Disease Course Of Inflammatory Bowel Disease Research Articles

The circadian rhythm as therapeutic target in inflammatory bowel disease

Abstract The primary objectives of the management of patients with inflammatory bowel disease (IBD) are to prevent IBD flares, prevent/delay disease progression and improve patients’ quality of life. To this end, one needs to identify risk factor(s) associated with flare-ups and disease progression. We posit that disruption of circadian rhythms is one of the key factors that is associated with risk of flare-up and disease progression. This hypothesis is based on published studies that show: (1) The circadian rhythm regulates many biological processes including multiple IBD-relevant biological processes that are critical in inflammatory/immune processes such as environment/microbe interaction, microbe/host interaction, intestinal barrier integrity and mucosal immunity—all central in the pathogenesis of IBD, and (2) Circadian machinery is the primary tool for the host to interact with the environment. Circadian misalignment results in a loss of preparedness of the host to respond and adjust to the environmental changes that could make the host more vulnerable to IBD flare-ups. In this review, we first provide an overview of circadian rhythms and its role in healthy and disease states. Then we present data to support our hypothesis that: (1) IBD patients have disrupted circadian rhythms (“social jet lag”) and (2) circadian misalignment and associated disrupted sleep decreases the resiliency of IBD patients resulting in microbiota dysbiosis, more disrupted intestinal barrier integrity and a more aggressive disease phenotype. We also show that circadian-directed interventions have a potential to mitigate the deleterious impact of disrupted circadian and improve IBD disease course.

Faecal biomarkers for diagnosis and prediction of disease course in treatment-naïve patients with IBD.

Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). This studyprovides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.

Probiotics for Inflammatory Bowel Disease; A Deep Dive into their Impact on Disease Course and Associated Health Risks.

To date, the underlying pathology of inflammatory bowel disease (IBD) is undetermined. Disturbance of intestinal gut microbiota was implicated in many health diseases, including IBD. Increasing evidence suggests that probiotics play a beneficial role in restoring the balance of the gut ecosystem. This review searched multiple databases for relevant works that examined probiotics' possible benefits in adults with IBD. Probiotic mode of action in ulcerative colitis patients and Crohn's disease were examined with respect to probiotic strain, their benefits, and their advantages in adult cases. Eligible studies for inclusion were assessed and analyzed. They were effective in reducing IBD disease course, inducing and maintaining remission, particularly for ulcerative colitis patients, with good efficacy and safety profile. However, the evidence for Crohn's disease was lacking. Probiotics positively affect IBD-related risks, reducing the risk of gastrointestinal malignancy and optimizing treating them. Additionally, they improved reduced fertility odds for both genders. The osteoporosis risk among IBD patients was also reduced, although the duration of use and dose were still not established. There was an encouraging role for them in reducing IBD -cardiovascular risks among cases with acute myocardial infarction and those with chronic heart failure. Finally, they had novel use in reducing IBD-related depression and improved overall mental health. In conclusion, we recommend probiotics as an adjuvant therapeutic option for IBD therapy for ulcerative colitis; however, their role in Crohn's disease needs further research.

P1179 Long-term impact of COVID-19 on the disease course of IBD: a meta-analysis

Abstract Background Viral infections have been implicated in the exacerbation of immune-mediated inflammatory diseases like inflammatory bowel disease (IBD). The COVID-19 pandemic, therefore, sparked interest in whether infection with the virus has an adverse effect on the course of IBD. Since the existing evidence is conflicting and limited by a small sample size, we performed the very first meta-analysis to study the long-term impact of SARS-CoV-2 infection on the disease course of IBD. Methods We performed a systematic literature search in MEDLINE and EMBASE for studies that explored the risk of adverse IBD outcomes following a SARS-CoV-2 infection. We used the random effects model meta-analysis to calculate the pooled hazard ratio for the risk of IBD flares following the acute phase of COVID-19. Subgroup meta-analysis was carried out for the risk of the outcomes by IBD subtype. Meta-regression was carried out for sex and duration of follow-up. The ROBINS-E tool for observational studies was used to assess the quality of the studies. Results A total of 5 studies were included in the meta-analysis. The studies were based on cohorts from Denmark, Italy, the US, and a cohort from a consortium of the EU comprising a total of 34977 SARS-CoV-2 positive IBD patients and 53270 IBD patients without the infection as controls. Two of the studies had a high risk of bias according to the quality assessment tool. The meta-analysis did not show an increased risk of IBD-related outcomes in IBD patients who contracted a SARS-CoV-2 infection compared to those who did not (HR: 1.0514, CI: 0.7547- 1.4646, p= 0.7671). There was substantial heterogeneity between the included studies (91%, p&amp;lt;0.01). There was no significant difference between CD and UC patients in terms of disease flare (CD- HR: 0.9134, CI: 0.8163-1.0220; UC- HR: 0.8257, CI: 0.7549-0.9032). Neither sex nor the duration of follow-up was a predictor of the overall effect size. Conclusion In this group of patients, SARS-CoV-2 infection does not increase the risk of adverse outcomes related to IBD. High-quality studies with longer follow-up duration are required to understand the long-term impact of SARS-CoV-2 infection on IBD prognosis.

