Inflammatory Bowel Disease Population Research Articles

Antibody Response 3 Months After 2-Dose SARS-CoV-2 mRNA Vaccination in Patients With Inflammatory Bowel Disease.

The response to SARS-CoV-2 vaccination of patients with inflammatory bowel disease (IBD) on immune-modifying therapies requires further investigation because previous studies indicate that patients on immune therapy might have decreased antibody concentrations. We present the antireceptor binding domain antibody response over a period of 3 months in 217 patients with IBD who completed standard 2-dose SARS-CoV-2 mRNA vaccine series. Almost all (98.6%) IBD vaccine recipients had a positive antireceptor binding domain antibody response at least 3 months after vaccination. Decreased antibody titers at 3 months were seen in a subset of patients on antitumor necrosis factor-alpha. Approximately 10% of the participants with high-titer antibodies at 1 month had a decrease to low-positive titers at 3 months, which was mostly observed in those on combination therapy and antitumor necrosis factor-alpha monotherapy. Larger longitudinal studies are required to define the response in IBD population and its clinical impact.

Increased Prevalence of Myocardial Infarction and Stable Stroke Proportions in Patients with Inflammatory Bowel Diseases in Quebec in 1996-2015.

Background: Chronic inflammatory diseases are linked to an increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is controversial. We therefore examined the risk of and risk factors for myocardial infarction (MI) and stroke in IBD patients. Methods: We used the public health administrative database from the Province of Quebec, Canada, to identify IBD patients newly diagnosed between 1996 and 2015. The incidence and prevalence of MI and stroke in IBD patients were compared to those for the Canadian population. Results: A cohort of 35,985 IBD patients was identified. The prevalence but not incidence rates of MI were higher in IBD patients (prevalence: 3.98%; incidence: 0.234) compared to the Canadian rates (prevalence: 2.0%; incidence: 0.220), while the prevalence and incidence rates of stroke were not significantly higher in the IBD patients (prevalence: 2.98%; incidence: 0.122, vs. Canadian rates: prevalence: 2.60%; incidence: 0.297). We identified age, female gender, hyperlipidemia, diabetes, and hypertension (p < 0.001 for each) as significant risk factors associated with MI and stroke in IBD. Exposure to biologics was associated with a higher incidence of MI (IRR: 1.51; 95% CI: 0.82–2.76; p = 0.07) in the insured IBD population. Conclusions: An increased prevalence but not incidence of MI and no increased risk of stroke were identified in this population-based IBD cohort.

Polygenic risk and causal inference of psychiatric comorbidity in inflammatory bowel disease among patients with European ancestry

BackgroundApproximately 40% of persons with inflammatory bowel disease (IBD) experience psychiatric comorbidities (PC). Previous studies demonstrated the polygenetic effect on both IBD and PC. In this study, we evaluated the contribution of genetic variants to PC among the IBD population. Additionally, we evaluated whether this effect is mediated by the expression level of the RBPMS gene, which was identified in our previous studies as a potential risk factor of PC in persons with IBD.Materials and methodsThe polygenic risk score (PRS) was estimated among persons with IBD of European ancestry (n = 240) from the Manitoba IBD Cohort Study by using external genome-wide association studies (GWAS). The association and prediction performance were examined between the estimated PRS and PC status among persons with IBD. Finally, regression-based models were applied to explore whether the imputed expression level of the RBPMS gene is a mediator between estimated PRS and PC status in IBD.ResultsThe estimated PRS had a significantly positive association with PC status (for the highest effect: P-value threshold = 5 × 10–3, odds ratio = 2.0, P-value = 1.5 × 10–5). Around 13% of the causal effect between the PRS and PC status in IBD was mediated by the expression level of the RBPMS gene. The area under the curve of the PRS-based PC prediction model is around 0.7 at the threshold of 5 × 10–4.ConclusionPC status in IBD depends on genetic influences among persons with European ancestry. The PRS could potentially be applied to PC risk screening to identify persons with IBD at a high risk of PC. Around 13% of this genetic influence could be explained by the expression level of the RBPMS gene.

Proportionate Cardiovascular Mortality in Chronic Inflammatory Disease in Adults in the United States From 1999 to 2019.

Despite a rising prevalence of chronic inflammatory disease (CID), the recent trends in cardiovascular disease (CVD) mortality of patients with CID is scarce. In this study, we investigated patterns of CVD mortality in systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) compared with the general population. We used the 1999 to 2019 multiple causes of death files from the national center for health statistics to analyze patterns and trends of proportionate CVD mortality in CID compared with the general population. We analyzed a total of 11,154 CVD deaths in IBD, 58,337 CVD deaths in RA, 6227 CVD deaths in SLE, and 17,826,871 CVD deaths in the general population. Between 1999 and 2019, we found that proportionate CVD mortality decreased significantly in the IBD group (25% to 16%), RA group (34% to 25%), and the general population (41% to 31%), but did not change for the SLE group (15% to 15%). Patients with SLE who died of CVD were approximately 10 years younger compared with CVD decedents with RA, IBD, or general population. The White population had higher proportionate CVD mortality than African American (IBD [19% vs 16%-18%] and SLE [14%-16% vs 12-14%], respectively). This study identifies current trends in CVD mortality in the CID population and elucidates current demographics in CVD mortality in CID. Although proportionate CVD mortality decreased in the general population, and in patients with RA and IBD, there was no change among patients with SLE. Further studies are needed to elucidate these differences.

