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Background and Aims: Chronological age often guides the management of patients with inflammatory bowel disease (IBD). Frailty and sarcopenia, which are related but distinct entities that become increasingly prevalent with age, better predict nonsurgical and surgical outcomes in various chronic illnesses. We conducted a systematic review to assess the association between frailty or sarcopenia and adverse nonsurgical outcomes in adult patients with IBD., Methods: Through a systematic literature review of 4 online databases (MEDLINE, EMBASE, Scopus, and CINAHL Plus), we identified 16 studies that focused on frailty or sarcopenia and nonsurgical outcomes in IBD. The Newcastle-Ottawa Scale was used to determine the quality of included studies., Results: We identified 16 studies: 8 frailty-based and 8 sarcopenia-based studies (14 high-quality and 2 low-quality studies). All results were presented in a summarized narrative format. Frailty predicted all hospitalization-related outcomes (hospitalization, readmission, and length of stay) and mortality-related outcomes. The outcomes of therapeutic efficacy, need for therapy escalation, and infections had mixed results in relation to their association with frailty or sarcopenia. The data regarding sarcopenia and hospitalizations were also equivocal., Conclusion: This systematic review supports the use of frailty indices to predict hospitalization- and mortality-related outcomes in adult patients with IBD. Future research should focus on identifying and validating frailty and sarcopenia tools in IBD to better help predict adverse clinical outcomes and response to therapy., (© 2022 The Authors.)

