Abstract Background Ulcerative Colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Current therapeutic goals emphasize clinical and endoscopic remission; however, histological remission has emerged as an important target due to its association with reduced relapse rates and improved long-term outcomes. Despite this, limited data exist on the concordance of histological activity between colonic segments, especially in UC patients in clinical remission. This study investigates the correlation between histological disease activity in the rectosigmoid colon (RSC) and other colonic segments in patients with UC in clinical remission. Methods This prospective study analyzed data from 203 UC patients in clinical remission, defined as a partial Mayo score ≤2 and rectal bleeding score = 0 for at least three months. Colonoscopies with segmental biopsies were performed, and histological activity was assessed using the Geboes score. Histological remission was defined as a Geboes score <2A.0, while active disease was classified as ≥3.1. Correlation between histological activity in the RSC and other colonic segments was evaluated using Spearman’s correlation coefficients and logistic regression. Statistical significance was defined as p < 0.05. Results Among the 203 patients, the median age was 45 years, with 55.1% having pancolitis. Histological activity in the RSC showed poor correlation with other colonic segments. In patients with a RSC Geboes score of ≥3.1, the correlation coefficient between the RSC and descending colon was 0.05 (p = 0.62), between the RSC and transverse colon was -0.03 (p = 0.71), and between the RSC and right colon was 0.12 (p = 0.09). In patients with a RSC Geboes score of <2A.0, the correlation coefficient between the RSC and descending colon was 0.12 (p = 0.22), between the RSC and transverse colon was 0.05 (p = 0.59), and between the RSC and right colon was 0.18 (p = 0.01). Even among patients with pancolitis, histological concordance between segments remained low. These findings underscore substantial segmental variability in histological activity. Conclusion Flexible sigmoidoscopy (FS) is commonly used to monitor UC due to its practicality; however, our findings suggest FS may not reliably reflect proximal histological disease. The lack of concordance highlights the limitations of FS in accurately assessing histological remission, including in patients with pancolitis or extensive colitis. Full colonoscopy with segmental biopsies remains the gold standard for comprehensive disease evaluation and management. Further research is warranted to refine histologic assessment strategies in UC.

Abstract Background Ustekinumab (UST) and vedolizumab (VED) have proven to be effective therapies for ulcerative colitis (UC), with similar safety profiles. There are limited real-world studies comparing the effectiveness between UST and VED in UC, especially after anti-TNF failure1–4. Our aim was to evaluate the real-world efficacy and safety of UST and VED in UC patients previously exposed to anti-TNF therapies across multiple Canadian institutions. Methods This was a multicentre retrospective study looking at 12 months of clinical data for patients with UC who had previously been exposed to at least one anti-TNF. These patients were from McGill University Health Centre, Hamilton Health Sciences, and London Health Sciences Centre. The primary outcome was clinical remission at 6 months, defined by a partial Mayo score (pMS) ≤ 2, Mayo Endoscopic Score (MES) ≤ 1, or physician’s judgement of clinical remission. Secondary outcomes included clinical remission at 12 months, clinical response, biochemical remission and response, and drug persistence at 12 months. Clinical response was defined as a decrease in pMS ≥ 2 points or physician’s judgement of clinical response. Biochemical remission was defined as c-reactive protein (CRP) < 5mg/L and/or fecal calprotectin (FCP) < 250μg/g. Biochemical response was defined as a reduction of CRP or FCP by 50% from baseline. These parameters were all evaluated at 6 and 12 months. Adverse events were summarized for all patients after 12 months. Results One hundred and fifty patients were included: 28 in UST and 122 in VED. Mean age was 38.4 (SD 15.6) in UST and 43.8 (SD 16.8) in VED. Percentage of female patients was 67.9% in UST and 53.3% in VED. Mean baseline partial mayo score was 3.78 (SD 3.07) for UST and 4.48 (SD 2.43) for VED. Mean disease duration was 10.63 years (SD 8.44) for UST and 11.80 years (SD 8.25) for VED. There was no significant difference in clinical remission between UST or VED, for data that was available at each time point (UST 65.0% vs. VED 72.6%, p=0.49 at 6 months; UST 68.4% vs. VED 82.3%, p=0.17 at 12 months). There was no significant difference between UST and VED for biochemical remission at 6 and 12 months. Higher MES at baseline was negatively associated with clinical remission in UST and VED with univariate analysis, though only significant in VED when adjusted for sex, age, and disease duration (OR 0.07, 95% CI [0-0.26], p=0.0006). There was no significant difference between drug persistence at 12 months (95.0% UST vs. 91.5% VED, p=0.41). Infectious adverse events were similar between groups (17.9% UST vs. 4.1% VED, p=0.07), with no serious adverse events. Conclusion This real-world multicentre Canadian study shows similar efficacy and safety profiles for UST and VED in UC over 1 year. References 1.Holvoet T, Truyens M, De Galan C, et al. Safety and Effectiveness of Vedolizumab and Ustekinumab in Elderly Patients with Inflammatory Bowel Disease: A Real-Life Multicentric Cohort Study. J Clin Med. 2024;13(2). doi:10.3390/JCM13020365 2.Nomura K, Shibuya T, Odakura R, et al. Comparison of the Effectiveness of Vedolizumab and Ustekinumab in Patients with Ulcerative Colitis: A Real-World Retrospective Study. Biomedicines. 2024;12(9):1991. doi:10.3390/BIOMEDICINES12091991 3.Fumery M, Serrero M, Bouguen G, et al. Real-World Comparison of the Effectiveness between Ustekinumab and Vedolizumab in Patients with Ulcerative Colitis Exposed to at least One Anti-TNF Agent. J Crohns Colitis. 2024;18(10):1615-1621. doi:10.1093/ECCO-JCC/JJAE063 4.Meyer A, Fumery M, Peyrin-Biroulet L, et al. Comparative real-world effectiveness of vedolizumab and ustekinumab for patients with ulcerative colitis: a GETAID multicentre cohort study. Scand J Gastroenterol. 2022;57(12):1454-1462. doi:10.1080/00365521.2022.2095668