P1174 The disease course of elderly patients with Inflammatory Bowel Disease two years prior to their death

Abstract Background The number of elderly patients with inflammatory bowel disease (IBD) is increasing. Hence, more patients will be dying with their IBD. Limited research has examined the disease course of IBD in the aging body, particularly in the period preceding their death. The purpose of this study was to investigate the disease course of elderly IBD patients leading up to the end of their lives. Methods This was a nationwide population-based study using the national Danish registries. We used a validated algorithm to identify patients that were diagnosed with Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) in a period between 1976-2018 from the Danish National Patient Registry. This information was linked with other national Danish registers which provided data on dates of death, cancer, hospitalisations, and corticosteroid usage. We included 6,183 IBD patients aged 65 and above at death, with no cancer or palliative treatment at the time of death. We analysed IBD-related hospitalisations, corticosteroid usage, and disease relapses (defined as a combined endpoint of corticosteroid prescription and/or hospitalisation, or both), in the two-year period before death. Results We analysed CD, UC and IBDU patients separately, and observed a noticeable spike in hospitalisations, prescription rates of corticosteroids and disease relapses in the last two months before the IBD patients’ death. Out of 6,183 IBD patients, 954 (15.43%) were hospitalised in the last two years before their death (see Table 1 for key characteristics). In the last two months, hospitalisation rates were 139 (28.66%) for CD patients, 155 (23.96%) for UC patients and 83 (34.87%) for IBDU patients. Corticosteroids were prescribed to 1,054 (17.05%) out of 6,183 IBD patients, and in the last two months 90 (20.45%) CD patients, 149 (20.13%) UC patients, and 67 (19.36%) IBDU patients received a corticosteroid treatment. Overall, 1,652 (26.72%) IBD patients experienced a disease relapse two years preceding their death, and during the last two months, 553 (22.45%) CD patients, 194 (24.01%) UC patients and 228 (20.25%) IBDU patients experienced relapses. Conclusion During the two-year period prior to death, we observed that hospitalisation, prescription, and relapse rates were highest during the final two months of life. For better understanding of the disease course of elderly IBD patients, further research should investigate the cause of death and differences between early- and late disease-onset patients as well as establish a cohort for comparison.

Disease Flares Following COVID-19 Vaccination in Patients with Inflammatory Bowel Disease.

Objective Flares of inflammatory bowel disease (IBD) can occur infrequently after vaccination for coronavirus disease 2019 (COVID-19), although the details of this phenomenon are poorly understood. To clarify the possibility of an unfavorable response in patients with IBD, we investigated IBD-related symptoms during the COVID-19 vaccination. Methods Between October 2021 and February 2022, we obtained the COVID-19 vaccination status of 411 IBD patients who were being treated at our institution. The disease course of IBD after vaccination was investigated in 188 patients with ulcerative colitis (UC) and 119 patients with Crohn's disease (CD) who had received at least one dose of the vaccine during the clinical remission phase. The baseline characteristics before vaccination were compared between the patients with UC with or without disease flares. Results During the 30-day follow-up period, eight patients with UC (4.3%) and one patient with CD (0.8%) experienced disease flares following vaccination. Disease flares occurred after the first vaccination in six patients and after the second vaccination in three patients. As for the timing of onset of disease flares, eight events (88.9%) occurred within one week of vaccination. Two patients required hospitalization, and one patient with CD required surgery for an intra-abdominal abscess. The baseline characteristics did not significantly differ between patients with UC who experienced flares and those who did not. Conclusion IBD flares following COVID-19 vaccination are rare and vaccination should therefore be recommended for patients with IBD. However, the possibility of disease flares should be considered for approximately one week after each vaccination, especially in patients with UC.

