Inflammatory Bowel Disease Flare Research Articles

SAGES guidelines for the use of laparoscopy during pregnancy.

When pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD). The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Expert opinion was utilized when the available evidence was deemed insufficient. The expert panel agreed on ten recommendations addressing the management of appendicitis, biliary disease, and IBD during pregnancy. Conditional recommendations were made in favor of appendectomy over nonoperative treatment of appendicitis, laparoscopic appendectomy over open appendectomy, and laparoscopic cholecystectomy over nonoperative treatment of biliary disease and acute cholecystitis specifically. Based on expert opinion, the panel also suggested either operative or nonoperative treatment of biliary diseases other than acute cholecystitis in the third trimester, endoscopic retrograde cholangiopancreatography rather than common bile duct exploration for symptomatic choledocholithiasis, applying the same criteria for emergent surgical intervention in pregnant and non-pregnant IBD patients, utilizing an open rather than minimally invasive approach for pregnant patients requiring emergent surgical treatment of IBD, and managing pregnant patients with active IBD flares in a multidisciplinary fashion at centers with IBD expertise.

A step closer to understanding how a diet high in simple carbohydrates may cause dysbiosis.

The gut microbiota is an integral part of the human metaorganism that is required to shape physiologic host immune responses including host defense against pathogens. Disease-associated gut dysbiosis has been characterized by blooms of pathobionts, which are bacterial species that can drive disease under certain conditions. Pathobionts like Enterobacteriaceae often bloom during flares of inflammatory bowel disease (IBD) and are causally linked with IBD in murine models. In this issue of the JCI, Hecht and colleagues investigated how simple carbohydrates are causally linked to the bloom of the gut pathobiont Klebsiella pneumoniae, which belong to the Enterobacteriaceae family. Notably, the presence of fiber reduced the dissemination of K. pneumoniae into the blood and liver in a colitis model. Their findings provide a diet-related mechanism for gut dysbiosis, which has implications in the management of IBD and other conditions in which gut dysbiosis is an underlying factor.

P021 Uptake, safety, and effectiveness of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide study using data from the Clinical Practice Research Datalink

Abstract Background/Aims The safety and effectiveness of pneumococcal vaccine in people with immune mediated inflammatory diseases (IMIDs) is not known, which may contribute to suboptimal uptake. We investigated UK wide pneumococcal vaccine uptake in adults with IMIDs, the association between pneumococcal vaccination and disease flares, and the effectiveness of pneumococcal vaccine in preventing pneumonia in this at-risk population. Methods Adults with incident rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and spondyloarthritis (SpA) prior to 31st August 2018 in the Clinical Practice Research Datalink (CPRD) Gold were included. The study was approved by CPRD research data governance (Reference 21_000614). We calculated the proportion of patients vaccinated against pneumococcal pneumonia. To investigate the association between vaccination and IMID flare, we employed a self-controlled case series analysis, adjusted for season. The study period was up-to six-month before and six-month after the date of pneumococcal vaccination. This period was partitioned into induction (14 days pre-vaccination) and exposed periods (up-to 90 days post vaccination) with the remaining time considered unexposed. Incidence rate ratios (IRR) and 95% CI were calculated. We conducted a multivariable nested case-control study to assess vaccine effectiveness. Cases were patients hospitalised with pneumonia and were matched to up to ten controls for age and sex. Multivariable conditional logistic regression was used to calculate odds ratio (OR) and 95% CI. Results We included 32,277 IMID patients: 14,151 with RA, 13,631 with IBD, 3,804 with SpA and 691 with SLE. Overall uptake of pneumococcal vaccination was 50% (95% CI 49.4% -50.5%). Vaccination uptake was significantly lower in the under 45-year-olds, in patients with IBD and in those without additional indication for vaccination at 29.7%, 38.4%, 42.7% respectively. In the safety study, data for 1001, 854, 424 vaccinated patients with primary care consultations for joint pain, AIRD flare, and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with AIRD flare (IRR (95% CI) 1.07 (0.93-1.22)), primary care consultations for joint pain (IRR (95% CI) 0.95 (0.83-1.10)), and IBD flare (IRR (95% CI) 0.82 (0.64-1.06)) in the 90-days post vaccination. The vaccine effectiveness study included 25,707 patients, either with (n = 2,771) or without (n = 22,936) a hospitalisation record for pneumonia after IMID diagnosis. Patients hospitalised for pneumonia compared with their matched controls, had higher odds of current smoking, deprivation, corticosteroid prescriptions, additional indication for vaccination, primary care consultations, hospital admissions and prescriptions. In the multivariable adjusted model, pneumococcal vaccination was associated with reduced odds of hospitalisation for pneumonia (OR (95% CI) 0.88 (0.78-0.98). Conclusion The uptake of pneumococcal vaccine is low in IMID patients. Pneumococcal vaccination is not associated with IMID flare and is protective against pneumonia. These findings call for promotion of pneumococcal vaccination in IMID by health professionals. Disclosure G. Nakafero: None. M.J. Grainge: None. C.D. Mallen: Grants/research support; NIHR, MRC, Versus Arthritis and BMS. T. Card: None. J.S. Nguyen Van-Tam: Consultancies; CSL Seqirus and Moderna. Royalties; AstraZeneca and Sanofi Pasteur. A. Abhishek: Consultancies; NGM Bio, Limbic and Inflazome.. Royalties; UpToDate, Springer, Cadilla Pharmaceuticals.. Grants/research support; AstraZeneca and Oxford Immunotech..