Abstract Background Endoscopic healing in patients with ulcerative colitis predicted higher rates of clinical remission at 12 months follow-up. Meanwhile, active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis was associated with relapse. [1] We aim to evaluate the impact of baseline endoscopic and histological healing on long-term clinical relapse as well as the rates of UC-related emergency room (ER) visits, hospitalizations and surgery. Methods This prospective observational study was conducted at the Inflammatory Bowel Disease (IBD) Centre of McGill University Health Centre (MUHC) July 2012 to July 2020 and included all adult UC patients undergoing a colonoscopy with biopsies for disease assessments. Patient must have been in clinical remission with a stable dose of medication for at least 3 months prior to enrolment. Patients were followed every 3 months in the first year then every 6-12 months to assess disease relapse, defined as a partial Mayo score (PMS) >2. Active endoscopic disease was defined as Mayo endoscopic score (MES) of 2 or 3. Active histological disease was defined as a Geboes score ≥3.1 (epithelial neutrophils with or without crypt destruction/erosions). Results A total of 253 patients were included in this study. At the 3-year follow-up, baseline active endoscopic and histological disease did not predict clinical relapse. However, baseline endoscopy with a EMS of 0 (compared to 1-3) showed a trend towards significance in predicting relapse (P = 0.08). Multivariate analysis adjusting for age, gender, height, and smoking status remained non-significant (P = 0.0837, 95% CI 0.29–1.08). At 5 years, baseline histological activity did not predict risk of clinical relapse, however, endoscopy with EMS 0 significantly predicted clinical relapse (P = 0.0080), with multivariate analysis confirming this (P = 0.0110, 95% CI 0.27–0.84). Baseline endoscopy with EMS 1-3 was linked to increased ER visits at 3 years (P = 0.02), but not at 5 years (P = 0.7618). Histological disease activity was not linked to increased ER visits at 3 and 5 years. Neither baseline endoscopy nor histology predicted the risk of hospitalisation or surgery at either follow-up (P > 0.05). Conclusion Active histologic disease did not predict long-term clinical relapse at 3- or 5-years point. On the other hand, baseline endoscopic activity of EMS of 0 compared to 1-3, only predicted clinical relapse at 5 years and IBD-related ER visits at 3 years. This long-term follow up data questions the additional role of histology in patient with complete endoscopic healing. References 1.Bessissow T, Kron CM, Marcus V, Lemieux C, Laneuville J, Afif W, Wild G, Lakatos PL, Brassard P, Bitton A. Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis. Am J Gastroenterol. 2022 Oct 1;117(10):1632-1638. doi: 10.14309/ajg.0000000000001912. Epub 2022 Jul 21. PMID: 35862833.

