Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis.

INTRODUCTION: Endoscopic healing is currently considered the main target in the management of ulcerative colitis (UC). There are conflicting data about the role of histology as a stricter treatment objective. We aim at evaluating the additional benefit of histologic remission over endoscopic remission. METHODS: We performed a prospective observational study at the McGill University Health Center. We enrolled adult patients with UC in clinical remission for at least 3 months undergoing a colonoscopy. Endoscopic disease activity was based on the Mayo endoscopic score. Rectal biopsies were obtained, and the histologic activity was evaluated using the Geboes score (active disease defined as Geboes score ≥ 3.1) with the addition of assessing the presence of basal plasmacytosis. Patients were followed up for 12 months for disease relapse defined as a partial Mayo score of > 2. At the time of relapse or end of follow-up, all patients underwent repeat endoscopic evaluation. The primary end point was clinical relapse. RESULTS: Two hundred fifty-three patients were included. The presence of basal plasmacytosis was associated with relapse (adjusted odd ratio = 2.07, 95% confidence interval [CI] 1.06-4.18, P = 0.042). Time to clinical relapse was significantly higher for patients with Mayo endoscopic score > 0 with adjusted hazard ratio = 2.65, 95% CI 1.31-5.39, and P = 0.007. Time to clinical relapse was not significantly higher for Geboes score ≥ 3.1 with adjusted hazard ratio = 1.29, 95% CI 0.67-2.49, and P = 0.45. DISCUSSION: Active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis is associated with relapse.

Patient-Reported Outcome and Clinical Scores Are Equally Accurate in Predicting Mucosal Healing in Ulcerative Colitis: A Prospective Study.

BACKGROUND: Optimal management of patients with ulcerative colitis (UC) requires the accurate, objective assessment of disease activity. AIMS: We aimed to determine how strong patient-reported outcomes, clinical scores and symptoms correlate with endoscopy and biomarkers for assessment of disease activity in patients with UC. METHODS: Consecutive patients with UC followed at the McGill University IBD Center and referred for endoscopy (surveillance or flare) were included prospectively between September 2018 and August 2020. Patient-reported outcome (PRO2), partial Mayo, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES) and Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C-reactive protein (CRP) and fecal calprotectin (FCAL) were collected. RESULTS: A total of 171 patients with UC [age: 49(IQR:38-61) years, female: 46.2%, 57.3% extensive disease, 42.7% on biologicals] were included prospectively. Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS0 and SF ≤ 1), partial Mayo (≤ 2) and SCCAI (≤ 2.5) remission were similarly associated with mucosal healing defined by MES (0 or ≤ 1), Baron (0 or ≤ 1) or UCEIS (≤ 3) scores in ROC analysis (AUC:0.93-0.72). There was a moderate-to-strong agreement between MES Baron and UCEIS (K = 0.91-0.41). A UCEIS of ≤ 3 was identified as the best cutoff to clinical or endoscopic remission. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K ~ 0.2), while agreement between FCAL and RBS-PRO2 or MES/Baron/UCEIS was moderate to strong (K = 0.44-0.70). CONCLUSIONS: Agreement between RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing was moderate to strong, while no clinically meaningful difference was found in accuracy across the scores and definitions. FCAL, but not CRP, was associated to clinical and endoscopic remission.

Poor Drug Sustainability in Inflammatory Bowel Disease Patients in Clinical Remission on Thiopurine Monotherapy.

BACKGROUND: Immunomodulator monotherapy is an important component in the treatment of inflammatory bowel disease (IBD). However, there is conflicting literature about thiopurines maintaining long-term remission in patients with active IBD. AIM: To determine the durable clinical remission rate in adults with Crohn's disease (CD) or ulcerative colitis (UC) on thiopurine monotherapy over 5 years. METHODS: We performed a retrospective analysis of adult patients identified at McGill University Health Centre from 2009 to 2012. We included IBD patients who initiated thiopurine monotherapy and were in remission for at least 3 months (Harvey-Bradshaw Index (HBI) < 5 points for CD and partial Mayo Score (pMS) < 2 points in UC). The primary endpoint was sustained clinical remission on thiopurines during a 5-year follow-up. This included patients who had not relapsed or discontinued the drug due to side effects. The secondary endpoint was clinical relapse over the follow-up period, which was defined as HBI > 5 in CD and pMS > 2 in UC. RESULTS: There were 148 patients included in the study (100 CD; 48 UC). At 5 years, 23% (34/148) patients remained in clinical remission on thiopurine monotherapy (25 CD and 9 UC patients). Thirty-three percent (33/100) of CD and 46% (22/48) of UC patients relapsed while on thiopurines. There was no difference in relapse rates between CD and UC patients. Eighty-four percent (42/50) of patients with CD with side effects and all UC (17/17) patients who experienced side effects discontinued the drug. CONCLUSION: This analysis demonstrates that there is poor sustainability of clinical remission in IBD patients on thiopurine monotherapy given that a high proportion of patients discontinue thiopurines due to either relapse or side effects.