Not Your Typical Ulcerative Colitis Patient

Background: Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD. Despite the huge therapeutic progress of the last decade, one must not forget about the side effects that currently available medications might have and the challenges to both patient and physician. Case presentation: We present the case of a 33-year-old woman, that initially was admitted for diffuse abdominal pain, nausea and bloating. After careful investigation she was diagnosed with a drug induced acute pancreatitis, caused by sulfamethoxazole/trimethoprim taken for UTI. Further investigations established a diagnosis of ulcerative colitis. Initial treatment with mesalamine resulted in another acute pancreatitis event that required hospitalization. An anti-TNF therapy with infliximab was started with initial clinical remission but then she developed another adverse reaction, this time paradoxical psoriasis, while having an IBD flare. So, this begged the question, how do we treat a patient that had an adverse reaction to every prior treatment? Conclusion: Developing newer and newer therapies will bring also different possible adverse events that should be carefully diagnosed and managed.

The Effect of an Electronic Medical Record-Based Clinical Decision Support System on Adherence to Clinical Protocols in Inflammatory Bowel Disease Care: Interrupted Time Series Study.

Clinical decision support systems (CDSSs) embedded in electronic medical records (EMRs), also called electronic health records, have the potential to improve the adoption of clinical guidelines. The University of Alberta Inflammatory Bowel Disease (IBD) Group developed a CDSS for patients with IBD who might be experiencing disease flare and deployed it within a clinical information system in 2 continuous time periods. This study aims to evaluate the impact of the IBD CDSS on the adherence of health care providers (ie, physicians and nurses) to institutionally agreed clinical management protocols. A 2-period interrupted time series (ITS) design, comparing adherence to a clinical flare management protocol during outpatient visits before and after the CDSS implementation, was used. Each interruption was initiated with user training and a memo with instructions for use. A group of 7 physicians, 1 nurse practitioner, and 4 nurses were invited to use the CDSS. In total, 31,726 flare encounters were extracted from the clinical information system database, and 9217 of them were manually screened for inclusion. Each data point in the ITS analysis corresponded to 1 month of individual patient encounters, with a total of 18 months of data (9 before and 9 after interruption) for each period. The study was designed in accordance with the Statement on Reporting of Evaluation Studies in Health Informatics (STARE-HI) guidelines for health informatics evaluations. Following manual screening, 623 flare encounters were confirmed and designated for ITS analysis. The CDSS was activated in 198 of 623 encounters, most commonly in cases where the primary visit reason was a suspected IBD flare. In Implementation Period 1, before-and-after analysis demonstrates an increase in documentation of clinical scores from 3.5% to 24.1% (P<.001), with a statistically significant level change in ITS analysis (P=.03). In Implementation Period 2, the before-and-after analysis showed further increases in the ordering of acute disease flare lab tests (47.6% to 65.8%; P<.001), including the biomarker fecal calprotectin (27.9% to 37.3%; P=.03) and stool culture testing (54.6% to 66.9%; P=.005); the latter is a test used to distinguish a flare from an infectious disease. There were no significant slope or level changes in ITS analyses in Implementation Period 2. The overall provider adoption rate was moderate at approximately 25%, with greater adoption by nurse providers (used in 30.5% of flare encounters) compared to physicians (used in 6.7% of flare encounters). This is one of the first studies to investigate the implementation of a CDSS for IBD, designed with a leading EMR software (Epic Systems), providing initial evidence of an improvement over routine care. Several areas for future research were identified, notably the effect of CDSSs on outcomes and how to design a CDSS with greater utility for physicians. CDSSs for IBD should also be evaluated on a larger scale; this can be facilitated by regional and national centralized EMR systems.

Hyperbaric Oxygen Enabled a Transition to Oral Steroids in an Acute Severe Ulcerative Colitis Flare.

Ulcerative colitis (UC) is characterized in part by a dysregulated response to tissue hypoxia. While intravenous (IV) steroids are the mainstay of treatment for acute severe UC (ASUC), up to one-third of patients are refractory to steroids alone and require rescue therapy. A 71-year-old female with extensive UC on infliximab presented with abdominal pain and more than 10 bloody bowel movements per day. Her infliximab concentration was undetectable with a positive antibody level. Flexible sigmoidoscopy on hospital day (HD)1 showed Mayo 3 colitis; biopsies for CMV were negative. She was started on hydrocortisone IV with improvement in her CRP from 56 to 40mg/L. She also received 1 dose of vedolizumab. Hyperbaric treatments were offered but declined. By HD5, she was clinically improved, with a CRP of 9mg/L. She was transitioned from IV to oral steroids. After starting oral steroids her symptoms relapsed, her CRP increased from 9 to 48mg/L, and IV steroids were reinitiated on HD6. Hyperbaric medicine was reconsulted and she completed 5 hyperbaric oxygen (HBO2) treatments (HD 7-11) with prompt reduction in CRP, stool frequency, and bleeding. After 3 HBO2 treatments, she transitioned successfully from IV to oral steroids on HD9. This case demonstrates the potential of HBO2 therapy to help UC patients transition successfully from IV to oral steroids who were previously refractory to de-escalation. HBO2 therapy may be considered as an adjunctive treatment for patients with ASUC to potentiate the effects of standard therapies and avoid progression to colectomy.