Abstract Background Patients with IBD are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD) due to chronic inflammation, hepatotoxic drugs, alteration of gut microbiota. MASLD, formerly known as non-alcoholic fatty liver disease, provides a positive rather than negative diagnosis, appropriately assigns a metabolic basis for hepatic steatosis (HS), avoids any potentially stigmatizing term, and excludes alcohol abuse. MASLD carries higher risk of both liver fibrosis progression and extra-hepatic involvement, including cardiovascular disease , extra-hepatic cancer, hypothyroidism, chronic kidney disease (CKD). Data on the effect of MASLD on fibrosis progression and multi-organ co-morbidities are lacking in this population. Aims We aimed to determine if MASLD and liver fibrosis carry a higher risk of extra-hepatic co-morbidities in IBD. Methods We prospectively included consecutive IBD patients who underwent liver stiffness measurement (LSM) with controlled attenuation parameter (CAP) by Fibroscan at a single centre. MASLD was defined as any grade HS without alcohol abuse and viral hepatitis. HS progression was defined as any grade HS (CAPampersand:003E270 dB/m), or transition to severe HS (CAPampersand:003E330 dB/m) with CAPampersand:003E270 but ampersand:003C330 dB/m at baseline. Fibrosis progression was defined as significant liver fibrosis (LSM≥8 kPa), or transition to cirrhosis (LSM≥13 kPa) with LSMampersand:003E8 but ampersand:003C13 kPa at baseline. We estimated incidence rates of HS and fibrosis progression by dividing participants with the outcome by number of person-years (PY) of follow-up. Covariate adjustments for HS progression were evaluated by multivariable Cox regression models and predictors of extra-hepatic conditions by multivariable logistic regression analysis. Results 430 patients were included with mean age 43 years, BMI 25 Kg/m2, IBD duration 14 years, CRP 5.2, ALT 22; females 45%, ulcerative colitis (UC) 31.8%, T2DM 4.7%. Patients with MASLD had higher proportion of CV events (12% vs. 6%), CKD (8% vs. 3%) and hypothyroidism (12% vs. 6%) vs. those without. After adjusting for age, male sex and Crohn’s IBD subtype, MASLD remained an independent predictor of extra-hepatic comorbidities (aOR 1.79, 95% CI 1.15–2.78; p=0.01) with T2DM (aOR 3.53, 95% CI 1.68-7.42; p=0.001). Patients were followed for 26 months (SD 16.4). Rate of HS progression was 16.2 per 100 PY (95% CI, 11.5-22.8) and liver fibrosis progression was 6.12 per 100 PY (95% CI 3.48-10.44). In multivariable analysis, after adjusting for IBD duration and BMI,UC was associated with faster progression of HS (aHR 2.21, 95% CI 1.02-4.91). Conclusions MASLD is associated with extra-hepatic diseases in patients with IBD and can progress to liver fibrosis and cirrhosis. Figure 1. Evolution of NAFLD and associated liver fibrosis in patients with IBD. Funding Agencies CIHR

Abstract Background Rectal bleeding and increased stool frequency are the most common symptoms patients with UC report, and they are key components in most of disease activity scores. It is unclear whether the severity of patient reported outcomes (rectal bleeding or diarrhea) correlate with endoscopic or histological disease activity. The aim of this prospective study is to evaluate the role of rectal bleeding and increased stool frequency as predictors for endoscopic and mucosal activity in patients with UC. Methods A single-center prospective observational study was conducted from July 2012 to July 2020. Adult patients aged 18 or older, with a confirmed UC diagnosis in clinical remission for at least 3 months, presenting to the endoscopy unit for disease activity evaluation or surveillance, were included. The partial Mayo score assessed rectal bleeding and stool frequency, considering scores of zero for each as clinical remission. Active endoscopic findings were defined by an endoscopic Mayo score > 1, and active histology was assessed using the Geboes score (active disease defined as Geboes score ≥ 3.1) from rectal biopsies. Logistic regression analysis and generalized estimated equation (GEE) were employed to evaluate the predictive impact of rectal bleeding and stool frequency at different time points on endoscopic and histologic disease activity at 12 months. Results The study enrolled 253 patients and the analysis revealed a significant association between rectal bleeding and stool frequency scores with 12-month endoscopic and histologic activity at different time points. Rectal bleeding at 9 months (OR: 7.64, 95% CI: 1.43 - 40.90, p = 0.0175) and 12 months (OR: 19.89, 95% CI: 3.98 - 99.52, p = 0.0003) showed a significant association with active endoscopic findings at 12 month in the multivariate analysis. At 12 months, the multivariate model of rectal bleeding revealed a significant association with active histology, with OR of 11.87 (95% CI: 1.26-112.03, p = 0.0307). On the other hand, stool frequency at 12 months exhibited significant associations with the 12 months endoscopic and histologic activity with OR of 7.31 (95% CI: 2.38 - 22.49, p = 0.0005) and OR of 13.02 (95% CI: 1.60-105.74, p = 0.0163), respectively. Conclusion Rectal bleeding and stool frequency scores are useful tools to predict endoscopic and histological activity in UC patients.