Low Rate of Drug Discontinuation, Frequent Need for Dose Adjustment, and No Association with Development of New Arthralgia in Patients Treated with Vedolizumab: Results from a Tertiary Referral IBD Center.

BACKGROUND: Evaluating clinical data on the safety and efficacy of vedolizumab (VDZ) in 'real-world' setting is still desirable. Recent reports have raised concerns that arthralgia may be associated with VDZ. AIMS: The aim of this study is to present clinical experience with VDZ from a tertiary IBD center. METHODS: Retrospective chart reviews were performed of consecutive patients exposed to VDZ between 2015 and 2018. Clinical, biomarker, and endoscopic efficacy and safety data were evaluated. RESULTS: A total of 130 IBD (75CD, 55UC) patients were included. Median duration of VDZ therapy was 65 weeks. Probability of drug discontinuation was 4.9% and 9.4% at 1 and 2 years. Dose intensification was more frequent in CD compared to UC (at 1 and 2 years: 64.8/87.9% vs. 26.5/35.7%, p < 0.001). Clinical remission rates at 3-, 6- and 12 months were 44.4%, 71.4% and 77.1% in UC, and 9.1%, 26.7% and 29.2% in CD patients, respectively. Prior use of multiple biologic agents was associated with diminished efficacy of VDZ in CD. Three new cases of arthralgia were encountered during follow-up. CONCLUSION: Vedolizumab (VDZ) therapy displayed good drug sustainability and clinical efficacy in a population with severe disease phenotype and high rates of previous anti-TNF failure. Frequent dose intensification was required. The safety profile was good, and no association between newly onset arthralgia and VDZ therapy was observed.

Clinical Parameters Correlate With Endoscopic Activity of Ulcerative Colitis: A Systematic Review.

BACKGROUND & AIMS: Optimal management of patients with ulcerative colitis (UC) requires assessment of disease activity-usually by endoscopy, which is invasive, costly, and not risk free. We performed a systematic review to determine whether clinical symptoms correlate with findings from endoscopy assessments of patients with UC. METHODS: We performed a systematic review of publication databases from January 1980 through July 2018 to identify clinical trials and observational studies reporting correlations among symptoms, disease activity index scores and/or patient reported outcomes (rectal bleeding and/or stool frequency), and endoscopic disease activity. Correlations were ascertained in patients with active vs inactive disease and by disease extent and treatment type. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Because of significant heterogeneity, meta-analysis was not possible. Results were synthesized qualitatively and systematically. RESULTS: Our final analysis included 23 studies (1 randomized trial, 22 observational studies) comprising 3320 patients with UC. The studies used a variety of measures to assess clinical activity, endoscopic activity, and measures of correlation (sensitivity, specificity, correlation coefficients, area under the receiver operator curve). Overall, studies were at moderate-high risk of bias. Composite clinical measures, including rectal bleeding and stool frequency, had moderate to strong correlations with endoscopic disease activity; the absence of rectal bleeding identified patients with inactive disease with higher levels of sensitivity than normalization of stool frequency. In general, symptoms correlated more strongly with endoscopic activity in patients with left-sided colitis than extensive colitis. The effect of different medications on the correlation between clinical and endoscopic activity has not been well studied. CONCLUSIONS: In a systematic review, we found a moderate to strong correlation between clinical activity, particularly the combination of rectal bleeding and stool frequency, and endoscopic activity in patients with UC. Although these clinical assessments could help prioritize patients for endoscopic evaluation in resource-limited settings, challenges associated with treating patients based on symptoms alone preclude adaptation of current management algorithms.

Clinical efficacy and nocebo effect following non-medical biosimilar switch in patients with inflammatory bowel disease: A prospective observational study.

