IBD Disease Activity Research Articles

Anti-IFI16 Antibodies in Inflammatory Bowel Disease and Their Variation with Infliximab Therapy in Comparison to Other Modalities of Treatment

Abstract Background Amatory bowel diseases (IBDs) are remittent or progressive conditions that may affect the entire gastrointestinal tract and the colonic mucosa and are associated with an increased risk for colon cancer. Patients with mucosal lesions may not have clinical symptoms, or only present with mild symptoms. Objective measurements are required to assess and monitor IBD disease activity. Moreover responses to treatments must be closely monitored to determine effectiveness and avoid disease complications. Aim of the Work The aim of this study is to assess the utility of IFI16 antibodies as a predictor of infliximab-induced remission in IBD patients in comparison to other modalities of treatment. Patients and Methods A Comparative cross sectional study in internal medicine and gastroenterology outpatient clinic at Ain Shams University Hospital. With 60 IBD patients are included in this study divided into three groups. Results Patients with low levels of IgG antibodies against IFI16 at baseline had a higher probability of a clinical response or remission at the end of induction therapy with IFX (OR 1/4 0.143; 95% CI 0.027–0.761). The only statistically significant association found in patients with UC was that between anti-IFI16 IgG and extensive colitis (E3) (OR 1/4 7.255; 95% CI 2.452–21.463; P 1/4 0.0001) (data not shown). Conclusion Overall, the findings presented in this study deserve more investigation to verify the possibility of exploiting a patient’s reac- tivity against the IFI16 autoantigen as a predictive marker of response to IFX therapy. Anti-IFI16 IgG titers may be of great clinical relevance and provide guidance when tailoring therapeutic choices to individual patients.

Sweet Syndrome Associated with Active Inflammatory Bowel Disease: A Case Series of a Rare Extra-intestinal Manifestation.

Cutaneous extra-intestinal manifestations (EIM) occur in up to 20% of patients with IBD. Information about Sweet syndrome (SS)'s clinical course as a rare cutaneous EIM in IBD is limited to case reports. We present the largest retrospective cohort on the occurrence and management of SS in IBD. Electronic medical records and paper charts since 1980 were retrospectively reviewed at a large quaternary medical center to identify all adult IBD patients with histopathology-proven SS. Patient characteristics and clinical outcomes were evaluated. 25 IBD patients with SS were identified; 3 patients were assessed to have AZA-induced SS. The majority of SS patients were female. Median age at diagnosis was 47years (IQR 33-54years) and SS appeared at a median of 6.4years after IBD diagnosis. IBD patients with SS had a high rate of complicated IBD phenotypes (75% extensive colitis in UC and 73% stricturing or penetrating disease in CD, with 100% colonic involvement), as well as frequent co-occurring EIMs (60%). SS correlated with global IBD disease activity. Corticosteroids were an effective therapy for SS in IBD. Recurrence rate of SS was 36%. Contrary to previous case reports, SS was a cutaneous EIM occurring late after diagnosis of IBD in our cohort, with occurrences paralleling global IBD disease activity. Although AZA-induced and IBD-associated SS were both effectively treated with corticosteroids, distinguishing them is relevant for future IBD treatment strategies.

Effects of intermittent fasting and physical activity on body mass and intestinal inflammation in rats fed a high-fat diet

Obesity has been linked to increased IBD disease activity, lengthened hospital stays, and a higher risk of developing extraintestinal symptoms, according to studies. Therefore, this study aims to evaluate whether intermittent fasting, as well as exercice training on body mass, food intake and intestinal inflammatory in animals feed a high-fat diet. Male wistar rats were used, divided into the following experimental groups: Control Group C (fed with commercial chow), HF group (fed with a high-fat diet), HF + IF Group (fed a high-fat diet associated with Intermittent Fasting), Group C+IF (fed with commercial chow and intermittent fasting) and HF Group +Exercise + IF. The animals were submitted to intermittent fasting protocols of alternate days, in which the animals fasted 24 hours, 3 times a week. A physical activity protocol was applied, where the animals were trained on a programmable treadmill. Body mass and food intake were evaluated weekly and euthanasia and tissue collection were performed at the end of the experiment for morphological evaluation. The results of this study shows that intermittent fasting of alternate days has beneficial effects on adiposity and physiological improvement in the intestine of animals.

A comparison of the Child Health Utility 9D and the Health Utilities Index for estimating health utilities in pediatric inflammatory bowel disease

PurposeHealth utilities are challenging to ascertain in children and have not been studied in pediatric Crohn’s disease (CD) and ulcerative colitis (UC). The objective was to assess discriminative validity by comparing utilities elicited using the Child Health Utility-9 Dimension (CHU9D) to the Health Utilities Index (HUI) across multiple disease activity scales in pediatric UC and CD.MethodsPreference-based instruments were administered to 188 children with CD and 83 children with UC aged 6 to 18 years. Utilities were calculated using CHU9D adult and youth tariffs, and HUI2 and HUI3 algorithms in children with inactive (quiescent) and active (mild, moderate, and severe) disease. Differences between instruments, tariff sets and disease activity categories and were tested statistically.ResultsIn CD and UC, all instruments detected significantly higher utilities for inactive compared to active disease (p < 0.05). Mean utilities for quiescent disease ranged from 0.810 (SD 0.169) to 0.916 (SD 0.121) in CD and from 0.766 (SD 0.208) to 0.871 (SD 0.186) in UC across instruments. Active disease mean utilities ranged from 0.694 (SD 0.212) to 0.837 (SD 0.168) in CD and from 0.654 (SD 0.226) to 0.800 (SD 0.128) in UC.ConclusionCHU9D and HUI discriminated between levels of disease activity in CD and UC regardless of the clinical scale used, with the CHU9D youth tariff most often displaying the lowest utilities for worse health states. Distinct utilities for different IBD disease activity states can be used in health state transition models evaluating the cost-effectiveness of treatments for pediatric CD and UC.