Abstract Background Upadacitinib is a selective JAK1 inhibitor that has recently been approved for treatment of moderate-severe Crohn’s disease, with Phase III clinical trials showing positive efficacy and safety profiles. Our aim was to evaluate the real-world experience of upadacitinib in a refractory cohort of Canadian patients with Crohn’s disease. Methods This was a two-centre retrospective study looking at 12-week induction data for patients with active Crohn’s disease from McGill University Health Centre and Hamilton Health Sciences. The primary outcome was clinical remission at 12 weeks, with secondary outcomes including clinical response, biochemical remission, and biochemical response. Clinical remission was defined as a Harvey-Bradshaw index (HBI) < 5. Clinical response was defined as an HBI reduction of ≥ 3. Biochemical remission was defined as a c-reactive protein (CRP) < 5 mg/L and/or fecal calprotectin (FCP) < 250 μg/g. Biochemical response was defined as a reduction of CRP or fecal calprotectin by 50% from baseline. These parameters were all evaluated at 8 and 12 weeks. Adverse events were summarized for patients who had follow up data available and included in the efficacy analysis. Results There were 28 patients who were treated in total, all of which had multiple biologic treatment failures. Baseline median age was 37, median HBI was 9, median CRP was 9.41 mg/L, and median FCP was 580 μg/g. The median disease duration was 13.5 years. Four patients discontinued upadacitinib due to no response or side effects. For all available data including patients who discontinued upadacitinib, clinical remission was achieved at 12 weeks in eight patients (8/11, 72.7%). Clinical response was achieved in eight patients (8/11, 72.7%), biochemical remission was achieved in four patients (4/11, 36.4%), and biochemical response was achieved in six patients (6/11, 54.6%). Of those that were initially on steroids (n=5), four patients (4/5, 80.0%) were able to wean off steroids and achieved a steroid-free clinical or biochemical response at 12 weeks. Of those who had previously been on off-label tofacitinib (n=5), clinical follow-up data was available for three patients at the end of the 12-week induction period. Two patients achieved clinical remission (2/3, 66.7%) and three patients had a clinical response (3/3, 100%). Among 13 patients with follow-up data, adverse events were observed in three patients (3/13, 23.1%), with two having non-serious infections (2/13, 15.4%) and one having fevers of unknown origin (1/13, 7.69%). Conclusion This real-world multicentre Canadian induction study shows favourable efficacy and tolerability of upadacitinib in refractory active Crohn’s disease.

Abstract Background Faecal calprotectin (FCP) is a reliable surrogate marker for disease activity in ulcerative colitis (UC). However, there are no consensus cut-off values for histoendoscopic remission. The aim of the study is to correlate FCP with Mayo Endoscopic Score (MES) and histological disease activity (Geboes score) of UC patients in clinical remission. Methods We performed a prospective study including adult UC patients at the McGill IBD Center between 2013 and 2017. Patients in clinical remission (partial Mayo score ≤2) or disease relapse, undergoing endoscopy for disease activity or dysplasia surveillance, were enrolled. Before bowel preparation, FCP was collected. MES was documented during colonoscopy. Biopsies were taken throughout the colon and histological activity was assessed using Geboes score (GS) by a blinded expert gastrointestinal pathologist. Results The study included 253 patients, of which 117 (46%) were male with a mean age of 38.2 years (standard deviation [SD] ± 24.8). 46% of the patients had pancolitis at the time of colonoscopy. 5-aminosalicylate were used by 68.4% of patients while 20.9% were on immunomodulators, 19% on biologics and 0.4% on small molecules as treatment. Regarding endoscopic correlation, it showed that an FCP ≥ 200 μg/g predicts MES > 1 despite clinical remission, yielding sensitivity of 59% and specificity of 74%. A FCP ≥ 123 predicts MES > 0 despite clinical remission (58% sensitivity and 70% specificity), also aiding to differentiate MES 0 from MES 1 (61% sensitivity and 70% specificity). As to histologic correlation, a FCP ≥ 80 μg/g identified histological disease activity using Geboes criteria (GS score > 3.1) in patients with clinical remission, yielding 64.7% sensitivity, 58.7% specificity and 77% positive predictive value (Figure 1). When using a GS score threshold of > 2, a cut-off value of FCP ≥ 50 μg/g, appears to be the most clinically relevant to identify patients in clinical remission who continue to have active histologic inflammation, with an 49.6% sensitivity, 41.6% specificity and 40% positive predict value. Results are summarized in Table 1. Conclusion FCP correlates very well with endoscopic and histologic disease activity and can be used as a surrogate marker for disease activity. Our study prospectively demonstrated the optimal cut-off values helping to discriminate endoscopic healing and histologic remission.