Impact of COVID-19 Treatment on Real-World Outcomes in Inflammatory Bowel Disease.

While there are multiple safe and effective agents for COVID-19 treatment, their impact in inflammatory bowel disease (IBD) remains uncertain. Our objective was to assess the effects of these therapies on both IBD and COVID outcomes. A single-center retrospective study of adult patients with IBD who contracted COVID-19 between 12/2020 and 11/2022 was performed. Patients were stratified by COVID-19 treatment (antivirals and/or intravenous antibodies) vs no therapy. The primary outcome was the development of severe COVID-19 infection, defined by need for supplemental oxygen, corticosteroids and/or antibiotics, or hospitalization. Secondary outcomes included rates of withholding advanced IBD therapy (defined as biologic agents or small molecules) and of post-COVID-19 IBD flare. Of 127 patients with COVID-19 infection, 70% were on advanced therapies, 35% received COVID-19 treatment, and 15% developed severe COVID-19. Those treated for COVID-19 were more likely to be on corticosteroids [odds ratio (OR) 4.61, 95% confidence interval (CI) 1.72-12.39, p = 0.002] or advanced IBD therapies (OR 2.78, 95% CI 1.04-7.43, p = 0.041). After adjusting for age, race, sex, corticosteroid use, obesity, COVID-19 vaccination status, and severe COVID-19 infection, those treated for COVID-19 were more likely to have IBD therapy held (OR 6.95, 95% CI 1.72-28.15, p = 0.007). There was no significant difference in rates of post-COVID-19 IBD flares or severe COVID-19 infection. There were no COVID-related deaths. Patients with IBD on advanced therapies were frequently treated for acute COVID-19. Although COVID-19 treatment was associated with temporary withholding of IBD therapy, it did not result in increased IBD flares.

Acute Severe Ulcerative Colitis Flare Complicated by Myopericarditis and Infliximab-Induced Hepatitis.

In acute inflammatory bowel disease (IBD) flare presentation with tachycardia and chest pain, an underlying myocardial injury should be investigated.Mucosal healing should be evaluated endoscopically in cases of partial response to biologics.Both cytomegalovirus (CMV) infection and infliximab-induced liver injury may lead to acute hepatitis.

Safety of Secukinumab from 1Million Patient-Years of Exposure: Experience from Post-Marketing Setting and Clinical Trials.

Secukinumab is an anti-interleukin (IL)-17A monoclonal antibody indicated for multiple immunological disorders. Here, we aim to summarize secukinumab safety in clinical trials (CTs) and post-marketing setting (PMS) until 25June2022. Adverse events (AEs) were summarized with crude reporting rate (RR) per 100 patient-years (PY) in PMS for all reported indications and with exposure-adjusted incident rates (EAIR) per 100 PY in pooled 47 CTs for approved indications. Secukinumab exposure totaled 1,159,260 PY in PMS and 27,765 PY in CTs. AEs were mostly (> 80%) non-serious in PMS. EAIR for serious AEs was 7.0/100 PY. Nasopharyngitis (RR 0.59/100 PY, EAIR 16.08/100 PY) and pneumonia (RR 0.14/100 PY, EAIR 0.17/100 PY) were the most common infection and serious infection, respectively. Candida infections (RR 0.20/100 PY, EAIR 2.16/100 PY) were the most common fungal infections. Inflammatory bowel disease (IBD) was observed in PMS (0.14/100 PY) and CTs (0.26/100 PY). Most (76%) patients with prior IBD did not report IBD flare during CTs. PMS monitoring identified paradoxical skin reactions including dyshidrotic eczema (RR 0.006/100 PY) and pyoderma gangrenosum (RR 0.003/100 PY). Secukinumab safety profile with increased patient exposure remained favorable. Paradoxical skin reactions were identified in post-marketing monitoring.