RELATIONSHIP BETWEEN SELF-REPORTED SLEEP AND DISEASE ACTIVITY DIFFERS BASED ON ENDOSCOPIC OR CLINICAL DISEASE ACTIVITY MEASURES

Abstract BACKGROUND Patients with inflammatory bowel disease (IBD) report more sleep disturbances than healthy controls. Self-reported sleep disturbances have been associated with active clinical disease. Few studies have examined the relationship between self-reported sleep and endoscopic disease activity, and IBD sleep studies have yet to consider the discrepancies that exist between clinical and endoscopic disease measures. The purpose of this pilot study was to examine self-reported sleep based on endoscopic and clinical disease activity among patients with IBD. METHODS Patients with IBD were recruited from a single medical center. Patients ages 18-55 with a scheduled endoscopy were included. Patients completed informed consent, wore a wrist actigraph for 10 days, and answered baseline demographic, clinical disease activity, and sleep questionnaires including Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance, PROMIS sleep-related impairment, and the Pittsburg Sleep Quality Index (PSQI). For both the PROMIS and PSQI, higher scores indicate greater sleep/wake disturbances. Endoscopic disease activity (Mayo or Simple Endoscopic Score) within three months was obtained from the medical record. RESULTS The study included 27 participants with a mean age of 33.3 (SD: 8.2) years and a disease duration of 11 (SD: 7.2) years. The sample predominantly had Crohn’s disease (75%) and 61% were female. Sixty-three percent of the total sample were classified as poor sleepers based on the PSQI. When comparing self-reported sleep based on clinical disease activity, patients with active clinical disease had higher self-reported sleep disturbance (57.3 vs. 49.7, D=1.28) and sleep-related impairment (58.1 vs. 52.8, D=0.51) compared to those with inactive clinical disease. However, self-reported sleep and endoscopic disease activity had the opposite interpretation. Only 40% of patients with active endoscopic disease were poor sleepers compared to 76.5% of patients with inactive endoscopic disease. Patients with active endoscopic disease had lower self-reported sleep disturbance (49.2 vs 52.6, D=-0.53) and sleep-related impairment (49.7 vs. 56.6, D=-0.71) compared to those with inactive endoscopic disease. CONCLUSION The relationship between self-reported sleep and disease activity differs based on the measure of disease activity. Our findings of self-reported sleep disturbances and active clinical disease are similar to previous studies. However, when examining the relationship based on endoscopic disease activity, patients with active endoscopic disease had less self-reported sleep disturbance than patients with inactive endoscopic disease. Further research is needed to better characterize the relationship between sleep and disease activity, and determine the underlying mechanisms related to poor sleep in the IBD population.

THE OPIOID EPIDEMIC: ASSESSING OUTCOMES OF OPIOID ABUSE IN CHRONIC INFLAMMATORY DISEASE (ULCERATIVE COLITIS VS CROHN’S DISEASE)

Abstract BACKGROUND The use of Opiates in patients with Inflammatory Bowel Disease (IBD) has been studied previously. However, to our knowledge, no studies have compared outcomes between patients with opioid abuse with ulcerative colitis (UC) versus patients with opioid abuse and concomitant Crohn’s disease (CD). Our study aims to investigate the impact on hospital mortality, hospital length of stay (LOS), and total charges between both patient groups. METHODS All patients aged 18 years and above with UC and CD as well as opiate abuse disorder, from 2016-2019 were identified from the US Nationwide Inpatient Sample (NIS). The NIS is a large, publicly available all-payer inpatient care database in the USA. The primary outcome evaluated was inpatient mortality. Multivariate regression analysis was used to estimate the odds ratios of in-hospital mortality, the average length of hospital stay, and hospital charges, after adjusting for age, gender, race, primary insurance payer status, hospital type and size (number of beds), hospital region, hospital teaching status, and other demographic characteristics. STATA software was used for analysis. RESULTS Among 35,734 patients who had opioid abuse, 7,980 (22.3%) patients had UC and 27,949 (77.7%). The adjusted odds ratio (OR) for both inpatient mortality (OR 1.13, p=0.692) and hospital length of stay (LOS) (+0.62 days, p=0.09) for opioid abuse with UC compared to those with Crohn’s disease were not statistically significant. However, total hospital charges were $8,649 higher (p&amp;lt;0.018) in patients with UC. Independent positive predictor of increased mortality was older age (p&amp;lt;0.0001). Independent positive predictors of increased LOS and total hospital charges were the following: fistula formation (+10.1 days, +$118,312, p&amp;lt;0.001 for both), bowel obstruction (+2.5 days, p&amp;lt;0.006; +$16,685, p&amp;lt;0.036), hematochezia (+3.1 days, p&amp;lt;0.02; +$30,168, p&amp;lt;0.018), electrolyte abnormalities (+2.0 days, p&amp;lt;0.001; +$26,450, p&amp;lt;0.0001), colonoscopy (+2.5 days, p&amp;lt;0.001; +$19,102, p&amp;lt;0.005), bowel resection (+11.9 days, p&amp;lt;0.0001; +$131,750, p&amp;lt;0.0001). Total charges were also increased for white patients (+$13,236, p&amp;lt;0.016), black patients (+$28,070, p&amp;lt;0.008), Hispanic patients (+$25,970, p&amp;lt;0.0008). CONCLUSION Our study shows that there is no difference in mortality or LOS in patients with opioid abuse with UC versus those with CD. However, total charges are significantly higher for UC patients with opioid abuse. Also, elderly patients with UC are at increased risk for mortality. Opioid abuse in the IBD population is common, given that symptoms of disease activity often include pain. However, the abuse of opiates has led to an opioid crisis in the United States. It is interesting to note the disparity between patients with UC vs CD. This needs to be studied further in randomized trials to help mitigate adverse outcomes in this patient population.