Background and Aims: While there is recent literature to support the discontinuation of 5-aminosalicylate (5-ASA) upon the initiation of biologics, continuing 5-ASA after treatment failure is relatively common. We aimed to assess the impact of concomitant 5-ASA therapy on clinical outcomes in ulcerative colitis (UC) patients escalated to infliximab., Methods: This is a retrospective chart review of patients with moderate-to-severe UC started on infliximab between January 2012 and December 2017 at the University of Alberta. The primary outcome was clinical remission (partial Mayo score < 2) at 6 and 12 months. Secondary outcomes included endoscopic (endoscopic Mayo < 2) and deep remission (combined clinical and endoscopic remission) as well as the need for rescue therapy, hospitalization or colectomy. Univariate and multivariate logistic regression models were used to estimate the odds ratios and 95% CI for the outcomes., Results: One hundred and twenty-one patients were followed over a period of 47 (SD = 34) months. Patients on 5-ASA had increased concomitant immunomodulator use (73.3% vs. 54.1%, p = 0.03). There was no difference in clinical remission at 6 (aOR 2.59, p = 0.07) or 12 months (aOR 0.43, p = 0.06). At 12 months, patients on concomitant 5-ASA were less likely to achieve endoscopic (aOR 0.08, p = 0.01) and deep remission (aOR 0.07, p = 0.02). Adverse outcomes such as need for rescue therapy, hospitalization, and colectomy did not differ between the groups., Conclusions: Our data suggest that 5-ASA may be stopped in patients with moderate-to-severe UC who have been escalated to infliximab therapy as it has no additional benefit to control inflammation., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Standardizing care through pathways has the potential to reduce emergency department (ED) utilization. We developed and evaluated inflammatory bowel disease (IBD) care pathways for that purpose., Methods: Over 2014-2016, IBD patients were retrospectively stratified into those managed and not managed by pathways. Patient data were extracted, and negative binomial regression used to predict the annual number of ED visits., Results: There was a difference of 30.7 ED visits/100 patients between managed and nonmanaged at 12 months ( P < 0.001). The incidence rate ratio of total ED visits occurring annually was 0.750 ( P = 0.008)., Conclusions: Management with IBD care pathways reduces ED utilization., (© The Author(s) 2020. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background & Aims: As more treatment options for inflammatory bowel diseases become available, it is important to identify patients most likely to respond to different therapies. We created and validated a scoring system to identify patients with Crohn's disease (CD) who respond to vedolizumab., Methods: We collected data from the GEMINI 2 phase 3 trial of patients with active CD treated with vedolizumab for 26 weeks (n = 814) and performed logistic regression analysis to identify factors associated with clinical, steroid-free, and durable remission (derivation set). We used these data to develop a clinical decision support tool, which we validated using data from 366 participants in a separate clinical practice observational cohort of patients with active CD treated with vedolizumab for 26 weeks (the VICTORY cohort). We evaluated the ability of this tool to identify patients in clinical remission or corticosteroid-free remission, or those with mucosal healing (MH), clinical remission with MH, or corticosteroid-free remission with MH after vedolizumab therapy using receiver operating characteristic area under the curve (AUC) analyses. The primary outcome was to develop and validate a list of factors associated with achieving remission by vedolizumab in patients with active CD., Results: In the derivation analysis, we identified absence of previous treatment with a tumor necrosis factor antagonist (+3 points), absence of prior bowel surgery (+2 points), absence of prior fistulizing disease (+2 points), baseline level of albumin (+0.4 points per g/L), and baseline concentration of C-reactive protein (reduction of 0.5 points for values between 3.0 and 10.0 mg/L and 3.0 points for values >10.0 mg/L) as factors associated with remission. In the validation set, our model identified patients in clinical remission with an AUC of 0.67, patients in corticosteroid-free remission with an AUC of 0.66, patients with MH with an AUC of 0.72, patients in clinical remission with MH with an AUC of 0.73, and patients in corticosteroid-free clinical remission with MH with an AUC of 0.75. A cutoff value of 13 points identified patients in clinical remission after vedolizumab therapy with 92% sensitivity, patients in corticosteroid-free remission with 94% sensitivity, patients with MH with 98% sensitivity, patients with clinical remission and MH with 100% sensitivity, and patients with corticosteroid-free clinical remission with MH with 100% sensitivity., Conclusions: We developed and validated a scoring system to identify patients with CD most likely to respond to 26 weeks of vedolizumab therapy. Further studies are needed to optimize its accuracy in select populations and determine its cost-effectiveness., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to quantify the safety and effectiveness of vedolizumab (VDZ) when used for UC, and to identify predictors of response to treatment., Methods: Retrospective review (May 2014-December 2016) of VICTORY Consortium data. Adults with follow-up after starting VDZ for clinically active UC were included. Primary effectiveness outcomes were cumulative rates of clinical remission (resolution of all UC-related symptoms) and endoscopic remission (Mayo endoscopic sub-score 0). Key secondary effectiveness outcomes included cumulative rates of corticosteroid-free remission and deep remission (clinical remission and endoscopic remission). Cox proportional hazard analyses were used to identify independent predictors of treatment effectiveness. Non-response imputation (NRI) sensitivity analyses were performed for effectiveness outcomes. Key safety outcomes were rates of serious infection, serious adverse events, and colectomy., Results: We included 321 UC patients (71% prior TNFα antagonist exposure, median follow-up 10 months). The 12-month cumulative rates of clinical remission and endoscopic remission were 51% and 41%, respectively. Corresponding rates for corticosteroid-free remission and deep remission were 37% and 30%, respectively. Using NRI, 12-month rates were 20% (n = 64/321) for clinical remission, 17% (n = 35/203) for endoscopic remission, 15% (n = 30/195) for corticosteroid-free remission, and 14% (n = 28/203) for deep remission. A majority of the patients without adequate follow-up at 12 months who were deemed non-responders using NRI had already achieved clinical remission (n = 70) or a significant clinical response (n = 36) prior to 12 months. VDZ discontinuation prior to 12 months was observed in 91 patients, for lack of response (n = 56), need for surgery (n = 29), or adverse event (n = 6). On multivariable analyses, prior exposure to a TNFα antagonist was associated with a reduced probability of achieving clinical remission (HR 0.53, 95% CI 0.38-0.75) and endoscopic remission (HR 0.51, 95% CI 0.29-0.88). Serious adverse events and serious infections were reported in 6% and 4% of patients, respectively. Overall cumulative rates of colectomy over 12 months were 13%, with lower rates observed in patients naive to TNFα antagonist therapy (2%) than those who had been exposed to TNFα antagonists (19%)., Conclusion: In this large real-world cohort we observed that VDZ was well tolerated and effective in achieving key clinical outcomes.

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disease that is associated with inflammatory bowel disease (IBD) in approximately 70% of cases. Although the pathogenesis is still unknown for both diseases, there is increasing evidence to indicate that they share a common underlying predisposition. Herein, we review the epidemiology, diagnosis, disease pathogenesis, and specific clinical features of the PSC-IBD phenotype. Patients with PSC-IBD have a distinct IBD phenotype with an increased incidence of pancolitis, backwash ileitis, and rectal sparing. Despite often having extensive colonic involvement, these patients present with mild intestinal symptoms or are even asymptomatic, which can delay the diagnosis of IBD. Although the IBD phenotype has been well characterized in PSC patients, the natural history and disease behavior of PSC in PSC-IBD patients is less well defined. There is conflicting evidence regarding the course of IBD in PSC-IBD patients who receive liver transplantation and their risk of recurrent PSC. IBD may also be associated with an increased risk of cholangiocarcinoma in PSC patients. Overall, the PSC-IBD population has an increased risk of developing colorectal neoplasia compared to the conventional IBD population. Lifelong annual surveillance colonoscopy is currently recommended.

