Publications by authors named "Jean-Frederic Colombel"

571 Publications

Rational Combination Therapy to Overcome the Plateau of Drug Efficacy in Inflammatory Bowel Disease.

Gastroenterology 2021 May 4. Epub 2021 May 4.

Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2021.04.068DOI Listing
May 2021

Conjugal inflammatory bowel disease: a systematic review and European survey.

Ann Gastroenterol 2021 26;34(3):361-369. Epub 2021 Feb 26.

Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal (Maria Pia Costa-Santos, Catarina Frias-Gomes, António Oliveira, Joana Torres).

Background: The frequency of inflammatory bowel disease (IBD) is increased after marriage to an individual with the disease. Importantly, the offspring of these couples have a significant risk for developing the disease. Herein, we aimed to better characterize conjugal IBD.

Methods: A systematic literature search was conducted with predetermined search criteria. Relevant manuscripts reporting on couples with IBD and their offspring were selected. Concomitantly, a cross-sectional survey was conducted of couples where both members were affected with IBD, as well as their offspring, and electronically distributed by patients' associations.

Results: We identified 20 reports of IBD in couples, for a total of 68 couples. Of these, 66% were concordant regarding IBD type and 66% were diagnosed after cohabitation. The overall prevalence of IBD in the offspring of these couples was 29%. Our survey identified 58 couples with IBD, with 62% being concordant regarding IBD type; 42.9% were diagnosed prior to cohabitation, in 12.5% one spouse was diagnosed before and the other after cohabitation, and in 44.6% the onset of disease occurred after cohabitation for both. The prevalence of IBD in children born from these couples was 10%. The probability of developing disease in the progeny was 2% at 10 years, 12% at 15 years, and 16% at 20 years of age.

Conclusions: IBD in couples occurs mostly after marriage to an individual with disease or after many years of cohabitation. In a modern cohort, the risk for the progeny was around 16% by the age of 20, lower than previously reported.
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http://dx.doi.org/10.20524/aog.2021.0598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079879PMC
February 2021

Approach to the management of recently diagnosed inflammatory bowel disease patients: a user's guide for adult and pediatric gastroenterologists.

Gastroenterology 2021 Apr 30. Epub 2021 Apr 30.

The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic, progressive, immune-mediated disease of adults and children that has no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in CD, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. While the armamentarium of IBD medications is growing, many patients will not respond to treatment and the selection of first line therapy is critical. Risk stratification of disease severity, based on clinical, demographic and serological markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end-points (treat-to-target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Last, IBD therapy extends far beyond medications, and other aspects of the overall health and well-being of the patient are critical. These include preventive health, nutrition, psycho-behavioral support, addressing patients' concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication.
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http://dx.doi.org/10.1053/j.gastro.2021.04.063DOI Listing
April 2021

Baseline Histological Findings Do Not Predict the Risk of Subsequent Extension in Patients with Limited Ulcerative Colitis.

Dig Dis Sci 2021 May 2. Epub 2021 May 2.

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.

Background: Among patients with limited ulcerative colitis (UC), 30% ultimately extend to pancolitis and are at increased risk of adverse clinical outcomes. Risk of endoscopic extension has been found to correlate with clinical features such as early age of onset.

Aims: We sought to determine whether histologic features correlate with disease extension.

Methods: The study population consisted of 40 patients with UC from two large academic centers diagnosed between 2006 and 2017. Eligible cases had a diagnosis of endoscopically limited UC (Montreal E1 or E2) at baseline and ≥ 2 subsequent endoscopic examinations with biopsies. Severity of inflammation was scored using both the Mount Sinai Activity Index and Nancy Histological Index.

Results: Patients were divided into two cohorts: those who progressed to pancolitis (Montreal E3) were defined as "Extenders" (n = 21), whereas "Non-extenders" (n = 19) were cases without progression in the follow-up period. The median follow-up time was 58.4 months. The histologic scores in the endoscopically involved mucosa of the index biopsies were not associated with subsequent extension of disease, overall. However, among extender cohort, the index histology scores correlated with biopsy scores at extension (r = 0.455, P = 0.044) and index severity was associated with a shorter time to extension (r =  - 0.611, P = 0.003). Furthermore, female patients had a shorter time to extension (P = 0.013).