FEAR OF THE COVID-19 PANDEMIC IN ADOLESCENTS AND YOUNG ADULTS WITH INFLAMMATORY BOWEL DISEASE: RELATIONSHIP TO PSYCHOLOGICAL AND PHYSICAL OUTCOMES

BACKGROUNDThe fear of contracting COVID-19 has taken a significant toll on the psychological and physical health of adolescents and young adults (AYA), especially those with chronic health conditions. AYA with Inflammatory Bowel Disease (IBD) are at increased risk for poor psychological and physical well-being. However, to date, there is no published research examining the Fear of COVID-19 Scale (FCV-19S) in AYA with IBD.AIMSTo assess: 1) the reliability of the Fear of COVID-19 Scale in AYA with IBD, and 2) how the fear of COVID-19 relates to key psychological (i.e., anxiety, depression) and physical (i.e., fatigue, pain, disease activity) outcomes in AYA with IBD.METHODSThis ongoing study is a collaboration between Stanford University and ImproveCareNow. Participants included 64 AYA with IBD (M=18.7 years old; 52% Ulcerative Colitis; 60% female; 60% White). Participants completed a one-time online survey. Correlation analyses examined the association between fear of COVID-19, outcome variables (i.e., anxiety, depression, fatigue, pain, disease activity), and demographic variables. Multiple linear regression (MLR) analyses (using the F test) further examined the association between fear of COVID-19, outcome variables, and significant demographic variables (i.e., age, sex).RESULTSThe internal reliability of FCV-19S was measured using Crohnbach’s alpha (α=0.88), indicating high internal consistency. Correlation analyses demonstrated that fear of COVID-19 was significantly associated with anxiety, depression, and fatigue (Table 1). The overall MLR models were significant for anxiety (P<0.001), depression (P=0.002), and fatigue (P=0.031), but not for pain and disease activity. Fear of COVID-19, age, and sex accounted for 29% of the variance in anxiety, 27% of the variance in depression, and 17% of the variance in fatigue. Fear of COVID-19 was not a significant independent predictor of outcomes (Table 2). Female sex was a significant independent predictor for greater levels of anxiety (b=-0.31, P=0.016) and depression (b=-0.35, P=0.008). Older age was a significant independent predictor for greater levels of depression (b=0.29, P=0.031).CONCLUSIONPreliminary results suggest that FCV-19S can be reliably assessed in AYA with IBD. Analyses indicate that fear of COVID-19 is associated with anxiety, depression, and fatigue in AYA with IBD. While COVID-19 fear may be important in explaining these outcomes, female sex independently predicted increased anxiety and depression, and older age independently predicted depression. This highlights the importance of assessing relevant demographic variables (e.g., female sex, young adults) when considering predictors of adjustment in AYA with IBD. Research should further investigate fear of COVID-19 in larger, more diverse IBD populations to better understand its relationship to key IBD outcomes.

P666 Trend of Lower gastrointestinal Endoscopy in Patients with Inflammatory Bowel Diseases: A Nationwide Population-Based Study in South Korea

Abstract Background Endoscopy plays an essential role in the diagnosis and management of inflammatory bowel disease (IBD). Although the interval of endoscopy is important to assess the disease status of IBD, there are limited research date on the real-world use of endoscopy in patients with IBD. Therefore we aimed to evaluate the current status of lower gastrointestinal (GI) endoscopy in IBD patients. Methods We conducted a nationwide, retrospective, observational cohort study using the Korean national health insurance claims data. The endoscopy cohort with IBD was defined as an IBD population who underwent at least one colonoscopy or sigmoidoscopy between 2010 and 2019. We evaluated the annual number of lower GI endoscopy use, including colonoscopy and sigmoidoscopy in the IBD prevalent patients. In addition, we analyzed the trend of endoscopy use stratified by year after diagnosis in the patients with newly diagnosed IBD between 2010 and 2017 and the logistic regression modeling was used to estimate odds ratios and 95% confidence intervals for endoscopy, compared with never having had endoscopy, by demographic factor and therapeutic medications used for IBD. Results The analysis included 54,634 IBD patients (34,633 male and 20,001 female), among whom 24,577 (44.94%) underwent lower GI endoscopy. During a mean follow-up of 4 years, endoscopy was performed the most in the first year after diagnosis, and it showed a decreasing trend after that. Multivariate analysis showed that IBD patients with biologics and small molecules received more endoscopy than patients without the medication (hazard ratio [HR] 27.671, 95% confidence interval [CI] 11.296–67.783). In Crohn’s disease, increased number of biologics and small molecules correlated with increased number of endoscopy (HR 1.049, 95% CI 0.981–1.122 for single biologic; HR 2.343, 95% CI 1.726–3.182 for two or more biologics). In ulcerative colitis, however, only the use of biologics and small molecules, not the number of medication, correlated with increased number of endoscopy (HR 23.26, 95% CI 9.489–57.02). IBD patients with steroid (HR 1.562, 95% CI 1.509–1.61) and 5-aminosalicylic acid (HR 1.622, 95% CI 1.537–1.711) were received more endoscopy than patients without the medication. Conclusion Endoscopy was performed more frequently in the first one year after diagnosis with IBD. Also, this study demonstrated significant association between the use of endoscopy and the biologics/small molecules administered for IBD.