The Optimal Management of Inflammatory Bowel Disease in Patients with Cancer.

Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern about the impact of IBD therapy on cancer risk and survival, as well as the effects of cancer therapies on the disease course of IBD. Managing IBD in patients with current or previous cancer is challenging since clinical guidelines are based mainly on expert consensus. Evidence is rare and mainly available from registries or observational studies. In contrast, excluding patients with previous/or active cancer from clinical trials and short-term follow-up can lead to an underestimation of the cancer or cancer recurrence risk of approved medications. The present narrative review aims to summarize the current evidence and provide practical guidance on the management of IBD patients with cancer.

P306 Serum tryptophan metabolites as a biomarker for disease severity in patients with IBD

Abstract Background The levels of tryptophan (TRP) metabolites such as kynurenine (KYN), kynurenic acid (KYNA), quinaldic acid, 3-hydrocynynene, anthranilic acid, picolinic acid (PA) and xanthurenic were determined systematically in inflammatory bowel disease (IBD). Previous studies found a negative correlation with TRP levels and IBD disease activity. However, there is no data about serum levels of TRP metabolites and their correlation with severity of IBD. We aimed to determine the correlation between the levels of TRP, its metabolites and the clinical, laboratory, and endoscopic findings of the disease activation including fecal calprotectin. Methods A total of 115 patients, 77 (66.4%) with UC and 38 (33.6%) with CD, were included. Forty three % (n=49) of the patients were female. 57 % (n=66) were male. The mean age of females and males were 42.07±13.39 and 44.23± 10.04 years, respectively. Patients were categorized according to their disease activity: Sixty-five (57%) of the patients were in remission and 50 (43%) were active. The predictive value of the disease activity was evaluated by the levels of serum tryptophan, its metabolites and the fecal calprotectin levels. Results At a cut-off value of ≤11328.41 ng/ml of tryptophan, the sensitivity to predict disease activation is 76.9% and the specificity is 71.7%. On the other hand, at a cut-off value of ≥89.60 µg/g of fecal calprotectin, the sensitivity of detecting disease activation was 88.1% and the specificity was 80.0%. Calprotectin, sedimentation, CRP, KYN/TRP values were found to be significantly higher in patients in the active period than in patients in remission (p&amp;lt;0.001, p&amp;lt;0.001, p&amp;lt;0.007 respectively). KYNA, TRP, and PA values were found to be statistically significantly lower in patients in the active phase compared to those in remission (p=0.01, p&amp;lt;0.001, p=0.022 respectively). Conclusion Serum TRP levels were lower in increased disease activity. Quinolinic acid levels did not differ between active patients and patients in remission. Quinolinic acid, which is the metabolite of TRP degradation, was increased with active disease. However, fecal calprotectin still had superior predictive value for IBD disease activity. Further studies are needed to assess the TRP pathway for the disease severity and disease course in IBD.

S1063 Corticosteroid Use in Inflammatory Bowel Disease (IBD) Patients May Lead to Worse IBD-Related Outcomes After COVID-19 Infection