BACKGROUND: We aimed to evaluate clinical efficacy, biomarker activity, therapeutic drug monitoring (TDM), adverse events (AEs), and nocebo effect in inflammatory bowel disease (IBD) patients who underwent non-medical biosimilar switching. METHODS: A prospective observational study of consecutive IBD patients who underwent biosimilar switch. Disease activity, biomarkers, TDM, and AEs, including the nocebo effect were captured 8 weeks before switch, at the time of switch (baseline),12 and 24 weeks after the switch. RESULTS: 210 patients were included [81.4% had Crohn's disease (CD), the median age at inclusion: 42 years (IQR 29-61)]. There was no significant difference in the rates of clinical remission at week 8 before switch, baseline, week12, and 24 after switch: 89.0%,93.4%,86.3%,and 90.8%,p = 0.129. The biomarker remission rates were not significantly different; CRP:81.3%,74.7%,81.2%,73.0%,p = 0.343; fecal calprotectin: 78.3%,74.5%,71.7%,76.3%,p = 0.829. The rates of maintaining therapeutic levels (84.7%,83.9%,83.0%,85.3%,p = 0.597) and prevalence of positive anti-drug antibodies remained unchanged. Drug persistence at 12 week of switch was 97.1%, regardless of disease phenotype and originator. The nocebo effect was observed in 13.3%. The discontinuation rate was 4.8%. CONCLUSION: Despite a significant number of early nocebo complaints within the first 6 months after the biosimilar switch, no significant changes were found in clinical efficacy, biomarkers, therapeutic drug level, or anti-drug antibodies.

Nonalcoholic Fatty Liver Disease Increases Cardiovascular Risk in Inflammatory Bowel Diseases.

Background: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. Both conditions seem more frequent in patients with inflammatory bowel disease (IBD). We aimed to assess the effect of NAFLD and liver fibrosis on intermediate-high cardiovascular risk in IBD. Methods: 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-1 and liver stiffness measurement by TE ≥8 kPa, respectively. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator and 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. Results: Of 405 patients with IBD included, 278 (68.6%), 23 (5.7%), 47 (11.6%), and 57 (14.1%) were categorized as at low, borderline, intermediate, and high ASCVD risk, respectively. NAFLD and significant liver fibrosis were found in 129 (31.9%) and 35 (8.6%) patients, respectively. After adjusting for disease activity, significant liver fibrosis and body mass index, predictors of intermediate-high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.97, 95% 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). Conclusions: Assessment of cardiovascular risk should be targeted in IBD patients with NAFLD, particularly if they have longer IBD duration and ulcerative colitis.

Mucosal Healing and Clinical Efficacy of Adalimumab in Small Intestinal Crohn's Disease (SIMCHA Study): Final Results From a Prospective, Open-Label, Single-Arm Study.

BACKGROUND: Endoscopic healing is a key treatment target in inflammatory bowel disease; few data are available on the clinical and endoscopic efficacy of biological therapy in upper gastrointestinal Crohn's disease. This study aimed to investigate small bowel mucosal healing and clinical efficacy of adalimumab therapy by video capsule endoscopy in patients with endoscopically active upper gastrointestinal Crohn's disease. METHODS: This prospective, open-label, single-arm study included Crohn's disease patients with moderate-severe endoscopic proximal small bowel involvement, defined by a Lewis score >790. Patients were treated with adalimumab monotherapy for 24 weeks. Co-primary outcomes were endoscopic healing, defined as Lewis score <350, and endoscopic response, defined as >50% decrease in Lewis score. Secondary outcomes included clinical (Harvey-Bradshaw index <4) and biomarker remission (fecal calprotectin <250 µg/g, and C-reactive protein <5 mg/L). RESULTS: A total of 59 Crohn's disease patients were screened; 17 patients have met eligibility criteria and were enrolled. Endoscopic healing was observed in 8 patients (47.1%) and endoscopic response in additional 5 patients (29.4%) at 24 weeks. Median Lewis score was significantly decreased compared to baseline (1912 vs. 337, P = .0005). Eleven of 13 patients (84.6%) with clinical activity achieved clinical remission (baseline: 13/17 vs. week 24: 2/17, P < .0001). Nine of 10 patients with elevated C-reactive protein achieved normal C-reactive protein after treatment and the median C-reactive protein significantly decreased from 7.4 to 1.6 mg/L, P = .032. In contrast, no change was observed in fecal calprotectin pre- and posttreatment. CONCLUSIONS: Adalimumab induced endoscopic healing and clinical remission in patients with active small bowel Crohn's disease, with approximately half of the patients achieving endoscopic healing.