N04 A systematic review of the impact of Inflammatory Bowel Disease (IBD) on family members

Abstract Background and Aims Inflammatory Bowel Disease (IBD) impacts the individuals’ quality of life and affects all family members considerably. Previous reviews have focused on the impact of IBD on the patient, with limited exploration of the impact of IBD on family members. Therefore, this review aims to synthesise existing knowledge on the impact of IBD on family members, their coping strategies, the support needed, and interventions for family members to prevent and alleviate the burden of IBD. Methods A systematic review using the mixed-method systematic review approach suggested by Joanna Briggs Institute (JBI) and the Preferred Reporting Items for Systematic Reviews (PRISMA) was undertaken. A systematic search of six bibliographic databases: MEDLINE, EMBASE, PsycINFO, CINAHL, British Nursing Index, and Web of Science, was performed in February 2021. The search focused on the impact of IBD on family members and coping strategies and interventions for this population. A narrative synthesis was conducted. Results In total, 3,258 records were identified, from which 33 relevant papers (2,748 participants) were included in the review, with case-control, cross-sectional, and qualitative designs. Synthesis of these papers found three themes: the impact of IBD on family members; the coping strategies for family members to overcome the negative impact of IBD; and the support needed. The IBD affects the family members in term of emotional well-being, fear and concern, relationship and social life, work and financial impacts, and leisure time and travelling. The coping strategy theme shows that family members use adaptive coping patterns such as acceptance, resilience, and emotional support from others. Maladaptive coping patterns such as denial following the initial relief of diagnosis, self-distraction, and self-blame were also used. In the theme ‘support needed’, family members reported the need for improved information about IBD, social support groups, self-help groups, educational meetings, and providing easy access to a counsellor or psychologist to support family members. There have been no studies assessing outcomes of interventions to relieve family members’ burden in the IBD population. Conclusion Our findings suggest that policymakers in healthcare services should emphasise the multidisciplinary professional care model such as a family therapist, IBD nurse, and psychologist. Researchers could incorporate a bio-psycho-social approach into their work on IBD to improve quality of life of both patients and their family members.

P399 C-Reactive Protein Values After Surgery for Inflammatory Bowel Disease: Is It Still A Good Marker For Intra-Abdominal Complication? A Retrospective Cohort Study of, 347 procedures

Abstract Background C-reactive protein (CRP) is a useful predictive test to early detect abdominal complication after colorectal surgery. Inflammatory bowel disease (IBD) is responsible of chronic inflammation and abnormal basal CRP that could influence the interest of its management after abdominal surgery. The aim of this study was to evaluate CRP as an indicator of postoperative complication in a specific IBD population. Methods Retrospective study of patients undergoing ileocolic resection or ileal pouch-anal anastomosis for IBD between, 2012 and 2019. Intra-abdominal complication was defined as any intra-abdominal event, infectious or otherwise, occurring during the immediate postoperative period. The early postoperative period was defined as post-operative days (POD), 1 and, 2 and late postoperative period as POD, 3 and 4. Results Ileocolic resection represented, 242 patients and ileal pouch-anal anastomosis, 105 patients. Intra-abdominal complications occured in, 18.1% of patients (ICR=40, 16.5% and IPAA=23, 21.9%). Pre-operative CRP (48 hours before surgery) was available for, 96 patients (29.8%). Among them, 64 had an abnormal CRP value (median:, 13±45.4). No relation was found between a preoperative abnormal CRP value and post-operative intra-abdominal complications. CRP was significantly higher at an early (105.2±56.0 vs, 128.1±69.8; p=0.008) and late stage (112.9±72.8 vs, 185.3±111.5; p &amp;lt;, 0.0001) for patients having an intra-abdominal complication. The best sensitivity and specificity values were obtained at POD, 3–4 with a CRP cut-off of, 75 with an area under the curve of, 0.71. The ability to rule out an intra-abdominal complication with a CRP Value &amp;lt;75 mg/L was good with, at POD, 1–2 NPV=86.4% and PPV=19.9% and, at POD, 3 an NPV=90.3% and PPV=22.2%. A BMI &amp;gt;25kg/m2 (p=0.04) and an open surgical approach (p=0.009) were associated with higher CRP levels in the first POD. In multivariate analysis, pre-operative steroid use (p=0.03), CRP at POD, 3 &amp;gt;, 100mg/L (p=0.002) and a rise between CRP values more than, 50 mg/L (p=0.005) or, 100 mg/L (p &amp;lt;, 0.0001) at, 48 hours were significantly associated with intra-abdominal complication. A CRP at POD, 1 &amp;lt;75mg/L was associated with a lower rate of intra-abdominal complication (p=0.01). A score using these, 4 independent factors was created and showed significant differences in intra-abdominal complication, anastomotic leakage and readmission rate. Conclusion CRP is a useful predictive marker to detect abdominal complication after surgery in IBD population. Measurement of CRP can help to reduce hospitalization stay and orientate towards complementary examinations.

P438 The Efficacy and Safety of ustekinumab Therapy in refractory Inflammatory Bowel Disease (IBD) patients with co-morbidities and old age

Abstract Background Ustekinumab is approved for treatment of active Crohn’s Disease (CD) and Ulcerative Colitis (UC) with a more favourable safety profile to anti-TNF therapy however it is still used with caution in the elderly and those with comorbidities. We present our data on safety and efficacy of Ustekinumab in our IBD population including consideration of age and existing medical conditions. Methods Clinical data on all IBD patients treated with Ustekinumab within our population between, 2016 and, 2021 were retrospectively collected from electronic records. This included baseline characteristics, diagnosis, previous medical and surgical history, comorbidities, clinical response, endoscopic response and adverse events (AEs). Results 120 (M=57, F=63) patients were identified, 98 CD, 17 UC and, 5 IBDU with a median follow up of, 13.9 months (IQR, 3–20.5) The median age of starting Ustekinumab was, 35.5 years (16–81) with, 65% (78/120) previously treated with two or more biologics suggestive of refractory disease. Clinical response was achieved in, 18.0% (16/89) of patients at, 8 weeks, 39.3% (24/61) at, 24 weeks, 42.0% (21/50) at, 1 year and endoscopic response and/or with imaging was seen in, 9/23 (39.1%) at, 24 weeks and, 3/18 (16.7%) at, 1 year. 10% (14/120) were &amp;gt;60 at time of starting Ustekinumab, this group had an average of, 1.4 comorbidities compared to, 0.3 in the &amp;lt;, 60 group (p value -0.00001), 7% (8/, 120) patients had had a prior malignancy (Non-melanoma Skin Ca, 4, Solid organ, 2, melanoma, 1, haematological, 1) and, 5 of these were in the &amp;gt;60 group with a median of, 10 years (IQR, 5–11) since being cured and no episodes of recurrence, with, 1 patient developing a malignancy post Ustekinumab. Adverse events (AEs) were seen in, 5.8% (7/120) of patients and a serious adverse event (SAE) in, 5% (6/120), this included, 4 patients in the &amp;lt;60 age group requiring admission for Intravenous antibiotics vs, 1 in the &amp;gt;, 60 age group (p value, 0.57). Conclusion This study contributes to the real-world data being presented regarding Ustekinumab. The efficacy demonstrated in clinical response is comparable to previous studies, the majority of patients having already been treated with two or more biologics. We have demonstrated a favourable safety profile in the over, 60 age group who had a greater number of comorbidities and a higher rate of previous malignancy. With an ageing IBD population the safety and efficacy of Biologics in the older age groups need to be further examined.