A232 TEMPORAL TRENDS IN RE-HOSPITALIZATION RATES AMONG PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN THE POST-BIOLOGIC ERA

Abstract Background Hospitalization for severe inflammatory bowel disease (IBD) flares or complications are a major source of morbidity and healthcare expenditure. Aims To assess temporal trends in 30-day and 90-day re-hospitalization rates among persons with Crohn’s disease (CD) and ulcerative colitis (UC) in the post-biologic era. Methods We conducted a population-based study of all non-elective IBD-related hospitalizations among patients with CD and UC in Ontario, Canada between April 1, 2002 and March 31, 2020. We identified individuals, admissions, and variables of interest from Ontario population health administrative datasets housed at IC/ES. We performed multivariable logistic regression analysis to evaluate the association between time period of hospitalization (2002-2007 vs. 2002-2007 vs. 2007-2012 for CD; 2004-2008 vs. 2008-2012 vs. 2012-2016 vs. 2016-2020 for UC) and rates of 30-day and 90-day re-hospitalization, adjusting for patient age, sex, co-morbidities, residential setting, income quintile, hospital type of initial admission, and clustering of hospital admissions within patients. We excluded patients with elective admissions or length of stay ampersand:003C24 hours, and those without continuous valid Ontario health care registration during the 90-day period following hospital discharge. Results There were 18,625 hospitalizations among 14,868 patients with CD, and 10,830 hospitalizations among 9,264 patients with UC. The 30-day re-hospitalization rate was 8.5% for patients with CD and 9.7% for patients with UC, while the respective 90-day re-hospitalization rates were 15.0% and 13.8%. For CD, re-admission rates differed across the 3 time periods (pampersand:003C0.0001 for 30-day and p=0.012 for 90-day). For UC, re-hospitalization rates differed across the 4 time periods for 30-day re-hospitalization (p=0.048), but not 90-day (p=0.080). There was a higher relative odds of CD-related re-hospitalization in 2002-2007 as compared to 2012-2017 (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.16-1.50 for 30-day; aOR 1.14, 95% CI [1.03-1.26] for 90-day). For UC, there was a higher relative odds of re-hospitalization in 2012-2016 as compared to 2016-2020 (aOR 1.26, 95% CI [1.05-1.52] for 30-day; aOR 1.22, 95% CI [1.04-1.43] for 90-day). Conclusions Up to 15% of patients with IBD in Ontario are re-admitted to hospital within 90 days of hospital discharge. The risk of re-hospitalization may have decreased over time in the post-biologic era. Our findings could be explained by changing access to inpatient and/or outpatient resources, improvements to medical and/or surgical care, shifting patient behaviour with respect to healthcare resource utilization, or residual confounding. These results require validation in other jurisdictions. Funding Agencies None

A256 NAVIGATING IBD CARE : HEALTHCARE PROVIDERS’ INSIGHTS ON IMPLEMENTATION OF NURSE NAVIGATOR-LED IBD FLARE PATHWAY

Abstract Background Disparities in access to healthcare for persons living with inflammatory bowel disease (IBD) persist. An IBD nurse navigational role promises to improve access to evidence-based specialist care by minimizing inequities in access to care. Little is known about how to implement a provincial nurse navigational role in the Canadian health system. Aims This study aims to explore healthcare providers' perceptions of barriers and facilitators to the implementation of an evidence-based IBD flare pathway through a provincial nurse navigational role. Methods This was a national qualitative study performed in collaboration with the CCC PACE Program, in which two virtual semi-structured group interviews were conducted in 2022. One group interview was with six IBD nurses from three provinces, and the second was with five gastroenterologists from five provinces. Participants were purposefully recruited. The Consolidated Framework for Implementation Research (CFIR) and the Capability, Opportunity, Motivation, and Behaviour (COM-B) frameworks informed the interview script development. Data were transcribed verbatim and subjected to content analysis, with major themes categorized into the COM-B domains. The results of preliminary data analysis are presented. Results While IBD nurses emphasized the critical role of effective communication tools, standardized referral systems, strong administrative support and patient education and engagement as facilitators, they also highlighted challenges like patient resistance, variability of training and the necessity for tailored patient care. Other barriers identified were the medical complexity of managing overlapping conditions, remote vs in-person considerations and the perception and definition of a flare. On the other hand, IBD-focused gastroenterologists emphasized the potential of integrating pathways into electronic medical records and the value of empowering nurse navigators. However, they pointed out concerns regarding the inherent variability in disease presentation, entrenched medical beliefs, comfort levels with nurse-led pathways and the inherent diversity in medical practices. Both groups identified resource constraints as a barrier and an effective triage process as a facilitator. Conclusions This study sheds light on the multifaceted perceptions of healthcare providers concerning the implementation of an evidence-based IBD flare pathway through a provincial nurse navigational role. These insights underline the complexity of implementing a nurse navigational role and the need for targeted interventions and resources to address the identified barriers while leveraging the facilitators. Funding Agencies CCC

Antibiotics for inflammatory bowel disease: Current status.

