an increased burden of disease and economic impact, particularly accentuated within the Asian context. The primary objective of this study is to predict the future prevalence trajectory of IBD in Korea and elucidate the pattern of its evolution. Methods Data from the Korean National Health Insurance Service (2004–2018) were analyzed using a validated diagnostic algorithm to identify IBD patients. An autoregressive integrated moving average (ARIMA) model, employing 2004–2017 data, predicted future trends based on past values and error correction. The model's accuracy was validated against the actual 2018 patient count. We projected IBD patient numbers and prevalence from 2018 to 2048, using a generalized linear model (GLM) to determine influencing factors. Results A consistent annual increase in the number of IBD cases across all age groups was observed from 2004 to 2018, with prevalence peaking in the 20–39 age group. The validation of our prediction model demonstrated an acceptable range of error for IBD prevalence, with a 2.45% error rate and a mean absolute difference of 2.61. The 2018–2048 projections confirm a steady rise in Crohn’s disease (CD), ulcerative colitis (UC), and IBD prevalence across both genders (Figure 1). IBD prevalence is projected to increase from 104.19 per 100,000 in 2018 to 149.59 per 100,000 by 2028, and further to 239.73 per 100,000 by 2048 (95% confidence interval [CI]: 223.73–255.73), marking a 130% increase. By 2048, the prevalence rates for UC and CD were estimated to be 159.40 per 100,000 (95% CI: 137.38–181.42) and 91.11 per 100,000 (95% CI: 0.81–181.41), respectively. The Average Annual Percent Change (AAPC) of IBD is predicted at 4.51%, varying from a 2.77% decrease in those over 60 to a 14.20% increase in the 20–39 age group. Gender-stratified forecasts show a higher AAPC in males (6.17%) compared to females (2.75%) over the next 30 years. The highest AAPC, valued at 19.48, was noted in the male group aged 20–39 years. GLM analysis indicates significant age, gender, and temporal effects on IBD prevalence, with marked gender disparities in specific age groups for both CD and UC. In UC, males aged 20–39 experienced a significantly higher increase in prevalence than females. For CD, males also showed a higher prevalence increase than females in the 20–39 and 40–59 age groups (all interaction p-values < 0.05; Table 1). Conclusion This study forecasts a significant increase in Korean IBD prevalence by 2048, especially among males and the 20–39 age group, highlighting the need to focus on these high-risk demographics in future disease management.

Treatment of Inflammatory Bowel Disease with Biologics in Japan: A Single-Center, Retrospective Pharmacoeconomic Study.

Biologics are essential for treating inflammatory bowel disease (IBD); however, only a few studies have validated cost-effective treatment options and patient factors for biologic use using real-world data from Japanese patients with IBD. Here, we aimed to provide pharmacoeconomic evidence to support clinical decisions for IBD treatment using biologics. We assessed 183 cases (127 patients) of IBD treated with biologics between November 2004 and September 2021. Data on patient background, treatment other than biologics, treatment-related medical costs, and effectiveness index (ratio of the C-reactive protein-negative period to drug survival time) were analyzed using univariate and multivariate logistic regression analyses. Drug survival was determined using Kaplan-Meier survival curve analysis. The outcomes were to validate a novel assessment index and elucidate the following aspects using this index: the effectiveness-cost relationship of long-term biologic use in IBD and cost-effectiveness-associated patient factors. Body mass index ≥25 kg/m2 and duration of hypoalbuminemia during drug survival correlated significantly with the therapeutic effectiveness of biologics. There were no significant differences in surgical, granulocyte apheresis, or adverse-event costs per drug survival time. Biologic costs were significantly higher in the group showing lower effectiveness than in the group showing higher effectiveness. These findings hold major pharmacoeconomic implications for not only improving therapeutic outcomes through the amelioration of low albumin levels and obesity but also potentially reducing healthcare expenditure related to the use of biotherapeutics. To our knowledge, this is the first pharmacoeconomic study based on real-world data from Japanese patients with IBD receiving long-term biologic therapy.