Introduction: There is growing but limited data on the effects COVID-19 has on the disease course of IBD. COVID-19 can enter epithelial cells of the gut via ACE receptors causing cell dysfunction, inflammation, and dysbiosis. Thus, we set out to evaluate IBD outcomes during and three months after COVID-19 infection. Methods: We performed a retrospective case series comparing IBD patients in remission versus not in remission diagnosed with COVID-19 seen in a single tertiary care center from March 2020 to March 2021. COVID-19 diagnosis was made by positive rapid antigen and/or PCR. We analyzed demographics, medications, need for hospitalization, changes to immunosuppressive therapy, and IBD severity and remission status noted by endoscopic scoring or Physician Global Assessment at the time of COVID-19 diagnosis and 3 months post infection. Results: We identified 57 IBD patients, 30 in remission and 27 not in remission, diagnosed with COVID-19. Comparison of baseline characteristics and COVID-19 and IBD related outcomes are noted in Table. Patients not in remission were more likely to be on steroids, including prednisone and budesonide, and biologics (0% vs 40.7%, p=0.00001; 73.3% vs 96.3%, p=0.03). Patients not in remission were significantly more likely to need escalation in treatment (OR 15.08; CI 2.98-76.3, p=0.001) and had more IBD related hospitalization and surgery at 3 months compared to patients in remission (18.5% vs 0%, p=0.02). We then excluded patients who had changes in IBD medications 90 days prior to COVID-19 diagnosis and found there was still an increased risk for treatment escalation (OR 7, CI 1.27-38.58, p=0.0254). Additionally, patients not in remission on steroids had an increased risk of escalation of IBD related medications, hospitalization, and surgeries than patients not in remission who were not on steroids (OR 12, CI 1.76-81.7, p=0.0111). Conclusion: Our study suggests COVID-19 likely has minimal impact on the clinical course of IBD patients in remission. It remains unclear what the effects are on those not in remission, especially those on corticosteroids. Corticosteroid use is associated with impaired immune response and may lead to dysbiosis by downregulation of protective mucin gene expression as shown in animal models. Thus, infection with COVID-19 in patients on steroids may contribute to an increased risk of dysbiosis and subsequent disease flare. Further study is warranted to study the effects of steroids on IBD related outcomes in patient with COVID-19 infection. Table 1. - Comparison of IBD related outcomes in patients in remission versus those with active disease at time of COVID-19 diagnosis and 3 months afterwards Remission (SD)N = 30 Not in remission (SD)N = 27 P-value Demographics Age 40.2 (16.3) 35.3 (13.7) 0.25 Sex Male 46.7% 33.3% 0.42 Female 53.3% 66.7% 0.42 Race White 70% 74% 0.78 Black 20% 18.5% 1.00 Asian 10% 3.7% 0.61 Hispanic 0% 3.7% 0.47 BMI 26.2 (5.6) 24.8 (4.0) 0.36 Comorbidities Organ transplant 3.3% 7.4% 0.60 Cardiovascular disease 13.3% 11.1% 1.00 Diabetes 3.3% 3.7% 1.00 Chronic lung disease 0% 3.7% 0.47 HTN 10% 7.4% 1.00 Current malignancy 3.3% 0% 1.00 CKD 3.3% 7.4% 0.60 Tobacco use 3.3% 3.7% 1.00 Chronic liver disease 20% 14.8% 0.73 IBD Characteristics Crohn's disease 73.3% 63.0% 0.57 Ulcerative colitis 26.7% 37% 0.57 Activity Mild Moderate Severe 14.8%77.8%7.4% IBD medication use None 6.7% 0% 0.49 5-ASA 23.3% 14.8% 0.51 Immunomodulator 6MP/AZA 3.3% 11.1% 0.34 MTX 10% 7.4% 1.00 Corticosteroids 0% 40.7% 0.00001 Budesonide 0% 18.5% 0.02 Prednisone 0% 22.2% 0.01 Biologics 73.3% 96.3% 0.03 Vedolizumab 16.7% 22.2% 0.74 Anti-TNF 43.3% 51.9% 0.60 Ustekinumab 13.3% 22.2% 0.49 Tofacitinib 0% 0% 1.00 COVID-19 Outcomes Hospitalization 13.3% 7.4% 0.67 ICU with intubation 0% 0% 1.00 Any COVID-19 therapy 3.3% 14.8% 0.18 Death 0% 0% 1.00 IBD medications held 13.3% 29.6% 0.13 IBD Outcomes at 3 months Experienced IBD flare 10% 51.8% 0.005 Escalation of immunosuppression 10% 44.4% 0.00319 Initiation of new steroid therapy 6.7% 22.2% 0.19 IBD related hospitalization/surgery 0% 18.5% 0.02

Dietary Patterns and Gut Microbiota Changes in Inflammatory Bowel Disease: Current Insights and Future Challenges.

Inflammatory bowel disease (IBD) is a result of a complex interplay between genes, host immune response, gut microbiota, and environmental factors. As one of the crucial environmental factors, diet plays a pivotal role in the modulation of gut microbiota community and the development of IBD. In this review, we present an overview of dietary patterns involved in the pathogenesis and management of IBD, and analyze the associated gut microbial alterations. A Westernized diet rich in protein, fats and refined carbohydrates tends to cause dysbiosis and promote IBD progression. Some dietary patterns have been found effective in obtaining IBD clinical remission, including Crohn’s Disease Exclusion Diet (CDED), Mediterranean diet (MD), Anti-Inflammatory Diet (AID), the low-“Fermentable Oligo-, Di-, Mono-saccharides and Polyols” (FODMAP) diet, Specific Carbohydrate Diet (SCD), and plant-based diet, etc. Overall, many researchers have reported the role of diet in regulating gut microbiota and the IBD disease course. However, more prospective studies are required to achieve consistent and solid conclusions in the future. This review provides some recommendations for studies exploring novel and potential dietary strategies that prevent IBD.