There is abundant literature reporting about the use of antibiotics in inflammatory bowel disease (IBD), but their role in the management of IBD is not entirely clear. Diverse infectious organisms have been implicated in the pathogenesis of Crohn's disease. Also, infections are believed to be a trigger for flares of ulcerative colitis. The benefit of the routine use of antibiotics in IBD is equivocal. However, there are certain situations, where antibiotics have a clear role and evidence of benefit: perianal fistula, intra-abdominalabscesses in Crohn's disease, acute pouchitis and infection-related flares. However, there is a lack of supportive evidence for the routine use of antibiotics in all disease-related flares. Evidence indicates a lack of benefit of intravenous antibiotics in acute severe ulcerative colitis and only limited benefit in active ulcerative colitis. Limited evidence suggests the role of a combination of oral antibiotics in pediatric ulcerative colitis. Certain targeted antibiotic regimens have been used in IBD. In ulcerative colitis, limited evidence suggests the benefit of the use of an antibiotic cocktail directed against Fusobacterium varium. Therapy directed against Escherichia coli does not seem to have a benefit in inflammatory Crohn's disease. In Crohn's disease, antimycobacterial therapy may result in symptomatic improvement but no durable benefit. Antitubercular therapy (ATT), on the contrary, may result in fibrotic transformation, suggesting a need to avoid misdiagnosis and limit the duration of ATT in Crohn's disease. This review assesses the published literature with respect to antibiotic use and provides guidance to clinicians in appropriate antibiotic use in various situations in the setting of IBD.

MULTIPLE BIOSIMILAR INFLIXIMAB SWITCHING IS NOT ASSOCIATED WITH DISEASE FLARE IN INFLAMMATORY BOWEL DISEASE: A REAL-WORLD EFFECTIVENESS ANALYSES IN A NATIONAL U.S. COHORT

Abstract BACKGROUND Infliximab (IFX) biosimilars are available for inflammatory bowel disease (IBD). Many options of IFX biosimilars exist, however there is a paucity of data on the safety and efficacy of switching between multiple IFX biosimilars. The goal of this study is to evaluate the safety and outcomes in patients who received multiple IFX biosimilars in a National U.S. Cohort of patients with IBD. METHODS We conducted a retrospective cohort study of IBD patients who received maintenance IFX originator from 2017- 2019 in the national Veterans Affairs (VA) healthcare system. Crohn’s disease (CD) and ulcerative colitis (UC) patients were identified using a previously validated algorithm. All cases, exposures and outcomes were confirmed by chart review. Patents on IFX originator were identified by dispensed medication from the VA Corporate Data Warehouse. Patients were classified as no-switch (NS)- receiving originator but no biosimilar during study period, Single Switch (SS)- switch from IFX originator to one biosimilar, or Double Switch (DS)- switch from IFX originator to two different biosimilars. Primary outcome was IBD flare, defined as escalation of steroid, IBD-related Emergency department visit or hospitalization within 12 months. Secondary outcomes were immunogenicity, serious infection, and infusion reaction. Event rates of the DS group were compared to NS and SS groups using univariate and multivariate logistic regression models adjusting for patient and non-patient factors. RESULTS A total of 789 patients (487 CD, 298 UC, 4 IBDU) on maintenance IFX originator were identified during the study period. Of these, 410 patients were categorized as NS, 249 as SS, and 130 as DS. Overall, the rate of flare within 12 months was 19.9% (22.2% NS, 15.3% SS, 21.5% DS, p= 0.08), rate of infection was 11.2% (11.5% NS, 8% SS, 16.2% DS, p= 0.056). No statistically significant differences in rates of immunogenicity or infusion reaction were identified between the DS and NS or SS groups. In multivariate (MV) logistic regression including age, race, gender, concomitant medication, comorbidity, and VA priority status, no significant differences in flares at 12 months was observed between the DS (ref) and NS (aOR 1.12, 95% CI 0.68-1.84), or SS groups (aOR 0.64, 95% CI 0.36-1.12). In MV analyses, SS was associated with lower rate of infection compared to DS (aOR 0.41, 95% CI 0.21-0.82). CONCLUSION In a national U.S. cohort of patients with IBD, multiple IFX biosimilar switching was not associated with flare at 12 months compared to patients continued on IFX originator or with a single IFX biosimilar switch. However, double switch was associated with increased odds of infection compared to single switch. These findings provide reassurance that multiple IFX biosimilar switching for IBD is effective but further study on infection risks may be warranted.