P588 T cell response to SARS-CoV-2 mRNA vaccines by an interferon-gamma release immunoassay in patients with Inflammatory Bowel disease receiving anti-TNF and thiopurine treatment

BackgroundTreatment with anti-TNF agents and thiopurines has been associated with an impaired immune response to some vaccines. SARS-CoV-2 vaccination is very effective in healthy individuals, but studies in inflammatory bowel disease (IBD) populations are scarce, especially regarding T cell response. We aimed to evaluate the T cell and antibody response in a cohort of IBD patients on anti-TNF and thiopurine treatment who received two doses of the SARS-CoV2 mRNA vaccine.MethodsAn observational, prospective study was carried out at our IBD clinic. We included Crohn’s disease (CD) and Ulcerative colitis (UC) patients receiving anti-TNF as monotherapy or anti-TNF + thiopurine (combo) or thiopurines only for at least six months at inclusion. Blood samples were drawn for interferon-gamma release assay (IGRA) and antibody determination six (+/- 2) weeks after the second vaccine dose. The specific T cell response to SARS-CoV-2 was determined by IGRA using Qiagen® QuantiFERON® SARS-CoV-2 RUO tubes with a patented Spike protein combination. Interferon-gamma was measured by CLIA using the LIAISON® QuantiFERON-®TB Gold Plus assay. As there is no validated cut-off point, we used those obtained in a cohort of 20 healthy health professionals published by our group (doi.org/10.1016/j.medcli.2021.09.013). Antibodies to the Spike (S) SARS-CoV-2 protein were analyzed by CLIA. Adverse events (AEs) and clinical activity were recorded.ResultsWe recruited 148 IBD patients, 57 treated with anti-TNF monotherapy, 53 with combo, and 38 with thiopurine only. Seventy percent had CD, and 60% were male. Using the cut-off value of the cohort mentioned above, the T-cell response was positive in 92% of anti-TNF monotherapy, 83% in combo, and 87% of the thiopurine group (p=ns). The anti-S antibodies were positive in 100% of our cohort. There were no changes in disease activity rates after the second vaccination, nor were severe AEs detected.ConclusionSARS-CoV-2 mRNA vaccination was very effective in IBD patients receiving anti-TNF (combo or monotherapy) or thiopurine treatment as measured by both T cell and antibody response. IGRA-specific tests may constitute a valuable tool in assessing cellular immunity in immunocompromised patients.

P222 Raman Spectroscopy in the diagnosis of pIBD: experimental study

Abstract Background Diagnostic delay is a major issue among the paediatric Inflammatory Bowel Disease (pIBD) population because of the association with higher risk of complications and growth failure. At present, non-invasive serological and faecal biomarkers lack sufficient sensibility and/or sensitivity to be used as a diagnostic tool in clinical practice and none can discriminate between Crohn’s Disease (CD) and Ulcerative Colitis (UC). In this setting, new non-invasive diagnostic tools with better diagnostic performance are needed.Raman Spectroscopy (RS) is a spectroscopic technique that relies on the inelastic scattering process of monochromatic light. Through the analysis of spectra molecular changes can be identified.The overall objective of this study was to explore RS performance as a non-invasive diagnostic test in IBD diagnosis. Methods RS was applied to the analysis of stool protein extracts in pIBD patients and a control group. Being directly in contact with the intestine stool can provide information on the bacterial and inflammatory background and represents an excellent sample material to study. At our Paediatric Gastroenterology Unit 55 patients (age 0–18) were enrolled, 32 cases (20 MC, 2 Very Early Onset-IBD, 9 CU, 2014 Porto criteria), 23 controls (functional constipation, irritable bowel syndrome, Rome IV criteria). Protein extract from faecal samples (obtained by the same kit test used to evaluate faecal calprotectin) were analysed with a DXR- Smart Raman Spectrometer (thermos Fisher Scientific, Waltham, MA, USA) with a 785 nm diode laser. After obtaining a spectrum the analysis focused on the band in the wavenumber range of about 1550–1750 cm-1 which defines the amide-I vibration modes, deconvolution of this band was performed. Ratio of the area of the sub-bands, parameter R, was calculated. Receiver Operating Characteristic (ROC) Curve and Youden Index (J) were used for statistical analysis. Results As represented by the ROC curve R showed a great diagnostic accuracy in differentiating between cases and controls, AUC 0,9389 (0,87-1,00) figure 1. A cut-off value of 1,2 distinguished cases from controls with sensibility 0,9 (0,78-0,95), specificity 1 (0,85-1), figure 2. In the group of cases R distinguished CD from UC, AUC 0,83 (0,65-1) figure 3. A cut of value of 1,4 distinguished CD from UC with sensibility 1 (0,69-1), specificity 0,83 (0,58-0,96) figure 4. Conclusion This is the first application of RS as a non-invasive diagnostic tool on stool samples. Preliminary data show that RS may recognize IBD from non-IBD features, and, what is completely new, it can discriminate the two main forms of IBD, CD and UC. Future prospective studies including patients with suspected IBD will help defining the diagnostic performance.