Abstract Background Current evidence suggests that biosimilar is safe and effective for patients with IBD. There is limited data on and nocebo effect after switching from originator to biosimilar. We aimed to report clinical efficacy, therapeutic drug monitoring, adverse events (AEs), and frequency of nocebo in IBD patients with biosimilar switches. Methods We performed a prospective observational study of 257 consecutive IBD patients who underwent biosimilar switch at McGill University Health Centre, Montreal, Canada, between November 2021 and October 2022. We excluded 74 patients due to missing follow-up data/delay in the switch. Patients underwent a mandatory switch from the originator (Remicade or Humira) to biosimilars due to a change of the reimbursement policy in Quebec. Clinical and biochemical data were captured at 8 weeks before switch, baseline (time of the switch), and 12 and 24 weeks after the switch. Clinical remission was defined as an HBI<5 for Crohn’s disease (CD) or a partial Mayo<3 points for ulcerative colitis (UC). Biomarkers remission was defined as C-reactive protein (CRP<5mg/mL) and fecal calprotectin (FCAL)<250 mcg/g. Drug trough levels and anti-drug antibodies were measured at baseline and week 24 (therapeutic level was defined as infliximab level≥3mcg/mL, adalimumab≥5mcg/mL). AEs and nocebo effects were assessed. Results A total of 183 patients were included [79.2% were CD, male 57.4%, median age at inclusion 46 years (IQR 30-52), and median duration of disease 13 years (IQR8-22)]. There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch(88.5%), baseline(93.8%), week 12(85.7%) and week 24(88.7%), p=0.835. Similarly, the proportion of patients remaining in biomarkers remission was not significantly different at week 8 before the switch, baseline, week 12 and week 24; CRP (82.4%/75.0%/80.0%/77.3%), p=0.760; FCAL (76.7%/77.8%/71.2/77.3%), p=0.932, as well as there was no significant difference in the proportion of patients maintaining the therapeutic level, (85.5%/82.2%/79.6%, p=0.853) and prevalence of positive anti-drug antibody at (10.5%/4.4%/11.8%, p=0.190) at 8 weeks before switch, baseline, and week 24, respectively. 14.5% of patients had subtherapeutic drug levels, 6% underwent dose optimization, and 4.4% had a loss of response/relapse. Nocebo was reported in 12% of patients (9.3% within the first 12 weeks and 2.7% within the first 24 weeks after the switch), 5.5% had drug AEs,and 3.8% discontinued biosimilars due to AEs. Conclusion Despite a significant number of early nocebo complaints within the first 3 months after the biosimilar switch, no significant changes were found in clinical efficacy, therapeutic drug trough level, and anti-drug antibodies.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. Both NAFLD and cardiovascular diseases seem more frequent in patients with inflammatory bowel disease (IBD). Purpose We aimed to assess the effect of NAFLD and associated liver fibrosis on the cardiovascular risk in people with IBD. Method We prospectively included IBD patients undergoing a routine screening program for NAFLD by transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD and significant liver fibrosis were defined as CAP >275 dB/m and liver stiffness measurement (LSM) by TE ≥8 kPa, respectively. Nonalcoholic steatohepatitis (NASH) with liver fibrosis was defined as Fibroscan-aspartate aminotransferase (AST) score (FAST) >0.35. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator proposed by the American Heart Association and computed from age, sex, race, lipid pattern, blood pressure, diabetes treatment and smoking. Based on the American Heart Association guidelines, the 10-year cardiovascular risk by ASCVD was categorized as low if <5%, borderline if 5%–7.4%, intermediate if 7.5%–19.9% and high if ≥20% or if previous cardiovascular event.Predictors of intermediate-high cardiovascular risk were investigated by multivariable logistic regression analysis. Result(s) We included 405 patients with IBD (54% female; mean age 45+15 years; mean BMI 26+5 Kg/m; 31% with ulcerative colitis; 7% with diabetes; 14% with hypertension). Overall, 278 (68%), 23 (6%), 47 (12%) and 57 (14%) were categorized as at low, borderline, intermediate and high ASCVD risk, respectively. NAFLD and significant liver fibrosis were found in 129 (32%) and 35 (9%) patients, respectively. NASH with fibrosis was found in 11 (3%) patients. Patients with NAFLD and with significant liver fibrosis diagnosed by TE with CAP had higher proportion of intermediate-high ASCVD risk category (see Figure). These findings were confirmed also in young IBD patients <55 years old with NAFLD. No difference in ASCVD risk was detected for FAST score. After adjusting for IBD disease activity, significant liver fibrosis and BMI, predictors of intermediate-high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.97, 95% confidence interval [CI] 1.56–5.68), IBD duration (aOR 1.55 per 10 years, 95% CI 1.22–1.97), and ulcerative colitis (aOR 2.32, 95% CI 1.35–3.98). Only 30% of IBD patients classified as intermediate-high ASCVD risk were on statin treatment, with no difference between patients with and without NAFLD. Image Conclusion(s) NAFLD increases cardiovascular risk, independently of age, IBD-related factors and BMI. A potential implication of our finding is the targeted cardiovascular assessment in IBD patients with NAFLD and appropriate initiation of statin, particularly if they have longer IBD duration and ulcerative colitis. Please acknowledge all funding agencies by checking the applicable boxes below CAG Disclosure of Interest None Declared