REAL-WORLD SAFETY AND EFFICACY OF USTEKINUMAB AND VEDOLIZUMAB IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract CONTEXT/PURPOSE Ustekinumab and vedolizumab are approved biologicals to treat adults with inflammatory bowel disease (IBD) but currently administered off-label for children. Aims: (1) assess safety and adverse events during treatment with ustekinumab or vedolizumab in pediatric IBD and (2) assess steroid free clinical remission and mucosal healing at 6 months and 1 year. METHODS Retrospective chart review of pediatric patients (&amp;lt;22 years) with IBD treated at an academic hospital and two affiliated practices. Inclusion: Patients with IBD who received either ustekinumab or vedolizumab between January 2015 to June 2022 with minimum of 6 months follow up. Clinical remission assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI) &amp;lt; 10 and short Pediatric Crohn’s Disease Activity Index (shPCDAI) &amp;lt;15, and mucosal healing by fecal calprotectin &amp;lt;250 mcg/gram. RESULTS Fifty-eight patients received vedolizumab and 55 patients received ustekinumab. Patients with ulcerative colitis (UC) or IBD unclassified (IBDU) on vedolizumab were more likely to be in remission at 6 months (58% vs. 42%, p = 0.3, Table 1) and significantly higher at achieving 1-year steroid free remission (64% vs. 27%, p = 0.019) compared to ustekinumab. Over two thirds of biologic naïve and about half of biologic exposed patients who received vedolizumab achieved 1-year steroid free remission (78% vs. 58%, Figure 1). All patients who received ustekinumab were biologic exposed. In Crohn’s disease (CD), no significant difference was seen in children receiving vedolizumab compared to ustekinumab at 6 months remission (57% vs. 63%, p = 0.7) or 1-year steroid free remission (70% vs. 70%, p &amp;gt;0.9). All biologic naïve patients and half of biologic exposed patients who received vedolizumab achieved 1 year steroid free remission. Both bionaive and two thirds of biologic exposed patients who received ustekinumab achieved 1-year steroid free remission (100% vs. 67%). When comparing vedolizumab and ustekinumab, no significant difference was observed in 6 month remission (73% vs. 59%, p = 0.2) and 1-year steroid free remission based on calprotectin (61% vs. 66%, p = 0.7). Similar to clinical remission rates, biologic naïve patients tended to have higher remission rates based on calprotectin. Five patients each had minor adverse events with ustekinumab and vedolizumab, and 20 were hospitalized mostly for IBD flare. CONCLUSION Both biologicals were safe and effective in achieving clinical remission at 6 months and 1 year. They were more effective when used in bionaive patients, although numbers were very low for ustekinumab. The superior efficacy of vedolizumab in UC and IBDU at 1-year may be attributed to larger cohort of bionaive patients. Larger multicenter prospective studies are needed to validate these findings regarding efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. Table 1 Remission on Vedolizumab and Ustekinumab Figure 1 Remission on Vedolizumab vs. Ustekinumab Stratified by Biologic Exposure

BIOLOGICS AND SMALL MOLECULES USED IN IBD MIMICS: HIGHLIGHTING THE IMPORTANCE OF DIAGNOSIS CONFIRMATION

Abstract INTRODUCTION Since 2009, inflammatory bowel disease (IBD) specialists have been utilizing “IBD Live,” a weekly live video conference with a global audience of 150-200 participants, to discuss the multidisciplinary management of their commonly seen and most challenging cases. While most cases presented were confirmed as IBD, a substantial number were mimics for which IBD was not the ultimate diagnosis. We previously categorized all IBD Live cases and identified the frequency of “IBD mimics.” Here, we examine the use of biologic medications for these cases which ultimately were determined to be something other than IBD. METHODS Cases have been recorded and archived since May 2018. 371 total cases from May 2018 through February 2023 were reviewed spanning 186 hours. 65 of those cases were determined to be IBD mimics, defined as those with features of IBD that ultimately resulted in a non-IBD diagnosis. IBD mimics were analysed and categorized in terms of their biologic usage. RESULTS 25 of the 65 mimics (38.5%) were treated with biologics for presumed IBD. 14 were treated with one biologic, 5 with two biologics, and 6 with three or more biologics. The biologics used in the management of these IBD mimics included infliximab (n=21), vedolizumab (n=12), adalimumab (n=11), ustekinumab (n=6), and certolizumab (n=1). Of the 25 cases of biologic usage without definitive confirmation of IBD, 6 ended up with a diagnosis where biologics were an appropriate treatment for the mimic. These mimics included drug-induced colitis (n=3), Behcet’s disease (n=1), segmental colitis associated with diverticulosis (SCAD; n=1), and CTLA-4 haploinsufficiency with autoimmune infiltrates (CHAI; n=1). Several of the IBD mimics were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialled on tofacitinib (for Sweet’s syndrome, PIK3cd, and SCAD). There were 3 patients with confirmed IBD, in remission on a biologic, who subsequently had symptoms concerning for an IBD flare. In each of these cases, IBD was not the cause of their symptoms (e.g., cecal volvulus). There were 4 patients with confirmed IBD, in remission off biologics, who later developed symptoms suspicious for an IBD flare. Each of these cases was trialled on biologics to treat the supposed flare; however, symptoms were ultimately found to be due to an IBD mimic (e.g., eosinophilic esophagitis). 33 of the 65 IBD mimics were never treated with biologics. DISCUSSION In a 5-year period at IBD Live, 17.5% of cases (65 of 371) were found to be IBD mimics. 38.5% (25 of 65) of these were treated with biologics. The diverse presentation of signs and symptoms of IBD and IBD mimics requires reassessment of the biologic therapy in patients without response. Often the biologic needs to be optimized for IBD, but in some cases, the diagnosis of IBD will need to be called into question. Table 1 IBD mimics and biologics used Abbreviations BADAS = bowel-associated dermatosis-arthritis syndrome, BCL = B-cell lymphoma, CD = Crohn’s Disease, CHAI = CTLA-4 haploinsufficiency with autoimmune infiltrates, C-MUSE = cryptogenic multifocal ulcerous stenosing enteritis, CMV = cytomegalovirus, CVID = common variable immunodeficiency, EGPA = eosinophilic granulomatosis with polyangiitis, GABA = gamma-aminobutyric acid, IBD = inflammatory bowel disease, IMHMV = idiopathic myointimal hyperplasia of the mesenteric veins, PIK3cd = phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunit delta, PNH = paroxysmal nocturnal hemoglobinuria, SCAD = segmental colitis associated with diverticulosis, STI = sexually transmitted infection, UC = Ulcerative Colitis. Image 1: Biologic usage in IBD mimics