A74 URGENCY FOR BOWEL MOVEMENTS IS A HIGHLY DISCRIMINATORY SYMPTOM FOR ACTIVE DISEASE IN PERSONS WITH IBD (THE MANITOBA LIVING WITH IBD STUDY)

Abstract Background The Inflammatory Bowel Disease Symptom Inventory (IBDSI) is a validated patient self-reported measure used to assess IBD disease activity. Purpose We aimed to assess the prevalence of symptoms, and examine which symptoms are most associated with disease activity as measured by a symptom index and objective measure of inflammation. Method The Manitoba Living with IBD Study is a prospective study of 156 participants with confirmed IBD who completed bi-weekly Inflammatory Bowel Disease Symptom Inventory (IBDSI) surveys. Relative risks (RR) (with 95% confidence interval (CI)), positive and negative predictive values (PPV, NPV), and area under receiver operator curve (AUC) were reported for each symptom to predict active disease defined as: (1) active IBDSI, (2) self-reported flare, and (3) elevated fecal calprotectin (FCAL) (&amp;gt;250µg/g). Analyses were undertaken following stratification based on sex, and disease type (Crohn’s disease (CD) and ulcerative colitis (UC)). Result(s) In total, 69.2% of participants were female; 64.7% had CD. Fatigue was the most prevalent symptom in both inactive and active disease, across all 3 disease measures (IBDSI: 24.5% and 75.1%, self-reported flare: 42.2% and 72.2%, FCAL: 46.0% and 60.6%). Absence of fatigue had a high NPV for active IBDSI and self-reporting a flare in both CD and UC. Urgency had a consistently strong NPV, RR and AUC across all three disease measures in both IBD subtypes and sexes. The number of loose/liquid bowel movements predicted elevated FCAL in UC (RR in men = 3.5, 95% CI 1.2-9.9, RR in women = 1.8, 95% CI 1.2-2.7, AUC in men = 0.73, 95% CI 0.59-0.84, AUC in women = 0.65, 95% CI 0.56-0.72), as did blood in stool in females with UC (RR = 1.8, 95% CI 1.2-2.7). In men with CD, excessive bowel gas (RR = 2.0, 95% CI 1.2-3.4) and urgency (RR = 3.9, 95% CI 1.6-9.3) best predicted an elevated FCAL. No symptom was strongly predictive of elevated FCAL in females with CD. Conclusion(s) Fatigue was the most prevalent symptom irrespective of disease activity. Urgency stood out as being consistently associated with disease activity, irrespective of the disease measure. Individual symptoms have different impacts on subjective (IBDSI) and objective (FCAL) measures in IBD. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

P328 Holistic well-being as Patient-reported outcomes (PROs) in translational IBD research: Prospective capture of CUCQ32 as study endpoints for mechanistic biomarker MUSIC/GIDAMPs study.

Abstract Background There is increasing recognition of ‘holistic’ wellbeing as a key target in the management of IBD. Patient-reported outcomes (PROs) capture the impact of IBD on social, emotional and general wellbeing. Recently, regulatory bodies such as FDA/EMA mandates the study of PROs in interventional clinical trials. However, the role of PROs has never been investigated as a potential end-point in translational scientific research in IBD Methods CUCQ32 is a 32-question form that captures well-being of IBD patients including aspects of fatigue/anxiety/sexual/emotional health – score range from 0-272 (↑score correlating with worse quality QoL). We prospectively captured CUCQ32-PROs in our on-going MUSIC (Cohort 1) and GI-DAMPs (Cohort 2) IBD biomarker studies (www.musicstudy.uk) based in Edinburgh, Glasgow and Dundee (2018-present, ~total n=700 patients recruited). MUSIC is a prospective 12-month longitudinal study (over 5 time points) following active IBD patients in response to current drug treatment whilst GI-DAMPs is a cross-sectional study across IBD disease activity at one-time point. CUCQ32-PROs has been recorded since 2021 with 163 data-points captured. CUCQ32 were filled independently by patients. Results In IBD, CUCQ32-PROs scores were high with medians of 113 (IQR of 67.5-152.2) and 132 (IQR of 91-179) in Cohorts 1 and 2 respectively. In MUSIC Cohort 1, CUCQ32 decreased in response to treatment 113→62→58→45→30 over 3-monthly intervals. CUCQ32 scores are significantly correlated to clinical indices of disease activity, SCCAI for UC (Cohort 1, p=0.003/Cohort 2, p&amp;lt;0.001) and HBI for CD (Cohort 1, p&amp;lt;0.001/Cohort 2, p&amp;lt;0.001). Of interest, no correlation was observed with CRP and faecal calprotectin. Notably, although overall CUCQ32 scores associated with active disease, those deemed in ‘clinical remission’ continue to have high score (median 154 vs. 87 respectively, p=0.06). High CUCQ32 scores were observed even in those achieving complete mucosal healing (defined as either endoscopic SESCD or UCEIS score of 0) from longitudinal prospective endoscopic follow-up; median decrease from 116 (baseline) to 55 (6-months SESCD/UCEIS =0), paired data available in n=14 patients. There is no statistical correlation with endoscopic mucosal healing (p=0.6; in 34 patients). Conclusion Although patient wellbeing improved with medical treatment in IBD and PROs are correlated with clinical indices of IBD activity, high CUCQ32 (thereby poor quality of life) scores were observed in traditional categorisation of ‘clinical remission’. This suggests a far-reaching impact of IBD beyond gut-related signs/symptoms. Our current work incorporates PROs into our scientific biomarker studies and molecular analyses) and will be the first in IBD, to our knowledge.