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. Both NAFLD and cardiovascular diseases seem more frequent in patients with inflammatory bowel disease (IBD). Purpose We aimed to assess the effect of NAFLD and associated liver fibrosis on the cardiovascular risk in people with IBD. Method We prospectively included IBD patients undergoing a routine screening program for NAFLD by transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD and significant liver fibrosis were defined as CAP >275 dB/m and liver stiffness measurement (LSM) by TE ≥8 kPa, respectively. Nonalcoholic steatohepatitis (NASH) with liver fibrosis was defined as Fibroscan-aspartate aminotransferase (AST) score (FAST) >0.35. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator proposed by the American Heart Association and computed from age, sex, race, lipid pattern, blood pressure, diabetes treatment and smoking. Based on the American Heart Association guidelines, the 10-year cardiovascular risk by ASCVD was categorized as low if <5%, borderline if 5%–7.4%, intermediate if 7.5%–19.9% and high if ≥20% or if previous cardiovascular event.Predictors of intermediate-high cardiovascular risk were investigated by multivariable logistic regression analysis. Result(s) We included 405 patients with IBD (54% female; mean age 45+15 years; mean BMI 26+5 Kg/m2; 31% with ulcerative colitis; 7% with diabetes; 14% with hypertension). Overall, 278 (68%), 23 (6%), 47 (12%) and 57 (14%) were categorized as at low, borderline, intermediate and high ASCVD risk, respectively. NAFLD and significant liver fibrosis were found in 129 (32%) and 35 (9%) patients, respectively. NASH with fibrosis was found in 11 (3%) patients. Patients with NAFLD and with significant liver fibrosis diagnosed by TE with CAP had higher proportion of intermediate-high ASCVD risk category (see Figure). These findings were confirmed also in young IBD patients <55 years old with NAFLD. No difference in ASCVD risk was detected for FAST score. After adjusting for IBD disease activity, significant liver fibrosis and BMI, predictors of intermediate-high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.97, 95% confidence interval [CI] 1.56–5.68), IBD duration (aOR 1.55 per 10 years, 95% CI 1.22–1.97), and ulcerative colitis (aOR 2.32, 95% CI 1.35–3.98). Only 30% of IBD patients classified as intermediate-high ASCVD risk were on statin treatment, with no difference between patients with and without NAFLD. Image Conclusion(s) NAFLD increases cardiovascular risk, independently of age, IBD-related factors and BMI. A potential deliverable of our finding is the targeted cardiovascular assessment in IBD patients with NAFLD and appropriate initiation of statin, particularly if they have longer IBD duration and ulcerative colitis. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Abstract Background Therapeutic drug monitoring, the measurement of serum biologic concentrations and immunogenicity, has become an important method in guiding the management of biologic therapy in patients with Crohn’s disease (CD). Ustekinumab, an inhibitor of the p40 subunit of interleukins 12 and 23, is an approved therapy for patients with CD. However, few studies have explored the relationship between serum ustekinumab drug levels and outcomes in CD. Thus, the utility of serum ustekinumab drug levels in the management of CD remains unknown. Aims The primary objective of the study was to evaluate the association between serum ustekinumab drug levels and endoscopic remission (ER) in CD. Secondary outcomes included evaluating the association between serum ustekinumab drug levels and clinical (CR), biochemical, and histological remission (HR). Methods Adult patients with CD maintained on ustekinumab were prospectively recruited at the time of routine colonoscopy from 2018 to 2021 at the Montreal University Health Centre, Montreal, Quebec. Clinical and demographic information was obtained from chart and patient review. CD symptom severity was assessed by the Harvey-Bradshaw Index (HBI), with clinical remission defined as an HBI score less than 5. Blood samples were drawn for measurement of serum ustekinumab drug level and C-reactive protein. Stool samples for fecal calprotectin were also collected. Elevated C-reactive protein and fecal calprotectin were defined as a value greater than 5 mg/L and 200 ug/g, respectively. Endoscopic remission was evaluated by the Simplified Endoscopic Score for Crohn’s Disease (SES-CD), with ER defined by an SES-CD score less than 3. If biopsies were taken, histological outcomes were recorded. HR was defined as inactive colitis. Results 53 patients were included in the study, of which 22 (41.5%) were in ER. Median [interquartile range] ustekinumab drug levels were not associated with ER (ER = 5.4 mg/L [2.6–9.4 mg/L], no ER = 4.3 mg/L [2.3–9.4 mg/L]; P=0.843). There was also no association between quartiles of ustekinumab drug levels and ER (P=0.772). In addition, there was no association observed between median ustekinumab drug level and CR (CR = 4.7 mg/L [2.7–8.3 mg/L], no CR = 3.8 mg/L [2.1–9.6 mg/L]; P=0.993) or HR (HR = 6.4 mg/L [3.5–9.5 mg/L], no HR = 3.7 mg/L [2.2–8.0 mg/L]); P=0.168). There was no association observed between median ustekinumab drug level and C-reactive protein or fecal calprotectin as well (P=0.158 and 0.923, respectively). Conclusions There was no association observed between serum ustekinumab drug levels and endoscopic remission. Further studies are required to validate our findings. Funding Agencies None