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

P555 Switching from intravenous vedolizumab to subcutaneous maintains clinical remission even in intensified patients with Inflammatory Bowel Disease. One year follow-up

Abstract Background Vedolizumab is a humanized monoclonal antibody. It is indicated for moderate to severe flare of Inflammatory Bowel Disease (IBD). Subcutaneous (SC) vedolizumab, is a major advantage for patients for home administration. This study aimed to analyze the percentage of clinical and biochemical remission at 52 weeks in all IBD patients on treatment with intravenous (IV) vedolizumab after switching to the SC one. Methods Single-center, descriptive, observational, and retrospective study. The study included all the IBD patients (19 patients) who were at the moment of inclusion with IV vedolizumab treatment in a tertiary hospital, who underwent a switch from IV vedolizumab to SC vedolizumab. In addition, the relationship between treatment with intensified IV vedolizumab and subsequent drug levels versus patients without intensification for 52 weeks. Results Ten patients (22.6%) were diagnosed with Ulcerative Colitis (UC) and 9 patients (47.3%) with Crohn´s disease (CD). The baseline characteristics of the 19 patients are described in Table 1. Reasons for starting IV vedolizumab: there was loss of response to a first anti-TNF in 10 patients (52.6%) and loss of response to two previous anti-TNFs was observed in 3 patients (15.7%). In 4 patients (21%) IV vedolizumab was started as the first line of treatment due to the increased risk of infections and a previous history of neoplasia. Finally, in 2 patients with CD (10.5%) it was started as prevention of recurrence. Up to a total of 8 patients (42.1%) were on an intensified IV vedolizumab before switching to SC vedolizumab. All 19 patients (100%) were in clinical remission and 15 patients (78.9 %) remained in biochemical remission prior to switching to SC vedolizumab. At the end of the follow-up (52 weeks) all of them achieved clinical remission and 17 patients (89.4%) achieved biochemical remission (Figure 1). Therefore, biochemical remission was achieved in 10% more patients after the switch. It was noted that biochemical remission was achieved in 87% of patients on the intensified regimen with IV vedolizumab versus 100% of patients on the non-intensified regimen. No statistically significant differences were obtained between patients who had been on intensified IV vedolizumab and those who had not. At one year of follow-up, SC vedolizumab was suspended in one patient due to muscle pain, and IV vedolizumab was restarted again. Conclusion Following the standard dose switch of SC vedolizumab, clinical remission is maintained, achieving biochemical remission in 89.4 % of patients one year with SC vedolizumab with maintained vedolizumab levels, even in previously intensified IV vedolizumab patients.

P1105 Short-term exposure to environmental air pollution and inflammatory bowel disease flares: a time-stratified case cross-over study

Abstract Background Some epidemiological studies suggest that long-term exposure to environmental air pollutants, such as particulate matter (PM), could have a role in inflammatory bowel disease (IBD) incidence and pathogenesis. However, less is known about the potential effect of short-term air pollution exposure. The aim of this study is to investigate whether short-term exposure to environmental air pollution is associated with the occurrence of IBD flares. Methods Anonymized hospital discharge records (HDR) with ICD-9-CM codes 555 (Crohn’s disease) and 556 (ulcerative colitis) for years 2002-2009 from all hospitals of the Lombardy region were collected. All HDR of adult patients (18-75 years) resident in Milan were included, except for recurrent hospitalizations within 6 months. Each record was assigned daily PM ≤10 µm (PM10) concentrations at municipality level by averaging PM10 levels of the day of admission with the levels of the day before (lag01) and of each preceding day up to six days before (lag06). To evaluate the association between PM10 and IBD-related hospitalizations, a time-stratified case-crossover study design was applied. Conditional logistic regression models, calculating Odds Ratios (OR) and 95% Confidence Intervals (95%CI) per increments of 10 µg/m3 of PM10, were performed. Results Overall, 2,176 hospital admissions (males=1,137, Crohn’s disease=1,264, ulcerative colitis=912) were included. In the entire population no clear association between PM10 and IBD-related hospitalization was identified, notwithstanding a small risk increase for males (OR: 1.03; 95%CI: 0.99-1.08 at lag04). When further stratifying for ICD code, an increased risk of hospitalization for "left-sided ulcerative colitis" (ICD code: 556.5) was found in males only, for exposures in all days preceding hospitalization up to lag04 (1.28; 1.05-1.28; 59 cases, 207 controls) (Figure 1). In females, the association was weaker, although positive (1.14; 0.91-1.42; 49 cases, 164 controls). No relevant findings emerged when looking at other ICD codes. Conclusion We observed an increased risk of IBD-related hospitalization in male patients with left-sided ulcerative colitis per increasing levels of air pollution in the days preceding hospital admission. Although preliminary, our findings suggest the possible role of sex as an effect modifier of the influence that air pollution might exert on IBD flares. Further studies are needed to better comprehend the complex framework characterizing the interplay between environmental and individual factors contributing to IBD.