Occurrence and Clinical Impact of Eosinophilic Esophagitis in a Large Cohort of Children With Inflammatory Bowel Disease.

Scarce data have investigated the association between pediatric inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and the possible peculiar phenotype and natural history of such an association. Case-control study is based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a combined diagnosis of IBD and EoE were included. The overall prevalence and incidence in 2 periods, 2009 to 2015, and 2016 to 2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups. Eleven patients (age 11.2 ± 2.8 years, Males 91%) with EoE-IBD out of 3090 patients with IBD were identified, resulting in an overall prevalence of 0.35% and an incidence of 0.18% for 2009 to 2015 and 0.45% for 2016 to 2021. Treatment escalation rates for IBD were significantly higher in patients with IBD compared with EoE-IBD at 12- and 24-month follow-up (0% vs 30%, P = .04; and 9% vs 45.5%, P = .03, respectively). Furthermore, patients with IBD were at a significantly higher risk of hospitalization than both EoE-IBD and EoE patients (log rank P < .001). We found no significant differences in major outcomes related to the EoE course in EoE-IBD patients compared with EoE ones. The incidence and prevalence of EoE in children with IBD are low, although the incidence seems to be rising in recent years. Having EoE appears to be associated with a milder IBD disease course, whereas having IBD does not seem to affect the natural history of EoE. More data are needed to better define the phenotype of such association.

P630 Systematic review and meta-analysis: Diagnostic delay and the subsequent impact on the disease course of adult Inflammatory Bowel Disease

Abstract Background Diagnosis of inflammatory Bowel disease (IBD) can be challenging and time consuming. There is substantial variation in the reported time to diagnosis and the impact of diagnostic delay on disease course. We therefore conducted a systematic review to evaluate the length of time to diagnosis and a meta-analysis of the impact of delay on the disease course of IBD. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and final papers were assessed for risk of bias. We searched MEDLINE and Embase for retrospective and prospective studies, published up to December 2020, that reported diagnostic interval, from the time of symptom onset or first consultation to a confirmed diagnosis of IBD, in adults (age ≥18 years). We extracted data from published studies and calculated the weighted median and interquartile range (IQR) of the reported diagnosis interval. Delay was defined as a time period greater than the 75th centile. From eligible studies, we extracted risk estimates and, using random-effects meta-analysis, calculated the pooled odds ratios (OR) and 95% confidence intervals (CI) of studies that examined the association of diagnostic delay with subsequent clinical outcomes, including disease phenotype and surgical intervention. Statistical heterogeneity was assessed, I2 &amp;gt;50% indicating substantial heterogeneity. Results Of 1,533 studies identified, 28 fulfilled the eligibility criteria, including 25,764 patients diagnosed with IBD: Crohn’s disease (CD) = 13,206 and ulcerative colitis (UC) = 12,558. In CD, the pooled weighted median for the diagnostic interval was 8.8 months (IQR 3.0–61.1 months). In UC, the pooled weighted median was 15.2 months (IQR 2.4–62.8). Considering studies from high income countries alone, the pooled weighted median was 6.4 months (IQR 1.7–46.7) in CD, and 2.5 months (IQR 0.3–23.0) in UC. 11 studies were eligible for inclusion in the meta-analysis, representing 6,403 patients diagnosed with IBD (CD; n = 4,902 and UC; n = 1,501). In CD, pooled analysis showed an association between delayed diagnosis and stricturing disease (OR:1.77, CI 1.28–2.46; I2 =61%), penetrating disease (OR: 1.48, CI 1.21–1.82; I2=0%) and intestinal surgery (OR:1.88, CI 1.45–2.44; I2 =34%; figure 1a). In UC, delayed diagnosis was associated with an increased risk of colectomy (OR:4.13, CI 1.04–16.40; I2 =0%; figure 1b). Conclusion Measures are required to reduce delay in the diagnosis of IBD, which is associated with an increase in stricturing and penetrating disease phenotype in CD and a substantially increased risk of surgery in both CD and UC.