P653 The changing epidemiology of IBD in the western world: a population-based study from Denmark

Abstract Background Mitigating the burden of inflammatory bowel disease (IBD) in Western countries requires understanding how its epidemiology is evolving. We conducted a temporal analysis of the epidemiology of IBD between 1995 and 2018 in the Danish nationwide cohort. Methods We used the Danish Civil Registration System (CRS) to obtain demographic information on all residents in Denmark between January 1, 1995 and December 31, 2018. We obtained information on Crohn’s disease (CD) and ulcerative colitis (UC) diagnosis from the National Patient Registry (NPR) using International Classification of Disease 8/10 codes. IBD diagnosis was defined as having at least two CD- or UC-related registrations within a two-year period and the date of the first IBD-related registration was considered as the date of diagnosis. We estimated overall and annual incidence rates and prevalence of CD and UC standardized with respect to age and sex. Results 52,407 individuals met the criteria for IBD diagnosis in the period 1995–2018, of which 17,355 (33%) were diagnosed with CD and 35,052 (67%) were diagnosed with UC. The median age at diagnosis (IQR) for CD and UC was 34 (22, 53) and 43 (29, 60) years, respectively. 9,745 (56.2%) and 18,332 (52.3%) individuals with CD and UC, respectively, were of female sex. During the study period, 1995–2018, the overall incidence rate (95% CI) rose from 9.2 (8.4, 10) per 100,000 person years (PY) to 18 (16.8, 19) per 100,000 PY for CD, corresponding to a 94.9% increase, and from 21.1 (19.9, 22.4) per 100,000 PY to 28.4 (27, 29.8) per 100,000 PY for UC, corresponding to a 34.1% increase. The incidence rates of CD and UC increased for all age groups, at different rates, highest for CD in age group 15–39 years (Figure). While CD incidence was consistently higher in women, increase in CD and UC incidence was comparable between both sexes. The prevalence of IBD also increased from 1995–2018 (225.6% and 218.4% for CD and UC, respectively) with the greatest increase in UC prevalence among individuals older than 40 years of age (248.4%). Conclusion The epidemiology of IBD has shifted in the last 20 years with a still increasing incidence of CD and UC in young adults, and a sharply increased prevalence in older age groups, especially for UC. These findings have implications towards understanding environmental shifts associated with this evolution as well as preparing for management of an aging IBD population.

DOP72 The association of anti-tumor necrosis factor and thiopurine therapy with the risk of lymphoma among Inflammatory Bowel Disease patients: A nation-wide study from the epi-IIRN

Abstract Background To clarify the risk of lymphoma in patients with inflammatory bowel diseases (IBD) exposed to anti-tumor necrosis factor (anti-TNF) and/or thiopurines we aimed to evaluate the Israeli IBD population. Methods A nested case-control study on the epidemiology cohort of the Israeli IBD Research Nucleus (epi-IIRN) including all 4 Health Maintenance Organizations in Israel linked to the Israeli Cancer Registry. Patients diagnosed since 1.1.2005 until 31.12.2015 (42,954 patients) were included and followed until 31.12.2017. Each lymphoma case was matched to 30 non-lymphoma IBD patients by age, gender, IBD subtype, and date of earliest evidence of IBD in the database. Patients with other risk factors for lymphoma, or lymphoma diagnosis prior to IBD diagnosis were excluded (figure 1). Conditional logistic regression was used to compute the association of drug exposure (anti-TNF, thiopurines and combination) with diagnosis of lymphoma. Patients without exposure to anti-TNF and/or thiopurines in each group served as reference within each group. Additionally, sub-group analyses by gender, age group at inclusion (≤48, 49–64, ≥65), time from last drug exposure (≤90 days, 91–365 days, &amp;gt;365 days) were done. Results The final nested cohort included 5556 IBD patients (185 lymphoma cases matched to 5,371 without lymphoma). Mean follow-up (F/U): 5.5±3.5 years, 50% with Crohn’s disease, mean age at database entry 52.6±17.80 years. Anti-TNF-only exposure was documented in 4.3% (8/185) of lymphoma cases vs. 2.6% (145/5,371) of controls OR 1.97, CI 0.93–4.16, p=0.07; in males the ORs were 2.84 (CI 1.17–6.92 p=0.04) and increased to OR 3.48 (CI 1.55–7.88, p=0.002) for males &amp;lt;48 years and OR 2.87 (CI 1.53–5.37, p=0.001) for patients with last exposure ≤90 days (figure 2). Exposure to combination anti-TNF+thiopurines occurred in 8.6% (16/185) of lymphoma cases vs. 5.3% (282/5,371) of controls OR 2.09 (CI 1.17–3.73, p=0.013). Males on anti-TNF-thiopurine combination had OR of 3.42 (CI 1.37–8.52, p=0.003) and in sequential (non-overlapping exposure to both thiopurines and anti-TNFs during F/U) combination an OR of 2.74 (CI 1.02–7.35 p=0.02). Thiopurine-only exposure occurred in 15.1% (28/185) of lymphoma cases vs. 13.5% (726/5,371) of controls, OR 1.32 (CI 0.86–2.03, p=0.20). Males on thiopurines had an OR of 1.75 (CI 1.02–2.99, p=0.05). The risk increased further in males &amp;lt;48 years OR 2.17 (CI 1.01–4.66, p=0.047) and in males aged≥65 OR 3.50 (CI 1.55–7.82, p=0.002). Females were not at risk for lymphoma (figure 3). Conclusion This nationwide study suggests that exposure to anti-TNF therapy alone or in combination with thiopurines may be associated with an increased risk of lymphoma, but only in males, especially when last exposure occurred within 90 days.