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.

Safety of Biological Therapies in Elderly Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

Background and Aim: Newer biologics appeared safer in landmark clinical trials, but their safety is understudied in vulnerable populations. The aim of the present study was to perform a systematic review and meta-analysis to assess the safety of available biologicals in the elderly IBD population. Methods: We systematically searched PubMed/Medline and conference proceedings between 1 April 1969 and 1 June 2021 to identify eligible studies that examined the safety of biologics in elderly patients with IBD. Of the 2885 articles and 12 congress abstracts identified, 12 peer reviewed papers and 3 abstracts were included after independent evaluation by two reviewers. The identified studies collected safety data on anti-TNF, vedolizumab (VDZ) and ustekinumab (UST). Results: Rates of AE and infections were not different among the biologics (AE mean rate: 11.3 (CI 95% 9.9-12.7)/100 pts-years; p = 0.11, infection mean rate: 9.5 (CI 95% 8.4-10.6)/100 pts-years; p = 0.56) in elderly IBD patients on anti-TNF, VDZ or UST. Infusion/injection reaction rates were more common on anti-TNFs (mean rate: 2.51 (CI 95% 1.7-3.4/100 pts-years; p = 0.02). and malignancy rates were higher on VDZ/UST (mean rate: 2.14 (CI 95% 1.6-2.8)/100 pts-years; p = 0.01). Conclusions: Rates of AEs and infections were not different among biologicals. Infusion/injection reactions were more common on anti-TNFs. Current data are insufficient to suggest the sequencing of biologicals in elderly patients based on safety.

Effectiveness, safety, and drug sustainability of biologics in elderly patients with inflammatory bowel disease: A retrospective study.

BACKGROUND: Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease (IBD) however data on the efficacy and side effects of these therapies in the elderly is scant. AIM: To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population. METHODS: Consecutive elderly (≥ 60 years old) IBD patients, treated with biologics [infliximab (IFX), adalimumab (ADAL), vedolizumab (VDZ), ustekinumab (UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020. Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events (AEs) or serious AE were collected during and within three months of stopping of the biologic therapy. RESULTS: We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn's disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX (28.5%), ADAL (38.7%), VDZ (15.6%), UST (17%). The mean duration of biologic treatment was 157.5 (SD = 148) wk. Parallel steroid therapy was given in 34% at baseline, 19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability (P = 0.195), time to adverse event (P = 0.158) or infection rates (P = 0.973) between the four biologics studied. The most common AEs that led to drug discontinuation were loss of response, infusion/injection reaction and infection. CONCLUSION: Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals.

Adherence to Objective Therapeutic Monitoring and Outcomes in Patients with Inflammatory Bowel Disease with Adalimumab Treatment. A Real-world Prospective Study.

BACKGROUND AND AIMS: Objective monitoring and effective early treatment using a treat-to-target approach are key to improving therapeutic outcomes in IBD patients. This study aimed to assess adherence to objective monitoring (clinical, biomarkers, and endoscopy) and its impact on clinical outcomes. METHODS: A prospective, multicenter study included consecutive IBD patients starting on adalimumab therapy between January 2019 and December 2020. Disease activity, assessed by the Harvey-Bradshaw index (HBI), partial Mayo, C-reactive protein (CRP), fecal calprotectin (FCAL), and endoscopy were evaluated at adalimumab initiation and 3, 6, 9 and 12 months. Therapeutic drug monitoring, changes in treatment, drug sustainability, and clinical outcomes were assessed. RESULTS: 104 IBD patients were enrolled (78.8% CD, median age 34.3 years, disease duration 9 years). During the 12 months follow-up, high adherence to clinical activity assessment was observed in both CD (81.3%- 87.7%) and UC patients (76.5-90.9%). CRP measurement decreased over time in both CD (37.3%-54.9%) and UC (29.4%-50.0%). The adherence to serial FCAL monitoring was low in CD (22.7-31.3%) and UC patients (17.6-56.0%). UC patients had higher adherence to early endoscopic assessment (<6 months) compared to CD patients (40.9% vs. 21.5%). Adherence to early combined clinical and biomarkers resulted in earlier dose optimization in CD and UC (log-rank<0.001), but drug sustainability was not different. The patients with early combined adherence had a significantly higher clinical remission rate at 1 year compared to non-adherence (70.2% vs. 29.8%, p=0.007) but no significant difference in UC patients. CONCLUSIONS: The adherence to early objective monitoring with combined clinical and biomarkers assessment in IBD patients starting adalimumab therapy led to dose optimization and improved 1-year clinical remission in CD but did not change drug sustainability and clinical remission in UC.