P635 Incidence, prevalence, disease phenotype and maximal therapeutic step in Ulcerative Colitis patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem County cohort

Abstract Background Recent trends indicate a change in the epidemiology of inflammatory bowel disease (IBD) with previously low incidence areas now reporting progressive rise. The number of epidemiological population-based studies are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to analyze the incidence and disease phenotype at diagnosis, and the maximal therapeutic step distributions during follow-up in a prospective population-based database from Veszprem Province, including incident ulcerative colitis (UC) patients diagnosed between January 1, 2007 and December 31, 2018. Methods Data of 467 incident UC patients were analyzed (male/female:236/231; median age at diagnosis:36 years(y)[IQR: 25–54]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The source of age- and gender-specific demographic data for statistical analysis was derived from the results of a national population census in 2011. Results Adjusted mean incidence rate was 11.02(CI95%:10.1–12.1)/105 person-years in this 12 year period[males:11.53(CI95%:10.2–13.1)/105; females:10.54(CI95%:9.3–12.0)/105]. Prevalence rate was 283.51(CI95%:265.7–300.7)/105 persons in 2011 and 317.79(CI95%:298.8–335.8) in 2015. For detailed annual incidence rates and age-specific mean incidence rates see Figure 1 and 2. Peak onset age in UC was 20–29 years of age. Diagnostic delay from symptom onset was ≥1year in 19.1%, and ≥3 years in 4.1% of the patients. Disease extension was proctitis(E1) in 22.3%, left sided colitis(E2) in 43.9%, and extensive colitis(E3) in 33.8% of the patients at diagnosis. Patients with extensive colitis were younger(32.9y,SD:16.6) at diagnosis compared to patients with proctitis(40.1y,SD:15.9;p&amp;lt;0.001) or left sided colitis(44.0y;SD:19.1;p&amp;lt;0.001). Extraintestinal manifestations were as follows: hepatic5.4%(PSC 2.1%), arthritis10.7%, ocular0.9%, skin3.6%. Active smokers at diagnosis were 12.6%. Distribution of maximal therapeutic steps during the course of follow-up (8.34y,SD: 3.5) were 5-ASA in 46.9%, systemic corticosteroids in 16.3%, immunosuppressive therapy in 19.3%; anti-TNF biologic therapy in 12.2% and other biologic therapy in 4.3%. Conclusion The incidence of UC in this 12 year period was high, comparable to high-incidence areas in Western European countries, and comparable to previous data from the Veszprem cohort, while prevalence rates continue to rise compared to our previous data.(Lakatos 2011, IBD). Disease extension at diagnosis and distribution of highest treatment step was comparable to European population-based data.(Burisch 2019, JCC).

P671 Occurrence and clinical impact of eosinophilic esophagitis in a large cohort of children with Inflammatory Bowel Disease

Abstract Background Scarce data have investigated the association between pediatric Inflammatory bowel disease (IBD) and Eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and a possible peculiar phenotype and natural history of such association. Methods Case-control study based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a concomitant diagnosis of IBD and EoE were included. Overall prevalence and incidence in 2 periods, 2009–2015 and 2016–2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups. Results Eleven patient (age 11,27 ± 2,83, Male 91%) with EoE-IBD out of 3090 patients with IBD only were identified, resulting in a prevalence of 0,35% and an incidence of 0,18% for the period 2009–2015 and 0,45% for the period 2016–2021. Treatment escalation rates were significantly higher in patients with IBD compared to EoE-IBD at 12 and 24-month follow-up (0 vs 30%, p = 0.04 and 9% Vs 45,5%, p = 0.03, respectively). Patients with IBD only were at a significantly higher risk of hospitalization than both EoE-IBD and EoE only patients (Log Rank p &amp;lt; 0.001). We found no significant differences in major outcomes related to the EoE course in EoE-IBD patients compared to EoE patients. Conclusion Overall, the incidence and prevalence of EoE in children with IBD are low, although the incidence seems to be rising in the six years. Having an EoE appears to be associated with a milder IBD disease course while having an IBD doesn’t seem to affect the natural history of EoE. More data are needed to better define the phenotype of such condition.

COVID-19 is not associated with worse long-term inflammatory bowel disease outcomes: a multicenter case-control study.