DOP21 Potential mechanisms linking biological therapies on SARS-CoV-2 susceptibility in Inflammatory Bowel Disease patients

BackgroundThe current novel coronavirus (SARS-CoV-2) pandemic is an ongoing global health crisis, which represents an important challenge for the whole society and mankind. Patients with inflammatory bowel disease (IBD) are treated with immunosuppressive drugs that are usually associated with more severe viral infections. However, the effects of the different therapies on the risk of SARS-CoV-2 infection and Covid-19 severity in IBD patients are still under investigation.MethodsBetween April 2020 and April 2021, 238 IBD patients (N=145 with Crohn disease and N=93 with Ulcerative colitis) of the North Italy area have been enrolled. Both serum samples (N=238 IBD patients and N=45 healthy donors) and colon biopsies from inflamed and non-inflamed mucosa (N=88 IBD patients N=20 non-IBD control) have been collected. To evaluate the exposure to SARS-CoV-2, both clinical data and seroprevalence of anti-SARS-CoV-2 Ab have been analyzed. Serum samples were analyzed by untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD versus healthy donors. Moreover, gene expression analysis of key proteins for virus entry (ACE2, TMPRSS2, TMPRSS4, ADAM17) were analyzed by qPCR in the gut mucosa biopsies of IBD patients.ResultsThe seroprevalence of anti-SARS-CoV-2 Ab in our cohort of IBD patients (10/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Accordingly, we observed that the serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), than healthy controls (N=45, 50%). Gene expression analysis of the proteins involved in SARS-CoV-2 entry also indicated that IBD patients treated with anti-TNF (N=14) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=7) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar.ConclusionOur study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection. Future studies to gather the mechanisms underpinning the effects of biologics on the expression of the proteins involved in SARS-CoV-2 viral entry in association with the specific metabolomics signature of viral susceptibility might shed light on potential targets to increase resistance in higher risk subgroups of patients.

P318 Safety of Biological Therapies in Elderly IBD: a Systematic Review and Meta-analysis

Abstract Background There was a significant progress in the medical therapy of inflammatory bowel diseases(IBD) with the advent of biological compounds, yet patients may experience adverse events(AE): infusion/injection reactions, infections and malignancies, understudied in vulnerable patient populations (e.g. elderly). Methods We systematically searched PubMed/Medline and conferences proceedings between January, 1, 2010, and June, 1, 2021, to identify eligible studies that examined the safety of biologic therapies in elderly patients with IBD. Two reviewers independently evaluated the collected studies based on inclusion and exclusion criteria. Search was focused on MESH Terms including IBD/CD/UC, biological therapy, adverse events, infections, infusion/injection reaction and malignancy and elderly. Results Our search identified, 2885 articles and, 12 congress abstracts trough the data base search, finally, 14 peer reviewed papers and, 3 abstracts met the inclusion criteria. Most studies were retrospective, merging CD and UC patients, with an age limit of, 60 or, 65 years for elderly, from Europe or North America. According to our meta-analysis the rates of AE were not different according to the type of biologics (mean rate:, 11.3 (CI, 95%, 9.9–12.7)/100 pts years; p=0.11) in elderly IBD patients with the use of anti-TNF, vedolizumab(VDZ) and ustekinumab(UST). Similarly, rates of infection (mean rate:, 9.5 (CI, 95%, 8.4–10.6)/100 pts years; p=0.56). On the other hand, regarding infusion/injection rates were more common in patients on anti-TNFs (mean rate:, 2.51 (CI, 95%, 1.7–3.4/100 pts years; p=0.02) and malignancy rates were higher in elderly patients on VDZ/UST (mean rate:, 2.14 (CI, 95%, 1.6–2.8)/100 pts years; p=0.01). Two studies directly comparing anti-TNF and VDZ reported similar efficacy and safety in the elderly IBD population. (p=0.56; Total: reflects patient year of follow-up.) Conclusion We report the first meta-analysis on the comparative safety of biological therapies in elderly IBD patients. Rates of adverse events and infections were not different across the biologics. In contrast, infusion/injection reactions were more common in patients on anti-TNFs. Current data are insufficient to suggest sequencing among biologicals in the elderly based on the safety, larger studies in elderly IBD population are warranted.

P283 Infliximab re-challenge: could it be an option in refractory IBD patients?

Abstract Background Infliximab (IFX) is effective in treatment of inflammatory bowel disease (IBD). However, primary non-response and secondary loss-of-response rates go up to 30–40% and intolerance may occur leading to treatment switch. Unfortunately, even with increased availability of new molecules, some patients remain refractory to all currently available medical options. This study assesses the effect of IFX re-challenge in a real-life cohort of highly refractory IBD patients. Methods A retrospective observational study was set up to analyse the effect of IFX rechallenge in IBD patients previously treated with IFX and found refractory to other biologics. Cases between August 2018 and June 2021 with at least one year of follow-up (FU) were analysed. Clinical, biological (CRP and faecal calprotectin [FC]) and endoscopic response was evaluated, as well as adverse events (AE). Results Ten patients with refractory IBD were included (9 Crohn’s disease [CD], 1 ulcerative colitis [UC]). Details on previous treatment before IFX re-challenge are shown in Table 1. All patients had active disease at the start of IFX re-challenge. Median baseline CRP was 12.6mg/L [4.9–24.1] and FC 396mg/kg [64–2786.8]. IFX was started in combination with systemic steroids, immunosuppressants and ustekinumab in 50%, 70% and 10% of patients, respectively. Baseline endoscopy showed severe active disease in 7/8 patients. Clinical and endoscopic response rates are shown in Table 2. Biological response is shown in Figure 1. After 1 year FU, all (7/7) required intensified dosing (4-weekly), in 3/7 corticosteroid free clinical remission was reached. IFX re-challenge was discontinued after the second administration in 2/10, due to a severe allergic reaction despite premedication with antihistamines and corticosteroids (1 anaphylactic shock admitted to intensive care unit, fully recovered). IFX was continued in 8/10. Other AE (not in all cases considered to be related to IFX) included: disease flare-up requiring hospitalization (3/10), liver test abnormalities (1/10), new perianal abcedation (1/10), subobstruction (1/10), C. difficile infection (1/10), EBV infection (1/10) and Addison crisis (1/10). Conclusion IFX re-challenge was efficient in inducing clinical and endoscopic response in this highly refractory IBD population. However, there is a non-negligible risk of AE including infusion reaction.