P835 Visceral adiposity independently predicts time to flare in inflammatory bowel disease, but BMI does not

Abstract Background Obesity is rising globally and has been associated with increased IBD disease severity, prolonged hospital stay and increased development of extra-intestinal manifestations. Measuring “visceral adiposity” by CT scan may be a more meaningful way of classifying obesity compared to traditional measures such as BMI. This study compared visceral adiposity measured by CT scan versus BMI as a predictor of time to IBD flare among patients with CD and UC. Methods This was a retrospective cohort study. Consecutive adults with IBD were included if they had a colonoscopy to evaluate IBD flare and a CT scan within a 30-day window of the colonoscopy from 2010 to 2022. Charts were reviewed until 100 patients with Crohn’s and 100 with UC had been identified. Patients were followed for up to 6 months after the index CT scan for IBD flare, which was characterized by hospitalization/ER visit related to IBD, initiation of steroids, dose escalation, change in IBD medication, or IBD surgery. The primary exposure was the visceral adipose tissue to subcutaneous adipose tissue ratio (VAT:SAT) which was obtained from the index CT scan using TomoVision slicOmatic software. BMI was calculated based on height and weight at the time of the index CT scan. Cox proportional hazard modeling was used to test VAT:SAT and BMI as predictors of time to IBD flare, after adjusting for other factors. Results 100 CD and 100 UC patients were included. The median age was 43 (IQR 31-58), 41% of the population was female, and most were White (55%) or Hispanic (26%). Overall, 20% of the cohort flared with a median time to flare of 88 days (IQR 42.5 – 118.5) among those who flared. For all patients, VAT:SAT was significantly associated with time to flare as seen in Figure 1 (HR 4.8, 95% CI 1.67 to 13.7 for VAT:SAT≥1.0 vs VAT:SAT&amp;lt;1.0), but BMI was not (HR 0.88 95% CI 0.35 to 2.18 for BMI ≥25 vs BMI &amp;lt;25). After stratifying the cohort into CD and UC cohorts, a significant association between VAT:SAT ≥1.0 and time to flare remained for CD (HR 7.68, 95% CI 0.93 – 63.2) but not for UC (HR 0.26, 95% CI 0.018 – 3.70). BMI was not associated with time to flare in either CD or in UC patients (Figure 2). Conclusion Visceral adiposity (VAT:SAT ratio on CT scan) was associated with decreased time to IBD flare, but BMI was not. This relationship may be stronger among Crohn’s compared to Ulcerative colitis patients. Future studies should investigate the mechanisms by which visceral adiposity may contribute to IBD disease activity.

Patient-reported Outcomes and Disability Are Associated with Histological Disease Activity in Patients with Ulcerative Colitis: Results from the APOLLO Study.

Treating beyond endoscopic remission, aiming for histological remission, is an emerging target in ulcerative colitis [UC]. Patient-reported outcome measurements [PROMs] become increasingly important, but their association with histology is unclear. Multiple PROMs were prospectively collected in UC patients undergoing colonoscopy. Mayo endoscopic sub-score [MES] and ulcerative colitis endoscopic index of severity [UCEIS] were determined, as well as the Nancy histological index [NHI] of the most affected area. Endoscopic remission was defined as MES and UCEIS 0, histological remission as NHI 0, and histo-endoscopic mucosal remission [HEMR] as a combination of both. A total of 109 assessments were collected in 80 patients with endoscopic and HEMR remission rates of 24.8% and 16.5%, respectively. Patients with HEMR had a significantly lower overall inflammatory bowel disease [IBD] disability [p <0.001] and disease activity score [p <0.001] as compared with patients without. In line, NHI correlated with the overall IBD-disk [r = 0.36, p <0.001] and simple clinical colitis activity index [SCCAI] score [r = 0.44, p <0.001]. Many individual components of both differed significantly between patients with and without HEMR. Although the overall accuracy of the IBD-disk [0.78] or SCCAI score [0.83] for HEMR is lower [p <0.005] than the MES or UCEIS [0.95], a cumulative IBD-disk score >35.5 and an SSCAI score >3.5 have a high negative predictive value [98.6% and 100.0%, respectively] to exclude HEMR. Histo-endoscopic inactive disease is associated with reduced IBD disability, but not with complete absence thereof. PROMs for disability and clinical disease activity cannot fully replace histo-endoscopic findings, and should be considered complementary in patient-centred endpoint discussions. Nevertheless, PROMs have a high negative predictive value to rule out HEMR.