Inflammatory bowel disease (IBD) is not associated with worse coronavirus disease 2019 (COVID-19) outcomes. However, data are lacking regarding the long-term impact of severe acute respiratory syndrome coronavirus 2 infection on the disease course of IBD. We aimed to investigate the effect of COVID-19 on long-term outcomes of IBD. We performed a multicenter case-control study of patients with IBD and COVID-19 between February 2020 and December 2020. Cases and controls were individuals with IBD with presence or absence, respectively, of COVID-19-related symptoms and confirmatory testing. The primary composite outcome was IBD-related hospitalization or surgery. We identified 251 cases [ulcerative colitis (n = 111, 45%), Crohn's disease (n = 139, 55%)] and 251 controls, with a median follow-up of 394 days. The primary composite outcome of IBD-related hospitalization or surgery occurred in 29 (12%) cases versus 38 (15%) controls (p = 0.24) and on multivariate Cox regression, COVID-19 was not associated with increased risk of adverse IBD outcomes [adjusted hazard ratio (aHR): 0.84, 95% confidence interval [CI]: 0.44-1.42]. When stratified by infection severity, severe COVID-19 was associated with a numerically increased risk of adverse IBD outcomes (aHR: 2.43, 95% CI: 1.00-5.86), whereas mild-to-moderate COVID-19 was not (aHR: 0.68, 95% CI: 0.38-1.23). In this case-control study, COVID-19 did not have a long-term impact on the disease course of IBD. However, severe COVID-19 was numerically associated with worse IBD outcomes, underscoring the continued importance of risk mitigation and prevention strategies for patients with IBD during the ongoing COVID-19 pandemic.

Impact of SARS-CoV-2 Vaccination on Inflammatory Bowel Disease Activity and Development of Vaccine-Related Adverse Events: Results From PREVENT-COVID.

BackgroundSevere acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course.MethodsWe evaluated coronavirus disease 2019 (COVID-19) vaccine–related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes.ResultsA total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P < .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age <50 years, female sex, vaccine type, and antitumor necrosis factor and vedolizumab use were associated with severe systemic reactions to dose 2. Overall rates (2%) of IBD flare were low following vaccination.ConclusionsOur findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.

GLP-1 based therapies and disease course of inflammatory bowel disease.

BackgroundThe disease course of inflammatory bowel disease (IBD) following treatment with glucagon-like peptide (GLP)-1 based therapies is unclear. The aim of this study was to examine the disease course of IBD in patients treated with GLP-1 based therapies compared with treatment with other antidiabetics.MethodsUsing nationwide Danish registries, we identified patients with IBD and type 2 diabetes who received antidiabetic treatment between 1 January 2007 and 31 March 2019. The primary outcome was a composite of the need for oral corticosteroids, tumour necrosis factor-α inhibitors, IBD-related hospitalisation, or IBD-related surgery. In the setting of a new-user active comparator design, we used Poisson regression to estimate incidence rate ratios (IRR) comparing treatment with GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors with other antidiabetic therapies. The analyses were adjusted for age, sex, calendar year, IBD severity, and metformin use.FindingsWe identified 3751 patients with a diagnosis of IBD and type 2 diabetes and with a prescription of an antidiabetic drug (GLP-1 receptor agonists/DPP-4 inhibitors: 982 patients; other antidiabetic treatment: 2769 patients). The adjusted IRR of the composite outcome was 0·52 (95% CI: 0·42–0·65) for patients exposed to GLP-1 receptor agonists/DPP-4 inhibitors compared with patients exposed to other antidiabetics.InterpretationIn patients with IBD and type 2 diabetes, we observed a lower risk of adverse clinical events amongst patients treated with GLP-1 based therapies compared with treatment with other antidiabetics. These findings suggest that treatment with GLP-1 based therapies may improve the disease course of IBD.

Type D personality is associated with depressive symptoms and clinical activity in inflammatory bowel disease.