N18 Introduction of inflammatory bowel disease specialized dietitian and nutritional status in a multidisciplinary IBD team

Abstract Background Qualitative inflammatory bowel disease (IBD) care is marked by a multidisciplinary approach including physicians, nurses, psychologists and dietitians. Specialist IBD dietitians can address the specific needs of patients with IBD, with an emphasis on nutritional status, disease activity, and functional symptoms. We wanted to obtain a snapshot of the IBD population referred to the dietitian at our IBD clinic. Methods Since February 2021, two specialist IBD dietitians were hired at the multidisciplinary IBD-team of our tertiary referral centre. Data from all IBD patients seen by the IBD-dietitians were prospectively collected. Patients with IBD were referred to the IBD dietitians for dietary advice concerning optimization of nutritional status, modulation of diet-induced abdominal symptoms, and IBD-related problems (e.g. high output stoma, obstruction, enteral or parenteral nutrition). Malnutrition as reason for referral was defined as an abnormal body mass index (BMI &amp;lt;18.5 or &amp;gt;25 kg/m²). Results From 1 February 2021 until 16 November 2021, 219 IBD patients (58.4% women, median age 38 years, 127 Crohn’s disease, 92 ulcerative colitis) were seen by the IBD-dietitians. Patient characteristics are described in table 1. A total of 303 contacts were registered, including 82% in-hospital consultations (16% in-patient clinic, 66% outpatient clinic) and 18% remote consultations (via telephone or email). The median BMI at first consultation was 23.49 kg/m2. In this cohort, 46.6% of IBD patients had a normal BMI, 37% were obese or overweight, and 13.2% has underweight. Males had a significantly higher BMI than females (BMI 24.5 vs 22.5 kg/m2, p-value 0.048). The main reasons for referral were IBD-related symptoms or disease activity (46.6%), malnutrition (26%), functional symptoms (16.4%), and patient’s interest in receiving more information on diet (9%). Of note, none of the patients were being treated with enteral nutrition at time of referral, and only 5 patients were being treated with parenteral nutrition. Most patients received dietary advice (92%) and only 1 patient was started with enteral nutrition. Conclusion The introduction of IBD-dietitians in our multidisciplinary IBD care program has allowed IBD-patients with or without malnutrition, to be assessed by a specialist IBD dietitian who can provide appropriate dietary advice. Of note was that despite an already expert IBD center with a multidisciplinary team in place, the prevalence of malnutrition in this selected IBD cohort was very high. Nevertheless, IBD disease activity and IBD-related symptoms were the main reason for referral to the IBD-dietitian, reflecting the need for tailored nutritional advice complementary to medical or surgical treatment.

P451 Evaluating drug sustainability, efficacy and safety of biologic agents in elderly patients with Inflammatory Bowel Disease: a single center retrospective study

Abstract Background Despite the advancement in pharmacological management of Inflammatory Bowel Disease (IBD), the efficacy and the side effects of the biologics are rarely studied in the elderly population. Our aim was to evaluate retrospectively the drug sustainability, efficacy, and safety of the biologic therapies in the elderly IBD population. Methods Consecutive elderly (&amp;gt; 60 years old) IBD patients, treated with biologics (infliximab, adalimumab, vedolizumab, ustekinumab) followed at the McGill University IBD Center were included between January 2000 and 2020. The efficacy of treatment was measured using clinical and biochemical parameters. Response and remission variables were measured at three distinct time points from the start date of the biologic agent, as in 3, 6–9 and 12–18 months. Patients required a minimal follow-up period of three months. Adverse events (AE) or serious adverse events (SAE) occurring within three months of the last biologic dose were considered to be related to the biologic agent. Results We identified a total of 147 elderly patients with IBD treated with biologic agents (109 Crohn’s disease (CD) and 38 ulcerative colitis (UC)). Disease location was predominantly ileocolonic (47.7%) in CD and pancolitis(63.2%) in UC. 47.6% of elderly IBD patients had attempted at least 1 biologic agent (Table1). The mean duration of biologic treatment was 157.5 (SD:148)weeks. Steroid exposure varied from 34% at the start of biologic therapy to 19% at 3 months, 16.3% at 6–9 months and 6.5% at 12–18 months.’ The remission rates at 3, 6–9 and 12–18 month were not significant between the biologic therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability (p=0.195)(Figure1), time to adverse event (p=0.158) (Figure2) or infection rates (p=0.973) (Figure3) between all four biologics studied. The most common AEs led to discontinuation were loss of response, infusion or injection reaction and infection. Conclusion Current biologic therapies were not different with regards to drug sustainability and safety in the elderly IBD population. Based on these results, we are not able to suggest a preferred sequencing order among biologicals.