Clinical Outcomes of COVID-19 and Impact on Disease Course in Patients with Inflammatory Bowel Disease.

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.

No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015.

BACKGROUND: Crohn disease (CD) and ulcerative colitis (UC) have high health care expenditures because of medications, hospitalizations, and surgeries. We evaluated disease outcomes and treatment algorithms of patients with inflammatory bowel disease (IBD) in Québec, comparing periods before and after 2010. METHODS: The province of Québec's public health administrative database was used to identify newly diagnosed patients with IBD between 1996 and 2015. The primary and secondary outcomes included time to and probability of first and second IBD-related hospitalizations, first and second major surgery, and medication exposures. Medication prescriptions were collected from the public prescription database. RESULTS: We identified 34,644 newly diagnosed patients with IBD (CD = 59.5%). The probability of the first major surgery increased after 2010 in patients with CD (5 years postdiagnosis before and after 2010: 8% [SD = 0.2%] vs 15% [SD = 0.6%]; P < 0.0001) and patients with UC (6% [SD = 0.2%] vs 10% [SD = 0.6%] ;P < 0.0001). The probability of the second major surgery was unchanged in patients with CD. Hospitalization rates remained unchanged. Patients on anti-tumor necrosis factor (anti-TNF) medications had the lowest probability of hospitalizations (overall 5-year probability in patients with IBD stratified by maximal therapeutic step: 5-aminosalicylic acids 37% [SD = 0.6%]; anti-TNFs 31% [SD = 1.8%]; P < 0.0001). Anti-TNFs were more commonly prescribed for patients with CD after 2010 (4% [SD = 0.2%] vs 16% [SD = 0.6%]; P < 0.0001) in the public health insurance plan, especially younger patients. Corticosteroid exposure was unchanged before and after 2010. Immunosuppressant use was low but increased after 2010. The use of 5-ASAs was stable in patients with UC but decreased in patients with CD. CONCLUSIONS: The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs.

The Burden of Anemia Remains Significant over Time in Patients with Inflammatory Bowel Diseases at a Tertiary Referral Center.

BACKGROUND AND AIMS: Anemia is a common complication of inflammatory bowel diseases (IBD), as well as a predictor of poor outcomes. The aim of this study was to determine the prevalence of anemia over time and the management of moderate to severe anemia at a tertiary referral IBD center. METHODS: We retrospectively reviewed the occurrence of anemia at the time of referral or diagnosis and during follow-up at the McGill University Health Centre IBD center. Consecutive patients presenting with an outpatient visit between July and December 2016 and between December 2018 and March 2019 were included. Disease characteristics, biochemistry and medical management, including the need for intravenous iron therapy were recorded. RESULTS: 1,356 Crohn's disease (CD) and 1,293 ulcerative colitis (UC) patients [disease duration: 12 (IQR: 6-22) and 10 (IQR: 5-19) years respectively] were included. The prevalence of moderate to severe anemia at referral/diagnosis (15.4% and 8.5%) and during follow-up (11.1% and 8.1%) were higher in CD than in UC patients. In CD, previous resective surgery, perianal disease and elevated C-reactive protein (CRP) at assessment, while in UC steroid therapy, an elevated CRP and fecal calprotectin at assessment were associated with anemia in a multivariate analysis. Anemia improved by >2g/dL in 56.5% after 4-6 weeks (intravenous iron dose >1000 mg in 87% of patients). CONCLUSION: Anemia occurred frequently in this IBD cohort, at referral to the center and during follow-up, and contributes to the burden of IBD in referral populations. Most patients were assessed for anemia regularly and with accurate anemia workup; however, the targeted management of moderate to severe anemia was suboptimal.

Benefits of implementing a rapid access clinic in a high-volume inflammatory bowel disease center: Access, resource utilization and outcomes.