Abstract Background There was a significant progress in the medical therapy of inflammatory bowel disease(IBD) with the advent of biological compounds, yet patients may experience adverse events(AE): infusion reactions, serious infections and malignancies, understudied in vulnerable patient populations (e.g. elderly). Aims Our aim was to perform a systematic review to assess the safety of the biologic therapies in the elderly IBD population. Methods Medline databases and conferences proceedings were searched between January 1, 2010, and June 1, 2021. Two reviewers independently evaluated the collected studies based on inclusion and exclusion criteria. Search was focused on IBD/CD/UC, any biological therapy, and adverse events in the elderly. The methodological quality of the included studies was assessed using the Newcastle– Ottawa Scale (NOS). This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). 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. The majority of the studies were retrospective, merging IBD patients, with an age limit of 60 or 65 years for elderly, from Europe or North America. The gender ratio was equal except in the USA veteran database. The identified studies collected safety data on anti-TNF therapy, vedolizumab and ustekinumab. We selected studies with at least 1 year follow-up period. Ranges of AE rates(infliximab/adalimumab 6–39/100patient-years (PY), vedolizumab 6–26/100 PY and ustekinumab 6–18.2/100 PY), infection rates (anti TNF 2.5–31/100PY, vedolizumab 2.6–77/100 PY and ustekinumab 5.2–35.7/100 PY) or infusion/injection reactions (anti TNF 0–14/100PY, vedolizumab 0.9–5/100 PY and ustekinumab 0–2.6/100 PY), were not different among the biological medication. Conclusions We report for the first time the comparative safety of biological therapies in elderly IBD patients. Ranges of adverse events or infections were wide but not different among the medications. Current data are insufficient to suggest prioritizing among biologicals in the elderly based on the safety, larger studies in elderly IBD patients are warranted. Funding Agencies None

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.

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.

Abstract Background Data suggests that tight objective monitoring of inflammatory bowel diseases (IBD) may improve one-year clinical outcomes. Aims The goal of this study is to assess the adherence to serial tight objective monitoring, via clinical symptoms and biomarkers, and the effect of such tight monitoring on one year outcome in IBD patients at an academic and an university-affiliated center. Methods We retrospectively reviewed the chart of 428 consecutive IBD patients who started adalimumaby at the McGill University Health Center and Jewish General Hospital (Montreal, Canada) between January 1, 2015 and January 1, 2019 [338 Crohn’s disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms (assessed by Harvey-Bradshaw-Index and partial Mayo), C-Reactive Protein(CRP), and fecal calprotectin(FCAL) were captured at treatment initiation and at 3, 6, 9, and 12 months. Combined adherence was defined as the evaluation of ≥2 of 3 parameters(clinical, CRP, FCAL). Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method. Results Clinical symptoms were assessed in nearly all patients at 3 (CD-UC:95-94%), 6 (90-83%), 9 (86-85%) and 12 (96-89%) months. CRP was also available for most patients but the frequency of assessment decreased in CD patients over the study period. In comparison, compliance to serial FCAL testing was low throughout the follow-up period. Clinical remission at one-year was significantly higher in patients who were adherent to early assessment visit at 3 months (p=0.001 both for CD and UC). Adherence to early follow-up also resulted in earlier dose optimisation in both CD and UC patients(pLogrank=0.026 for UC and p=0.09 for CD). However, the overall drug sustainability did not differ. Conclusions Clinical assessment and CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization and improved one-year clinical outcomes but did not change drug sustainability rates. Funding Agencies None

Background and Aims. The impact of COVID-19 has been of great concern in patients with inflammatory bowel disease (IBD) worldwide, including an increased risk of severe outcomes and/or possible flare of IBD. This study aims to evaluate prevalence, outcomes, the impact of COVID-19 in patients with IBD, and risk factors associated with severe COVID-19 or flare of IBD activity. Methods. A consecutive cohort of IBD patients who were diagnosed with COVID-19 infection and followed up at the McGill University Health Care Centre was obtained between March 1, 2020, and April 30, 2021. Demographics, comorbidities, IBD (type, treatments, pre- and post-COVID-19 clinical activity, biomarkers, and endoscopic activity), and COVID-19-related outcomes (pneumonia, hospitalization, death, and flare of IBD disease) were analyzed. Results. A cohort of 3,516 IBD patients was included. 82 patients (2.3%) were diagnosed with COVID-19 infection (median age: 39.0 (IQR 27.8–48.0), 77% with Crohn’s disease, 50% were female). The prevalence of COVID-19 infection in IBD patients was significantly lower compared to the general population in Canada and Quebec (3.5% versus 4.3%, p < 0.001 ). Severe COVID-19 occurred in 6 patients (7.3%); 2 patients (2.4%) died. A flare of IBD post-COVID-19 infection was reported in 8 patients (9.8%) within 3 months. Biologic therapy was held during active COVID-19 infection in 37% of patients. Age ≥55 years (odds ratio (OR): 11.1, 95% CI: 1.8–68.0), systemic corticosteroid use (OR: 4.6, 95% CI: 0.7–30.1), active IBD (OR: 3.8, 95% CI: 0.7–20.8), and comorbidity (OR: 4.9, 95% CI: 0.8–28.6) were factors associated with severe COVID-19. After initial infection, 61% of IBD patients received COVID-19 vaccinations. Conclusion. The prevalence of COVID-19 infection among patients with IBD was lower than that in the general population in Canada. Severe COVID-19, mortality, and flare of IBD were relatively rare, while a large proportion of patients received COVID-19 vaccination. Older age, comorbidities, active IBD disease, and systemic corticosteroid, but not immunosuppressive or biological therapy, were associated with severe COVID-19 infection.