Inflammatory bowel disease (IBD) can be exacerbated by stress and depression. Type D personality, characterised by high negative affectivity and social inhibition, represents a vulnerability towards stressors and is associated with adverse outcomes in coronary heart disease. To assess the prevalence of Type D personality in IBD patients and investigate potential associations with disease course. We tested for associations between Type D (Type D Scale-14), depressive symptoms (Hospital Anxiety and Depression Scale's depression subscore ≥11) and recurrent IBD amongst Swiss IBD cohort patients. We built regression models for cross-sectional and Cox proportional hazards models for time-to-event analyses. IBD disease course was assessed by the future occurrence of active disease (Crohn's Disease Activity Index ≥150/Modified Truelove & Witts activity index ≥10) and several IBD-relevant endpoints. Amongst 2275 patients (1005 ulcerative colitis, 1270 Crohn's disease), 672 (29.5%) had Type D. Type D was a significant risk factor for future active disease (adjusted hazard ratio, aHR: 1.60, corrected P value, q=0.007) and predicted the future presence of depressive symptoms (aHR: 3.30, P<0.001). The combination of Type D and depressive symptoms further increased the risk for active disease (aHR: 3.98, q<0.001). However, Type D associated depressive symptoms seemed to be the main contributor to this effect as Type D's predictive power decreased considerably in models corrected for depressive symptoms (aHR: 1.32, CI: 0.97-1.79, q=0.292). Type D personality's prevalence amongst IBD patients was comparable with its prevalence in the general population. Type D was strongly associated with depressive symptoms and showed modest independent associations with IBD prognosis.

IBD-related Malignancies Observed in 2015–2019 : 4 Years’ Results from the Prospective, Nationwide Hungarian Registry IBD-related Malignancies – Hungarian Registry

Introduction: Patients with inflammatory bowel disease (IBD) have an increased risk to develop malignant neoplasms. Neither the exact mechanism, nor the frequency of different malignancies is completely clear. Our aim was to assess the IBD associated malignancies, to collect clinical and mortality data and to analyse possible risk factors. Methods: Data on malignancies developed between January 2015 and May 2019 in Hungarian IBD patients was recorded. Every member of the Hungarian Society of Gastroenterology was prospectively interviewed. The following data were collected: demographic data, disease characteristics, previous therapy, patient adherence, type and localisation of malignancies. Results: 140 IBD patients with newly diagnosed malignancies were reported. 61.4%, 35.7%, and 2.9% of the patients had ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis, respectively. The mean latency was 15.2±10.5 years. Colorectal cancer (CRC) was the most common cancer (49.6%, 70). 72.9% (51/70) of them was associated with UC, more than 80% had extensive (50.9%, 26) and left-sided (31.2%, 16) colitis. The most frequent CRC localisation was the rectosigmoid colon in UC (54.9%), and the rectum in CD (38.9%). The most common non-CRC malignancies were non-melanotic skin-cancer, haematological and pulmonary cancer. Disease duration at the time of the diagnosis of malignancy was lower (17.9±10.7 versus 12.6±9.7 years); mean age at the time of the death was higher (49.3±9.4 versus 64.3±16.4 years); and survival was longer after the diagnosis of extraintestinal malignancy than CRC (0.73±1.01 versus 1.2±0.8). Summary: CRC presented typically in the distal part of the colon by male UC patients with pancolitis or left-sided colitis with a long-standing disease course of IBD. The most common non-CRC malignancies were non-melanotic skin cancer, haematological cancer and lung cancer. Non-CRC malignancies developed typically in female patients, older than CRC patients with shorter disease-course of IBD and longer survival times.

Clinical and Laboratory Characteristics Are Associated With Biologic Therapy Use in Pediatric Inflammatory Bowel Disease: A Retrospective Cohort Study.

BackgroundBiologic agents are a highly useful class of medications for treating inflammatory bowel disease (IBD). Limited evidence exists to guide initiation of biologic therapy, especially in pediatric patients. It is unclear if disease severity is connected to biologic response. We hypothesized that the clinical, biochemical and radiographic characteristics of pediatric IBD at diagnosis were associated with subsequent initiation of biologic therapy.MethodsWe performed a retrospective analysis of the charts of all pediatric patients diagnosed with IBD at our centre over 14 years. Kaplan–Meier curves evaluated patient characteristics at diagnosis with time to initiation of biologic therapy. A Cox proportional hazards model was used for multivariate characteristic analysis.ResultsA total of 198 patients were included, 57.6% had Crohn’s disease, 27.8% had ulcerative colitis and 14.6% had IBD type unclassified. Mean follow-up time was 47.8 months. About 55.5% of the patients received a biologic medication, the mean time to biologic initiation was 21.5 months. Earlier initiation of biologic therapy was frequently associated with older age, higher disease activity index and lower serum albumin.ConclusionsOlder pediatric patients with more severely active disease and lower serum albumin levels at the time of IBD diagnosis were more likely to initiate biologic therapy when considering biologic initiation, even many years after diagnosis. Identification of these characteristics may help inform decisions to initiate biologic therapy earlier in the IBD disease course.