SAFETY OF PERIOPERATIVE BIOLOGICS IN PATIENTS WITH IBD UNDERGOING RESECTIVE BOWEL SURGERY: THE MUNICH IBD CENTER EXPERIENCE

Abstract BACKGROUND AND AIMS The risk of biologics in the peri-operative setting in IBD is still discussed controversially. Recently, the large prospective PUCCINI trial could demonstrate that direct exposure to TNF-blockers within 12 weeks before abdominal surgery was not associated with a higher risk of infectious complications. However, in daily clinical practice experiences on biological treatment perioperatively are limited. In our current retrospective trial, we addressed the safety of different biologicals in a peri-operative setting. METHODS Eligible IBD patients in this single center study were recruited from our Munich IBD center between January 2012 and May 2022, who underwent bowel surgery at our Department of Surgery. Direct exposure to biologics was defined as exposure to biologics within 12 weeks before abdominal surgery. To evaluate safety, the postoperative outcome focused on minor complications, defined as infectious complications, wound healing complications and major complications, defined as insufficiency of the anastomosis and abscess formation at the surgery site postoperatively. RESULTS A total of 447 IBD patients (334 CD/113 UC, 51.9% female) were included and were followed for a median time of 45 months [range 0-113]. Median age was 44 years [19-89], median age at diagnosis was 24 years [5-84] and median age at surgery was 41 years [16/85]. Median disease duration until surgery was 11 years [0-47]. With 74.3%, the majority of IBD patients had moderate to severe IBD disease activity at date of surgery. A total of 73.9% (326/447) had medical treatment at date of surgery, 61.5% (275/447) were treated with biologics within 3 months before surgery and 42.3% (189/447) had biologics within 4 weeks before surgery. Overall, 36.9% of patients (164/447) received infliximab, 13.0% (58/447) adalimumab, 1.1% (6/447) golimumab, 5.8% (26/447) vedolizumab, 6.5% (29/447) ustekinumab, perioperatively. The majority of surgeries was planned electively (97.1%, 434/447), and performed laparoscopically (67.8%, 303/447). Minor and major postoperative complications occurred in 20.8% (93/447) of patients. Serious complications were observed in a total of 9 patients, six patients had acute bleeding complications postoperatively, 1 patient developed peritonitis and 2 CD patients died postoperatively, one with and one without biologics. No significant differences regarding complications and safety were observed between patients with versus without biologic treatment. Interestingly, CD patients with direct exposure to biologics were more likely to undergo minimal-invasive surgery (63.1%, 135/214) than patients without exposure (28.3%, 34/120, p&amp;lt;0.05). CONCLUSIONS This retrospective single center study of 447 IBD patients could demonstrate that biologic treatment before sugery, even within 4 weeks, is not associated with a higher risk of complications.

Urgency for bowel movements is a highly discriminatory symptom of active disease in persons with IBD (the Manitoba Living with IBD study).

The Inflammatory Bowel Disease Symptom Inventory (IBDSI) is a validated patient self-reported measure used to assess IBD disease activity. There have yet to be more granular analyses on which symptoms are most associated with active disease. To assess the prevalence of symptoms, and to examine which are most associated with disease activity as measured by a symptom index and objective measure of inflammation METHODS: The Manitoba Living with IBD Study is a prospective study of 156 participants with confirmed IBD who completed bi-weekly IBDSI. Relative risks (RR) and predictive values (NPV and PPV) were reported for each symptom to predict active disease defined as active IBDSI, self-reported flare and elevated faecal calprotectin (FCAL) (>250 μg/g). Analyses were undertaken following stratification based on sex, and disease type (Crohn's disease [CD] and ulcerative colitis [UC]). In total, 69.2% were female; 64.7% had CD. Fatigue was the most prevalent symptom in both inactive and active disease, across all three disease measures (IBDSI: 24.5% and 75.1%, self-reported flare: 42.2% and 72.2%, FCAL: 46.0% and 60.6%). The absence of fatigue had a high NPV for active IBDSI and self-reporting a flare in both CD and UC. Urgency had a consistently strong NPV and RR across all three disease measures in both IBD subtypes and sexes. The number of loose/liquid bowel movements predicted elevated FCAL in UC (RR males=3.5, 95% CI 1.2-9.9, RR females=1.8, 95% CI 1.2-2.7), as did blood in stool in UC females (RR=1.8, 95% CI 1.2-2.7). In males with CD, excessive bowel gas (RR=2.0, 95% CI 1.2-3.4) and urgency (RR=3.9, 95% CI 1.6-9.3) best predicted an elevated FCAL. No symptom was strongly predictive of an elevated FCAL in CD females. Urgency was consistently associated with disease activity, irrespective of the disease measure. Fatigue was the most prevalent symptom irrespective of disease activity measure. Individual symptoms have different impacts on subjective (IBDSI) and objective (FCAL) measures in IBD.

The Impact of COVID-19 on Patients with IBD in a Prospective European Cohort Study.