P370 Quality of life in inflammatory bowel diseases – is the flare all that matters?

Abstract Background Burden in inflammatory bowel diseases (IBD) is high and affects both physical and psychological status. Short inflammatory bowel disease questionnaire (SIBDQ) is a self-administered health-related quality of life questionnaire that evaluates social, bowel, emotional and systemic dimension. Our aim is to evaluate the impact of IBD status on patients’ daily life. Methods We analysed 82 patients diagnosed with Crohn’s disease or ulcerative colitis or that were admitted between March 2021 and April 2022 in Fundeni Clinical Institute, Bucharest. SIBDQ consists of ten questions, with score ranging from 10 (poor) to 70 (optimal). Patients completed SIBDQ and we assessed disease status and determined biological and clinical markers. Results 51% of patients were diagnosed with Crohn’s Disease. 79% were in clinical remission. The mean age was 39.53±12.9 years old and 52.4% were men. Mean illness duration was 8.03±7.18 years. Mean SIBDQ score was 50.25±14.51, with significantly higher scores in the remission subgroup (55.26±10.30 vs. 31.11±12.24, p&amp;lt;0.001) and it correlated with faecal calprotectin level (ρ=-0,502) and C-reactive protein level (ρ=- 0,531), without regard to disease type or sex. There were no correlations between SIBDQ score and Crohn’s disease or ulcerative colitis phenotype, duration since diagnosis, presence of extraintestinal manifestations or history of abdominal surgery related to IBD. Conclusion Patients with IBD flares have low quality of life and SIBDQ scores correlate with markers of disease severity, comparable to previously-published literature. Patients in clinical remission presented with higher SIBDQ scores, independently of IBD phenotype or previous surgery. Acute flares of IBD have a major impact on daily life, additional psychological and social support is needed in order to improve management.

P708 Multiple Biosimilar Infliximab Switching is Not Associated with Adverse Outcomes in Inflammatory Bowel Disease: A Real-World Effectiveness Analysis in a National U.S. Cohort

Abstract Background Infliximab (IFX) biosimilars are available for inflammatory bowel disease (IBD). Many options of IFX biosimilars exist, however there is a paucity of data on the safety and efficacy of switching between multiple IFX biosimilars. The goal of this study is to evaluate the safety and outcomes in patients who received multiple IFX biosimilars in a National U.S. Cohort of patients with IBD. Methods We conducted a retrospective cohort study of IBD patients on maintenance IFX originator from 2017- 2019 in the national Veterans Affairs (VA) healthcare system. Crohn’s disease (CD) and ulcerative colitis (UC) patients were identified using a previously validated algorithm. Cases, exposures and outcomes were confirmed by chart review. Patents on IFX originator were identified by dispensed medication from the VA Corporate Data Warehouse. Patients were classified as no-switch (NS)- receiving originator but no biosimilar during study period, Single Switch (SS)- switch from originator to one biosimilar, or Double Switch (DS)-switch from IFX originator to two different biosimilars. Primary outcome was IBD flare, defined as escalation of steroid, IBD-related Emergency department visit or hospitalization within 12 months. Secondary outcomes were immunogenicity, serious infection, and infusion reaction. Event rates of the DS group were compared to NS and SS groups using univariate and multivariate (MV) logistic regression models adjusting for patient and non-patient factors. Results 789 patients (487 CD, 298 UC) on maintenance IFX originator were identified. Of these, 410 patients were categorized as NS, 249 as SS, and 130 as DS. Overall, the rate of flare within 12 months was 19.9% (22.2% NS, 15.3% SS, 21.5% DS, p= 0.08), rate of infection was 11.2% (11.5% NS, 8% SS, 16.2% DS, p= 0.056). No statistically significant differences in rates of immunogenicity or infusion reaction were identified between the DS and NS or SS groups. In MV logistic regression including age, race, gender, medication, comorbidity and VA priority status, no significant differences in flares at 12 months was observed between DS (ref) and NS (aOR 1.12, 95% CI 0.68-1.84), or SS groups (aOR 0.64, 95% CI 0.36-1.12). In MV analyses, SS was associated with lower rate of infection compared to DS (aOR 0.41, 95% CI 0.21-0.82). Conclusion In a national U.S. cohort of patients with IBD, multiple IFX biosimilar switching was not associated with flare at 12 months compared to patients continued on IFX originator or with a single IFX biosimilar switch. However, DS was associated with increased odds of infection compared to single switch. These findings provide reassurance that multiple IFX biosimilar switching for IBD is effective but further study on infection risks may be warranted.