BACKGROUND: Emergency situations in inflammatory bowel diseases (IBD) put significant burden on both the patient and the healthcare system. AIM: To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service (RAC) at a tertiary IBD center. METHODS: Patient access, resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational study. For comparing resource utilization and healthcare costs, emergency department (ED) visits of IBD patients with no access to RAC services were evaluated between January 2018 and January 2019. Time to appointment, diagnostic methods, change in medical therapy, unplanned ED visits, hospitalizations and surgical admissions were calculated and compared. RESULTS: 488 patients (Crohn's disease: 68.4%/ulcerative colitis: 31.6%) contacted the RAC with a valid medical reason. Median time to visit with an IBD specialist following the index contact was 2 d. Patients had objective clinical and laboratory assessment (C-reactive protein and fecal calprotectin in 91% and 73%). Fast-track colonoscopy/sigmoidoscopy was performed in 24.6% of the patients, while computed tomography/magnetic resonance imaging in only 8.1%. Medical therapy was changed in 54.4%. ED visits within 30 d following the RAC visit occurred in 8.8% (unplanned ED visit rate: 5.9%). Diagnostic procedures and resource utilization at the ED (n = 135 patients) were substantially different compared to RAC users: Abdominal computed tomography was more frequent (65.7%, P < 0.001), coupled with multiple specialist consults, more frequent hospital admission (P < 0.001), higher steroid initiation (P < 0.001). Average medical cost estimates of diagnostic procedures and services per patient was $403 CAD vs $1885 CAD comparing all RAC and ED visits. CONCLUSION: Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care, optimized resource utilization and helped avoiding ED visits and subsequent hospitalizations.

Phenotypic and genotypic characteristics of inflammatory bowel disease in French Canadians: comparison with a large North American repository.

OBJECTIVES: Phenotype characteristics of inflammatory bowel disease (IBD) may differ significantly among ethnic subpopulations. The aim of this study was to characterize the IBD phenotype in French Canadians, the most prominent founder population in North America. METHODS: Using well-characterized phenotype data in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-IBD Genetics Consortium repository on patients with IBD, we compared phenotypic characteristics of 202 French Canadians with those of 1,287 other Caucasian patients. These included diagnosis, anatomical location, disease behavior, extraintestinal manifestations, surgical history, and family history of IBD. RESULTS: French-Canadian patients with Crohn's disease (CD) were less likely to have stricturing disease (11 vs. 21%, P=0.005; odds ratio (OR): 0.45, 95% confidence interval (95% CI): 0.24-0.85). Using a stringent definition of ethnicity (three out of four grandparents being French Canadians, as opposed to self-report, n=148), French Canadians had a tendency toward developing fistulizing CD (37 vs. 28%, P=0.07), and there was an increased prevalence of sacroiliitis among those with IBD (4 vs. 2%, P=0.045). Among French Canadians, the numbers of current smokers in CD (40 vs. 25%, P=0.006) and former smokers in ulcerative colitis (UC) (35 vs. 20%, P=0.03) were significantly higher. The prevalence of one of the three main variants of nucleotide-binding oligomerization domain containing 2 (NOD2) single-nucleotide polymorphisms (SNPs) among French-Canadian CD patients was 43.2%. The 3020insC SNP correlated with small bowel disease in French Canadians (25 [corrected] vs. 0%, P=0.006). CONCLUSIONS: French Canadians show an IBD phenotype profile distinct from other Caucasian IBD populations, with an accentuated association between smoking status and IBD. This unique profile may have implications regarding the need for a different approach to the management of IBD in this population.

Dexamethasone and GLP-2 given to lactating rat dams influence glucose uptake in suckling and postweanling offspring.

BACKGROUND: Glucagon-like peptide-2 (GLP-2) enhances intestinal absorption in adult animals. Glucocorticosteroids accelerate the ontogeny of the intestine and increase sugar uptake in adult animals. Modifying the maternal diet during lactation alters nutrient uptake in the offspring. The authors hypothesized that GLP-2 and dexamethasone, when administrated to lactating rat dams, enhance sugar uptake in the suckling and postweanling offspring. METHODS: Rat dams were treated during lactation with GLP-2 (0.1 microg/g/day subcutaneously [SC], twice daily), dexamethasone (0.128 microg/g/day SC, once daily), GLP-2 + dexamethasone (same doses), or placebo. The suckling offspring were sacrificed at 19-21 days of age, and the postweanlings were sacrificed 4 weeks later. Intestinal glucose and fructose uptake was assessed using an in vitro ring technique. RESULTS: GLP-2 and dexamethasone resulted in lower body weights, and dexamethasone caused intestinal atrophy in sucklings. The jejunal atrophy in sucklings given dexamethasone was prevented by GLP-2 + dexamethasone. In sucklings, the maximal transport rate and the Michaelis affinity constant for ileal glucose uptake were both increased by GLP-2 and GLP-2 + dexamethasone. In contrast, in postweanlings, the maximal transport rate for jejunal glucose uptake was reduced by dexamethasone and GLP-2, as was ileal fructose uptake. CONCLUSIONS: Treating lactating rat dams with GLP-2 or dexamethasone enhances glucose uptake in sucklings, but the late effect is a reduction in glucose and fructose absorption in postweanlings. The nutritional significance of these findings remains to be established.