Background and AimsThere are concerns regarding the potential impact of the COVID-19 outbreak on patients with inflammatory bowel disease [IBD]. We report on the impact of the COVID-19 outbreak in a European prospective cohort study of patients with IBDPatients and MethodsWe prospectively collected data from 5457 patients with IBD nested in the ongoing I-CARE project and still followed up in April 2020, with monthly online monitoring of clinical activity, treatment, imaging and endoscopy. Investigators were also contacted to report incidental cases.ResultsIn total, 233 [4.3%] reported COVID-19 and 12 [0.2%] severe COVID-19, with no COVID-19 deaths. The risk of COVID-19 in patients with IBD was not increased compared to the general population (standardized incidence ratio [SIR]: 1.18, 95% confidence interval [CI] [1.03–1.34], p = 0.009), as well as the risk of severe COVID-19 (SIR: 0.69, 95% CI [0.35–1.20], p = 0.93). We did not observe any negative impact of the different IBD-related medication on the risk of either COVID-19 or severe COVID-19. In 2020, the COVID-19 outbreak resulted in a drastic decrease in endoscopic and imaging procedures from March to May 2020 compared to 2018 and 2019. No impacts on clinical IBD disease activity as well as ongoing treatment were noted.ConclusionNo increases in either COVID-19 or severe COVID-19 incidences were observed in patients with IBD. There was no impact of COVID-19 on IBD-related medication and clinical activity. Access to endoscopy and imaging was restricted during the first months of the first COVID-19 outbreak.

Long-Term Dietary Patterns Are Reflected in the Plasma Inflammatory Proteome of Patients with Inflammatory Bowel Disease.

Diet plays an important role in the development and progression of inflammatory bowel disease (IBD, comprising Crohn’s disease (CD) and ulcerative colitis (UC)). However, little is known about the extent to which different diets reflect inflammation in IBD beyond measures such as faecal calprotectin or C-reactive protein. In this study, we aimed to unravel associations between dietary patterns and circulating inflammatory proteins in patients with IBD. Plasma concentrations of 73 different inflammation-related proteins were measured in 454 patients with IBD by proximity extension assay (PEA) technology. Food frequency questionnaires (FFQ) were used to assess habitual diet. Principal component analysis (PCA) was performed to extract data-driven dietary patterns. To identify associations between dietary patterns and plasma proteins, we used general linear models adjusting for age, sex, BMI, plasma storage time, smoking, surgical history and medication use. Stratified analyses were performed for IBD type, disease activity and protein intake. A high-sugar diet was strongly inversely associated with fibroblast growth factor-19 (FGF-19) independent of IBD type, disease activity, surgical history and deviance from recommended protein intake (false discovery rate (FDR) < 0.05). Conversely, a Mediterranean-style pattern was associated with higher FGF-19 levels (FDR < 0.05). A pattern characterised by high alcohol and coffee intake was positively associated with CCL11 (eotaxin-1) levels and with lower levels of IL-12B (FDR < 0.05). All results were replicated in CD, whereas only the association with FGF-19 was significant in UC. Our study suggests that dietary habits influence distinct circulating inflammatory proteins implicated in IBD and supports the pro- and anti-inflammatory role of diet. Longitudinal measurements of inflammatory markers, also postprandial, are needed to further elucidate the diet–inflammation relationship.

Work-Related Productivity Loss and Associated Indirect Costs in Patients With Crohn's Disease or Ulcerative Colitis in the United States.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affects an estimated 1.6 million US adults, and results in humanistic and economic burden even among mild patients, which grows with increasing disease activity. Gastroenterologists and their IBD patients provided real-world data via US IBD Disease Specific Programmes 2014-2018. Patients with physician- and patient-reported data completing a Work Productivity and Activity Impairment questionnaire were categorized by disease activity, defined using Crohn's Disease Activity Index (CD) and partial Mayo scores (UC), respectively. Associations of disease activity with patient-reported productivity loss and indirect costs were assessed. The analyses included 281 patients with CD and 282 patients with UC. Mean ages were 40.0 and 40.5 years, and mean disease durations 7.1 and 5.4 years, for CD and UC, respectively. In CD, absenteeism (0.95%-14.6%), presenteeism (11.7%-44.9%), and overall work impairment (12.4%-51.0%) increased with increasing disease activity (all P < .0001). In UC, absenteeism (0.6%-11.9%), presenteeism (7.1%-37.1%), and overall work impairment (7.5%-41.9%) increased with increasing disease activity (all P < .0001). Annual indirect costs due to total work impairment increased with increasing disease activity (all P < .0001), from $7169/patient/year (remission) to $29 524/patient/year (moderately-to-severely active disease) in CD and $4348/patient/year (remission) to $24 283/patient/year (moderately-to-severely active disease) in UC. CD and UC patients experienced increased absenteeism, presenteeism, and overall work impairment with increasing disease activity, resulting in higher indirect costs. Treatments significantly reducing IBD disease activity could provide meaningful improvements in work productivity and associated costs.