Crohn's disease (CD) and ulcerative colitis (UC), the 2 main clinical phenotypes of inflammatory bowel disease (IBD), are diseases that result from a dysregulated immune response to gut microbiota in genetically susceptible hosts. This aberrant immune response may intrinsically predispose IBD patients to infectious complications. Moreover, immunosuppressive medications used to treat IBD including corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, anti-tumor necrosis factor (anti-TNF) agents and other biologics, further increase patients' susceptibility to opportunistic infections. Herpes zoster (HZ), also known as shingles, is an opportunistic viral reactivation often observed in IBD patients with several case reports demonstrating complicated or disseminated disease in those on immunosuppression. While HZ vaccination is recommended in all immunocompetent adults aged ≥60 years, as a live virus vaccine, it is currently contraindicated in IBD patients on anti-TNF therapy and in other significantly immunocompromised patient groups. While caution is still warranted in these circumstances, recent clinical data has emerged which has prompted us to review and examine the universal approach to HZ vaccination in the immunosuppressed IBD population. In the following narrative review, we will discuss and provide an overview of the clinical manifestations, incidence, management and prevention of HZ in the IBD patient.

Objectives: We assessed the real-world effectiveness and safety of vedolizumab (VDZ) in moderate-severe Crohn's disease (CD)., Methods: Retrospective cohort study of seven medical centers, from May 2014 to December 2015. Adults with moderate-severe CD treated with VDZ, with follow-up after initiation of therapy, were included. Using the multivariable Cox proportional hazard analyses, we identified independent predictors of clinical remission or mucosal healing with VDZ. Rates of serious infection (requiring antibiotics, resulting in discontinuation of VDZ, hospitalization or death) and serious adverse events (discontinuation of VDZ, hospitalization or death) were described quantitatively., Results: We included 212 patients with moderate-severe CD (median age 34 years; 40% male; 90% tumor necrosis factor (TNF)-antagonist exposed) with a median follow-up (IQR) of 39 weeks (25-53). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission+mucosal healing) were 35%, 63%, and 26%, respectively. Individuals with prior TNF-antagonist exposure (hazard ratio (HR) 0.40; 95% confidence interval (CI): 0.20-0.81), smoking history (HR 0.47; 95% CI: 0.25-0.89), active perianal disease (HR 0.49; 95% CI: 0.27-0.88), and severe disease activity (HR 0.54; 95% CI: 0.31-0.95) were less likely to achieve clinical remission. Those with prior TNF-antagonist exposure (HR 0.29; 95% CI: 0.12-0.73), and severe disease activity (HR 0.54; 95% CI: 0.31-0.95) were less likely to achieve mucosal healing. During 160 patient years of follow-up (PYF) and 1,433 VDZ infusions, 5 patients developed infusion reactions (3.5 per 1,000 infusions), 21 developed serious infections (13 per 100 PYF), and 17 developed serious adverse events (10 per 100 PYF). A minority of adverse events required discontinuation of therapy (6 per 100 PYF)., Conclusions: VDZ is a safe and effective treatment option for moderate-severe CD in routine practice. Clinical remission and deep remission (clinical remission and mucosal healing) can be achieved in 1/3 of individuals, and a minority of individuals require discontinuation of therapy due to adverse events.

Background: Pulmonary involvement is a recognized extraintestinal complication of inflammatory bowel disease and is associated with airway inflammation. Changes in pulmonary function were previously described as being subclinical. The purpose of this study was to compare pulmonary findings in a large case series of patients with active and quiescent Crohn's disease (CD)., Methods: CD patients, prospectively enrolled between May 2011 and May 2012, completed a demographic questionnaire and Harvey-Bradshaw Index to define disease activity. Each patient also completed blood work, a chest x-ray, pulmonary function testing, respiratory symptom and dyspnea scoring, and a 6-minute walk test. Results are reported as mean ± SE or descriptively as a percent and were analyzed using t tests and chi-square or Fisher's exact tests, respectively. Multivariable linear regression models were built for continuous outcomes and logistic regression models for categorical outcomes., Results: Ninety-five patients (54 remission, 41 active disease), 58.9% males, with a mean age of 41 ± 1 years were enrolled. Patients with active disease compared with those in remission had lower absolute ratios of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) (0.74 ± 0.01 versus 0.77 ± 0.01, P = 0.023), higher degrees of peripheral airway obstruction (34.1% versus 16.7%, P = 0.049), more frequent respiratory symptoms (29.3% versus 9.3%, P = 0.012) and higher Medical Research Council (MRC) dyspnea scales (MRC 2 or 3, 58.5% versus 22.2%, P = 0.001), respectively., Conclusions: CD patients with active disease display clinical pulmonary dysfunction compared with those in remission.