Forecasting the future prevalence of inflammatory bowel disease in Korea through 2048: an epidemiologic study employing autoregressive integrated moving average models.

The global inflammatory bowel disease (IBD) escalation has precipitated an increased disease burden and economic impact, particularly in Asia. This study primarily aimed to predict the future prevalence of IBD in Korea and elucidate its evolution pattern. Using a validated diagnostic algorithm, we analyzed data from the Korean National Health Insurance Service between 2004 and 2017 to identify patients with IBD. We predicted the number and prevalence of patients with IBD from 2018 to 2048 with the autoregressive integrated moving average method. A generalized linear model (GLM) was also employed to identify factors contributing to the observed trend in IBD prevalence. Our prediction model validation demonstrated an acceptable error range for IBD prevalence, with a 2.45% error rate and a mean absolute difference of 2.61. We foresee a sustained average annual increase of 4.51 IBD cases per 100 000, culminating in a prevalence of 239.73 per 100 000 by 2048. The forecasted average annual percent change was 6.17% for males and 2.75% for females over the next 30years. The GLM analysis revealed that age, gender and time significantly impact the prevalence of IBD, with notable disparities observed between genders in specific age groups for both Crohn's disease and ulcerative colitis (all interaction P<0.05). Our study forecasts a notable increase in Korean IBD prevalence by 2048, particularly among males and the 20-39 age group, highlighting the need to focus on these high-risk groups to mitigate the future disease burden.

Topical Clindamycin For Acne Vulgaris: Pharmacovigilance Safety Review and Retrospective Analysis of Gastrointestinal Events

Background: Clindamycin, a lincosamide antibiotic, was the 125th most prescribed medicine in the US in 2020. Topical formulations that combine clindamycin with benzoyl peroxide or a retinoid are commonly used for acne vulgaris (AV) treatment. While oral and topical clindamycin carry warnings/contraindications regarding the development of gastrointestinal (GI) adverse events (AEs), the real-world incidence of these AEs with topical clindamycin is unknown. The objective is to provide an overview of safety data for topical clindamycin when used for AV treatment.&#x0D; Methods: Safety data from published literature on PubMed® (case reports, clinical trials data, retrospective data), previously unpublished worldwide pharmacovigilance data (from January 1, 1900-December 31, 2022), and two unpublished retrospective cohort studies of US electronic medical records (EMR; January 1, 2011 to January 31, 2019) were reviewed, with a focus on inflammatory bowel disease (IBD) and GI AEs following topical clindamycin monotherapy or combination treatment&#x0D; Results: There have been only 4 published case reports of topical clindamycin-associated GI AEs, which were all published between the years 1981-1997. In 8 published pivotal phase 3 clinical trials of topical clindamycin monotherapy or combination treatment for AV, GI-related AEs were reported in 1.4% of clindamycin-treated participants (38/2,672; safety populations). According to the pharmacovigilance data, the rate of GI-related adverse drug reactions with topical clindamycin-containing products was 0.000045% (64/141,084,533). In 1 published retrospective report, there were 0 reports of colitis from the 1,124 patients estimated to have received topical clindamycin prescriptions in the years 1977-1980. In the first retrospective EMR study, results indicate that physicians prescribe topical clindamycin for AV treatment equally to patients with a history of IBD (19.0%; 98/515) or without (20.7%; 14,495/70,151). The second retrospective EMR study showed that among patients with AV and an initial prescription for topical clindamycin (monotherapy or combination; n=18,012), there were 3 (0.02%) incident cases of pseudomembranous colitis within 30 days; none of these cases had a history of IBD.&#x0D; Conclusions: A review of published case reports, clinical trials safety data, worldwide pharmacovigilance data, and retrospective US prescription data demonstrate that GI events—including colitis or pseudomembranous colitis—in patients exposed to topical clindamycin is extremely low, regardless of IBD history.&#x0D; Support: Ortho Dermatologics