P656 The impact of periodontitis on IBD disease activity

Abstract Background Inflammatory bowel disease (IBD) and periodontitis are chronic, progressive, inflammatory diseases with similarities in their respective pathogenesis, which involve a complex interplay between a dysbiotic microbiota and a dysregulated immune-inflammatory response. Periodontitis has been associated with an adverse impact on other inflammatory diseases and the general health. Whether presence of periodontitis is associated with IBD disease activity is uncertain. Methods A questionnaire-based survey was conducted in Denmark. A total of 1,093 patients with IBD, i.e., 527 patients with Crohn’s disease (CD) and 566 patients with Ulcerative colitis (UC), answered the questionnaire. The survey included questions on social demographics, oral health, as well as IBD-related characteristics. Oral health was assessed by the number of teeth, the state of teeth and gums, and the Periodontal Screening Score (PESS) which is a validated instrument to screen for severe periodontitis. Disease activity in patients with UC and CD was assessed by the Simple Clinical Colitis Index (SCCAI) and the Harvey &amp; Bradshaw’s Activity Index (HBI), respectively. Disease related disability was assessed by the Inflammatory bowel disease disability index (IBD-DI). Univariate and multivariate statistical analyses were performed to assess each variable. Results Patients with CD reported significantly fewer remaining teeth (p=0.004) and poorer state of teeth and gums (p=0.001) in comparison to patients with UC. Irrespective of IBD disease subtype, patients with a reduced number of teeth scored significantly higher on the IBD disability index (p=0.001) and reported an increased disease activity in the last 12 months (p=0.001). Patients with self-reported severe periodontitis scored significantly higher on the IBD disability index (p=0.041) and reported an increased disease activity in the last 12 months (p=0.001). For patients with UC, self-reported severe periodontitis was associated with a higher SCCAI score (p=0.031). Likewise, patients with CD who had a reduced number of teeth scored significantly higher on the HBI (p=0.017). Conclusion Periodontitis was significantly associated with increased IBD disease activity as well as increased IBD disease related disability. CD patients had significantly poorer oral health compared with UC patients. Our results highlight a need for an increased focus on oral health in patients with IBD.

OP09 Patient reported outcomes reflect histologic disease activity in patients with Ulcerative Colitis: Interim analysis of the APOLLO study

Abstract Background Treating beyond endoscopic remission, aiming for histological remission, has shown to reduce relapse and hospitalization rates in patients with ulcerative colitis (UC). However, very little is known on how histological remission associates with patient reported outcomes (PROMs). Methods PROMs (Simple clinical colitis activity index [SCCAI], IBD disk and Visual Analogue Scales [VAS]) were prospectively collected through a digital questionnaire in all patients with UC undergoing colonoscopy between July 21st 2020-Jan 21st 2021. Mayo endoscopic sub score and UCEIS were determined, as well as the Nancy histologic index (NHI) of the most affected area. Endoscopic remission was defined as Mayo endoscopic sub score 0 and UCEIS 0; histologic remission as NHI 0, absence of active inflammation as NHI ≤ 1. PRO2 remission was defined as stool frequency ≤ 1 (absolute stool frequency ≤ 3 OR 1–2 stools more than usual) and rectal bleeding score of 0. Results Fifty-six paired assessments were collected in 48 unique patients (Table 1), with a histologic, endoscopic and PRO-2 remission rate of 23.2%, 28.6% and 38.2% respectively. Patients with histologic remission or absence of histologic inflammation had a significantly lower overall IBD disability (p=0.007, p=0.003) and disease activity score (p=0.003, p&amp;lt;0.001), as compared to patients without. In line, NHI correlated with the overall IBD disk (r=0.40, p=0.002) and SCCAI score (r=0.50, p&amp;lt;0.001). Many individual components of both scores (abdominal pain, arthralgia, impact on education and work/interpersonal interactions/sexual function, regulation of defecation, blood loss, general wellbeing, joint pain, numbers of stools during night/day, urgency) differed significantly between patients with and without histologic remission. VAS scores assessing general wellbeing (r=0.33, p=0.01), impact on daily activities (r=0.41, p=0.002), UC-related symptoms (r=0.42, p=0.001) and worries (r=0.40, p=0.002) correlated with histology. Quartile analysis of the overall IBD disk and SCCAI scores confirmed the highest likelihood for histologic remission in patients with the lowest scores (Q1-Q2 vs Q3-Q4 39.3% vs 7.1%, p=0.01; 40.0% vs 9.7%, p=0.01) (Figure 1). Nevertheless, the overall accuracy of the IBD disk (0.75) or SCCAI score (0.76) for histologic remission is lower (p&amp;lt;0.05) than the accuracy of the Mayo endoscopic (0.90) or UCEIS (0.90) score. Table 1: Baseline features Abstract OP09 – Figure 1: Quartile analysis Conclusion In patients with UC, PROMs for disability and clinical disease activity reflect histologic disease activity and should therefore be further explored in (trial) endpoint discussions. However, they cannot fully replace endoscopic and histologic findings, and should be considered complementary.