Maladaptive coping, low self-efficacy and disease activity are associated with poorer patient-reported outcomes in inflammatory bowel disease.

BACKGROUND/AIMS: Patient-reported outcomes (PRO) are key aspects in the management of inflammatory bowel disease (IBD). This study aims to evaluate factors associated with adverse PRO, including modifiable social constructs of maladaptive coping and self-efficacy as well as physician-patient concordance on PRO. PATIENTS AND METHODS: This cross-sectional study was performed in patients with Crohn's disease (CD) or ulcerative colitis (UC) from September 2015 to March 2016. Validated questionnaires were used to assess quality of life (Short IBD Questionnaire), disability (IBD disability index), productivity (work productivity and activity impairment questionnaire), anxiety/depression (Hospital Anxiety and Depression Scale), coping strategies [Brief Coping Operations Preference Enquiry (Brief COPE)], and self-efficacy (General Self-Efficacy Scale). Independent physician assessment was used to compare concordance with patients. RESULTS: In all, 207 (CD: 144 and UC: 63) patients, with median age of 39 years, were included, with 42.5% males. Significant proportion of patients reported moderate/severe impairment of disability (30.5%), quality of life (29.4%), productivity (52.4%), anxiety (32.9%) and depression (23.3%). Disease activity and maladaptive coping were independently associated with unfavourable PRO, whereas self-efficacy had a positive effect in multivariate analysis. Physicians could accurately identify the magnitude of PRO impairment in standard clinical settings (r = 0.59-0.65, P < 0.001). CONCLUSION: Disease activity and modifiable psychological constructs are associated with unfavorable PRO in patients with IBD. These factors could assist with identifying high-risk patients, many of whom may benefit from targeted interventions to improve health outcomes.

Screening for Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Diseases: A Cohort Study Using Transient Elastography.

Background: Inflammatory bowel disease (IBD) patients may be at risk for nonalcoholic fatty liver disease (NAFLD) due to chronic inflammation, hepatotoxic drugs, and alteration of the gut microbiota. Prospective data using accurate diagnostic methods are lacking. Methods: We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in IBD patients as part of a routine screening program. NAFLD was defined as CAP ≥248 dB/m. Significant liver fibrosis (stage 2 or higher out of 4) was defined as TE measurement ≥7.0 kPa. Predictors of NAFLD and significant liver fibrosis were determined by logistic regression analysis. Results: A total of 384 patients (mean age 42.4 years, 45.0% male, 64.6% with Crohn's disease) with no significant alcohol intake were included. Prevalence of NAFLD and significant liver fibrosis was 32.8% and 12.2%, respectively. Independent predictors of NAFLD were older age (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.15-1.82), higher body mass index (BMI; aOR, 1.31; 95% CI, 1.20-1.42) and higher triglycerides (aOR, 1.45; 95% CI, 1.01-2.09). Significant liver fibrosis was independently predicted by older age (aOR, 1.38; 95% CI, 1.12-1.64) and higher BMI (aOR, 1.14; 95% CI, 1.07-1.23). Extrahepatic diseases were more common in IBD patients with NAFLD compared with those without, namely chronic kidney disease (10.3 vs 2.3%; P < 0.001) and cardiovascular diseases (11.3 vs 4.7%; P = 0.02). Conclusions: NAFLD diagnosed by TE with CAP is a frequent comorbidity in IBD patients and is associated with extrahepatic diseases. Noninvasive screening strategies could help early diagnosis and initiation of interventions, including weight loss, correction of dyslipidemia, and linkage to care. 10.1093/ibd/izy200_video1izy200.video15794817619001.