Abstract Background Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine how strong patient reported outcomes, clinical scores and symptoms correlate with endoscopy for assessment of disease activity in UC patients. Methods 171 patients were included prospectively and consecutively (age: 49 (IQR: 38-61) years, duration 12 (4-19)years, 79 females (46.2%), 57.3% extensive disease, 42.7% on biologicals) at the time of the colonoscopy. The 2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES), Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C reactive Protein (CRP) and fecal calprotectin (FCAL) was available in 83 and 45.6% of patients. 17.0% had clinical flare, treatment was escalated in 14.6% of patients. Sensitivity, specificity, PPV and NPV values were calculated, ROC analysis and K-statistics were performed. Results Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission were similarly associated to mucosal healing defined by MES (0 or ≤1) or Baron (0 or ≤1) scores (Table 1). PRO2 (AUCMES0/Baron0: 0.770/0.740, AUCMES0-1/Baron0-1: 0.868/0.858), SF (AUCMES0/Baron0:0.751/0.724, AUCMES0-1/Baron0-1:0842/0.820), RBS (AUCMES0/Baron0: 0.718/0.698, AUCMES0-1/Baron0-1: 0.814/0.845) partial Mayo (AUCMES0/Baron0: 0.823/0.788, AUCMES0-1/Baron0-1: 0.927/0.902) and SCCAI (AUCMES0/Baron0: 0.767/0.752, AUCMES0-1/Baron0-1:0.888/0.867) were similarly associated with mucosal healing in a ROC analysis. There was a strict association between MES 0 and Baron 0 (k=0.917) and UCEIS <4 and MES 0-1 (k=0.813), while moderate to fair agreement between UCEIS <4 and MES 0 (K=0.471) or Baron 0 (K=0.414)/Baron 0-1 (K=0.353), and between MES 0-1 and Baron 0-1 (K= 0.350) scores. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K~0.2), while agreement between FCAL (>100 or >250) and RBS-PRO2 remission (K>100 or >250: 0.44-0.60) or pMAYO (K>100 or >250: 0.41-0.59) or MES/Baron 0 was moderate to good (K>100:0.53-0.52 and K>250:0.57-0.53). Conclusion We found no difference across accuracy of RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing. A strong association was found with high PPV for MES/Baron ≤1 and high NPV for MES/Baron 0. FCAL, but not CRP was associated to clinical and endoscopic remission.

Background: Data suggests that tight objective monitoring may improve clinical outcomes in IBD. Aim: To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. Methods: We retrospectively reviewed the chart of 428 consecutive IBD patients started on adali-mumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clin-ical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal cal-protectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose op-timization and drug sustainability curves were plotted by Kaplan-Meier method. Results: Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose opti-mization in CD and UC patients(pLogrank = 0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ. Conclusion: Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Ad-herence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Abstract Background Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine the operating characteristics of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), to quantify the cut off most closely correlated with clinical remission or activity and determine agreement with the Mayo endoscopic subscore (MES), Baron score, clinical scores and biomarkers. Methods 171 patients were included prospectively and consecutively (age: 49 (IQR: 38–61) years, duration 12 (4–19)years, 79 females (46.2%), 57.3% extensive disease, 42.7% on biologicals) at the time of the colonoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Mayo endoscopic subscore (MES), Baron scores were calculated, as well as the 2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI). C reactive Protein (CRP) and fecal calprotectin (FCAL) was available in 83 and 45.6% of patients. 17.0% had clinical flare, treatment was escalated in 14.6% of patients. Sensitivity, specificity, PPV and NPV values were calculated, ROC analysis and K-statistics were performed. Results UCEIS was strongly associated to PRO2 SF (AUC:0.863), RBS (AUC:0.924), PRO2 combined (AUC:0.898), partial MAYO (AUC:0.945) and SCCAI (AUC:0.901) remission in a ROC analysis. A UCEIS of ≤3 was identified as the best cut-off to identify RBS subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission, while a UCEIS≥4 identified active disease frequently needing change in medical therapy. A moderate agreement was found between UCEIS <4 and MES 0 (K=0.471) or Baron 0 (K=0.414)/Baron 0–1 (K=0.353). Correlation between FCAL and UCEIS (coeff:0.701, p<0.0001) was strong, while modest only with CRP (coeff:0.248, p=0.01). Conclusion UCEIS was strongly associated with clinical remission defined as PRO2, SF, RBS, partial Mayo or SCCAI with best agreement with RBS and partial Mayo remission. A UCEIS of ≤3 was identified as a cut-off for quiescent disease, while a UCEIS≥4 identified active disease, which can support clinical decision-making based on endoscopic findings. Agreement between UCEIS and FCAL was strong, while agreement with UCEIS and MES/Baron scores was moderate.