N10 Experience with telemedicine during the COVID-19 pandemic and preferences for future e-health in a large IBD cohort

BackgroundThe COVID-19 pandemic affects clinical care, daily life and wellbeing of patients with IBD. During the contact restrictions, we realized anxiety among our IBD patients and unmet needs for healthcare. We investigated patient’s experience with telemedicine (TM) during the pandemic, their interest in future TM use, and their preference regarding a qualified IBD Nurse-led or a Medical Doctor-led (MD-led) teleconsultation at a large German IBD center.MethodsPediatric and adult patients who attended the IBD unit at least once between 7/2018 and 6/2020) were invited to a prospective survey (KoCo19-CED-1). Questions included items on IBD (phenotype, treatment and disease activity), comorbidities, healthcare utilization, demographic and socioeconomic factors, psychological burden and IBD-related quality of life during the COVID-19 pandemic. This sub-analysis presents patient’s experience with TM and their preference for a contact with an IBD Nurse.ResultsOf 820 identified IBD cases, 504 (62%) patients and/or their parents completed the survey between mid-July to mid-October 2020; 86 were children (aged 6 to 18 years) and 418 were adults (up to 85 years); 58.7% had Crohn’s disease and 35.7% Ulcerative Colitis. Current treatment with any immunosuppressive medication (mono- or combo-therapy with immunomodulators, biologics, JAK-inhibitors and/or corticosteroids) were reported by 79.6% (401/504) of patients. During the pandemic, an in-person visit was substituted with TM by an IBD Nurse or a medical doctor (MD) in 58 (11.6%) and 29 (5.8%) of the patients, with high satisfaction (88.5% vs 92.1 %, respectively, n.s.). Half of the patients (n=246) showed interest in future TM, thereof 60.2% preferred consultation with a MD, 1,6% with an IBD Nurse and 38.2% expressed no preference. Of patients with prior experience with an IBD Nurse-led TM (n=38), 96% are interested to use TM in the future. Rejection of future TM was related to no TM experience (p=0.001), having Crohn’s disease (p=0.032), receiving biologics (p=0.004), and self- or non-employment status (p=0.003), but not to gender, age, self-reported disease activity or disease duration.ConclusionPatient acceptance of TM is high, particular in those with previous TM experience, regardless of performed by MD or IBD Nurse. Our data support the statement on e-health in the N-ECCO 2018 Consensus giving an advanced IBD Nurse alongside with MD a key role to improve IBD care.

P330 Long-term outcomes following a switch from originator adalimumab to the biosimilar SB5 (Imraldi) in IBD

Abstract Background Multiple adalimumab (ADA) biosimilars, including SB5 (Imraldi) and ABP 501 (Amgevita), are now approved for use in IBD. Data about biosimilar ADA in IBD remain scarce. We therefore aimed to investigate long-term outcomes of the biosimilar SB5 in IBD patients following a switch from the ADA originator (Humira) or after start of SB5 as their first ADA-therapy. Methods We performed a retrospective cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5 regardless of IBD phenotype, disease activity and ADA dosing. All patients were reviewed regularly in the virtual biologics clinic with protocol driven collection of clinical disease activity, blood tests, TDM and faecal calprotectin. We identified all patients on SB5 in a biologic prescription database that prospectively registered all ADA by brand name and start and stop dates. Results 441 patients were treated with SB5, including 234 who switched from Humira to SB5 (CD=209, 89.3%; median IBD duration 10 years, IQR 6-16) and 207 who started on SB5 as their first ADA-therapy (CD=162, 78.3%; median IBD duration 6 years, IQR 1-16.8). 107/234 (45.7%) patients who switched to SB5 used infliximab before ADA. These patients were treated for a median of 32 months (IQR 17-57) with Humira prior to switching. At Humira – SB5 switch, 60.1% (140/234) received 40mg ADA every other week and 39.1% (91/234) once weekly. The median duration of follow up was 13 months (IQR 8-14). At week 26 and week 52, 194/231 (84.1%) and 148/215 (70.3%) patients remained on SB5, respectively (Figure 1). 81/234 patients (35.0%) discontinued SB5, mostly due to adverse events (n=40/81) or secondary loss of response (n=35/81). Pain at the injection site was the most frequently reported adverse event (n=31); all these patients switched to Amgevita. 30/31 patients with a double biosimilar continued Amgevita until the end of follow up (median 30 months), resulting in 172/215 (81.3%) patients that remained on ADA at week 52 (Figure 1). Proportions of patients in biochemical remission and clinical remission were similar at baseline, week 26 and week 52 following switch (Figure 2). Median ADA trough levels were similar before (10.2 ug/ml, IQR 7.4-13.5) and after switch 10.3 (IQR 7.4-13.1). 17/234 (7.3%) patients developed antibodies during SB5 treatment. Conclusion Switching from Humira to SB5 appeared effective and safe in this study with over 12 months of follow up. The most common adverse event was injection site pain; these patients were successfully moved on to Amgevita providing the first data about a double biosimilar switch. Over the 24 months of this biosimilar ADA program substantial cost savings were effected.

P655 Insulin Resistance Prevalence is Not Increased in Patients with Inflammatory Bowel Disease: a case-control study

Abstract Background Inflammatory bowel disease (IBD) is considered a chronic inflammatory state that has been associated with nonalcoholic fatty liver disease (NAFLD). Insulin resistance (IR) has been linked to NAFLD and inflammation. Whether if IR is prevalent in IBD and increases the risk of NAFLD in these patients is unknown. We aimed to study if IR is prevalent in a cohort of patients with IBD and associated risk factors. Methods This multicentric cross-sectional study compared 151 IBD patients with 174 age matched non-diabetic controls. Insulin and C-peptide serum levels and IR and beta cell function (%B) indices by homoeostatic model assessment (HOMA2) were evaluated. In the IBD patients fatty liver disease (FLD) was assessed by ultrasound (Grade I-IV) and Transition elastography (Fibroscan ®, values were correlated to liver fibrosis as: &amp;lt;7.6 KPa=F0-F1, 7.7–9.4 KPa=F2, 9.5-14KpPa =F3, &amp;gt;14KPa =F4). .Anthropometric, IBD characteristics, biochemical parameters and concomitant diseases were registered as predictive factors for having IR among IBD patients and assessed by multivariable regression analysis. Results IBD patients (57% female, mean age 48 years(SD 10)), compared to matched controls (68% female, mean age 50 years(SD 16)) exhibited similar HOMA2-IR (0.97 ± 0.64 vs 1.31 ± 0.80, p=0.19) and HOMA2-%B indexes (126 ± 49 vs 134 ± 47, p=0.31) after adjusting by confounders. Obesity, abdominal circumference and triglycerides were associated with the presence of IR in IBD patients, whereas IBD disease patterns, disease activity and inflammatory markers were not related to IR. Mild and moderate FLD was present in 26% and 13 % of IBD patients, respectively. FLD grades correlated with a higher insulin and C-peptide and IR indices as observed in the univariable analysis for HOM2-IR (0.06 (0.01–0.11)) and for HOM2-%B 6(3–10) indices. Patients with severe fat infiltration had higher serum levels of insulin and C-peptide and a superior HOM2-IR (2.4 ± 1.6, p=0.01) and HOMA2-%B (251 ± 40, p&amp;lt;0.001) indices compared to mild steatosis. Moreover, adjusted trend analysis showed significant values for C-peptide and HOMA2-%B, showing, therefore, that as FLD grades increases higher values of both also rises. Conclusion IBD patients show a similar prevalence of IR compared to controls. However, likewise in the general population, metabolic syndrome factors are associated with IR and FLD, so metabolic syndrome assessment is mandatory among IBD patients.

An Overview of Tools to Score Severity in Pediatric Inflammatory Bowel Disease

Background and Aims: The management of IBD entails the use of various treatments (nutrition, medications, and surgery) in order to induce and maintain remission. The assessment of IBD disease activity is based on a combination of symptoms, clinical findings, imaging, and endoscopic procedures. As in any disease, reliable assessment of disease activity or severity is required in order to plan relevant follow-up, decide on appropriate investigations, determine the best treatment option and subsequently assess response to treatment. It is important for proper documentation, follow-up, assessment of response to treatment and communication, especially in patients with IBD, to talk the same language by using validated and widely used scores for disease activity, endoscopic and radiologic activity, and patient reported outcomes both for clinical practice and research. This review aims to highlight key tools available for the assessment of disease activity or severity in individuals (especially children) with IBD.Methods: A literature search was performed using MEDLINE, Pubmed, and the Cochrane Library with the last search date of August 2020. Tools evaluating disease severity across various aspects (clinical, endoscopic, and radiological) were identified and discussed. Those tools validated and specific for children with IBD were included were available.Results: Over time a number of scoring systems have been developed to quantify clinical, endoscopic and imaging assessments in individuals with IBD. While some are exclusively for children or adults, others appear to have relevance to all age groups. In addition, some tools developed in adult populations are utilized in children, but have not expressly been validated in this age group.Conclusions: Although some available scoring tools are appropriate for children with IBD, others require consideration. The development and use of pediatric-specific tools is relevant and appropriate to optimal care of children and adolescents with IBD.

Chronic pain in patients with inflammatory bowel disease.

Crohn’s disease and ulcerative colitis (“inflammatory bowel disease” [IBD]) are chronic relapsing intermittently acute conditions, characterised by pathological changes in gut tissue, symptoms of diarrhoea, blood loss, and abdominal pain, long-term complications (fistulae, abscesses, and strictures), extra-abdominal manifestations such as arthritis, and systemic illness. Symptoms dominate IBD disease activity indices,39,42 but the primary target for treatment is inflammation of the gut mucosa. This treatment has significantly improved over the past decade, notably through the use of immunomodulator and biologic drugs. However, the pattern, severity, impact, and prognosis of symptoms still vary substantially from patient-to-patient. Clinicians caring for people with IBD focus on controlling the active bowel disease. Objective measures of disease activity, using endoscopy and imaging or surrogates such as faecal calprotectin, provide targets for disease-modifying drugs in trials and the clinic. However, there is a discrepancy between measures of gut inflammation and the extent and severity of patients' symptoms,30 and neither are straightforwardly related to measures of the overall impact on patients' lives.30 Early mucosal healing defined by endoscopy is associated with long-term improvements in symptom severity, but one-third of patients with healed mucosa do not achieve clinical remission.76,77 In particular, abdominal pain that persists beyond flares, despite optimal treatment of the gut disease, presents a common, disabling, and unresolved problem,64,101 affecting patients' quality of life (QoL) and psychological well-being58,75 and posing challenges for management.66,87 For clinicians, this means disease-targeted treatment alone may not resolve the patient's pain and pain-related distress. The result is that chronic abdominal pain may dominate patients' lives—underrecognised in both specialist and primary care settings, poorly assessed, and inadequately treated. In this Topical Review, we consider evidence about chronic abdominal pain in people with IBD. Our aim was to identify the extent to which general principles of modern chronic pain management92 should have equal place in the IBD clinic and consultation alongside the clinician's concern for diagnosing and treating underlying gut pathology, to ensure that pain in all patients with IBD is properly recognised, formally assessed, and treated safely and effectively.