Conclusions: Histological severity of limited UC is not an independent predictor of extension in UC. However, among patients who subsequently extend, severe inflammation at baseline correlates with shorter progression time and severe inflammation when extension occurs. Patients with limited UC but severe histologic inflammation may warrant more frequent endoscopic surveillance.
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http://dx.doi.org/10.1007/s10620-021-06970-yDOI Listing
May 2021

Risk of Postpartum Flare Hospitalizations in Patients with Inflammatory Bowel Disease Persists After Six Months.

Dig Dis Sci 2021 May 1. Epub 2021 May 1.

Department of Medicine, Henry D. Janowitz Division of Gastroenterology, Mount Sinai Hospital, 1468 Madison Ave, Annenberg RM 5-12, New York, NY, 10029, USA.

Background: Although patients with IBD are at higher risk for flares during the postpartum period, little is known about the risk factors, timeline, and healthcare-associated costs of a readmission flare.

Aims: To ascertain the timeline in which patients are hospitalized for postpartum inflammatory bowel disease (IBD) flares, and the associated risk factors.

Methods: This is a nationwide retrospective cohort study of 7054 patients with IBD who delivered between 2010-2014 obtained from the National Readmissions Database. The presence of IBD was defined using previously validated International Classification of Diseases codes, and univariable and multivariable regression models were performed to assess risk factors associated with a postpartum flare hospitalization over the nine-month observation period.

Results: A total of 353 (5.0%) patients were hospitalized for a postpartum IBD flare, with approximately one-third (30.0%) readmitted after 6 months. On multivariable analysis, having Crohn's disease (aRR 1.47, 95%CI 1.16-1.88), Medicare insurance (aRR 3.30, 95%CI 2.16-5.02), and ≥ 2 comorbidities (aRR 1.34, 95%CI 1.03-1.74) were independently associated with a higher risk of an IBD flare hospitalization. Compared to patients aged 25-29, those 20-24 were at higher risk for an IBD flare readmission (aRR 1.58, 95%CI 1.17-2.13), whereas patients aged 35-39 years were at lower risk (aRR 0.63, 95%CI 0.43-0.92).

Conclusions: Among patients with IBD, Crohn's disease, Medicare insurance, multiple comorbidities, and younger age were independent risk factors for a postpartum IBD flare hospitalization. As approximately one-third of these readmissions occurred after 6 months, it is imperative to ensure adequate follow-up and treatment for postpartum IBD patients, particularly in the extended postpartum period.
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http://dx.doi.org/10.1007/s10620-021-06999-zDOI Listing
May 2021

A Pilot Clinical Study on Post-Operative Recurrence Provides Biological Clues for a Role of Yeasts and Fluconazole in Crohn's Disease.

J Fungi (Basel) 2021 Apr 22;7(5). Epub 2021 Apr 22.

INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France.

Background And Aims: This study prompted by growing evidence of the relationship between the yeast and Crohn's disease (CD) was intended to assess the effect of a 6-month course of the antifungal fluconazole (FCZ) on post-operative recurrence of CD.

Methods: Mycological samples (mouth swabs and stools) and serum samples were collected from 28 CD patients randomized to receive either FCZ ( = 14) or placebo ( = 14) before surgical resection. Serological analysis focused on levels of calprotectin, anti-glycan antibodies, and antibody markers of pathogenic transition. Levels of galectin-3 and mannose binding lectin (MBL) involved in sensing and inflammation were also measured.

Results: 1, 2, 3, and 6 months after surgery, endoscopy revealed recurrence in 5/12 (41.7%) patients in the FCZ group and 5/9 (55.6%) in the placebo group, the small cohort preventing any clinical conclusions. In both groups, surgery was followed by a marked decrease in colonization and biomarkers of pathogenic transition decreased to non-significant levels. Anti-glycan antibodies also decreased but remained significant for CD. Galectin-3 and calprotectin also decreased. Conversely, MBL levels, which inversely correlated with anti- antibodies before surgery, remained stable. Building biostatistical multivariate models to analyze he changes in antibody and lectin levels revealed a significant relationship between and CD.

Conclusion: Several combinations of biomarkers of adaptive and innate immunity targeting were predictive of CD recurrence after surgery, with area under the curves (AUCs) as high as 0.86. FCZ had a positive effect on biomarkers evolution. ClinicalTrials.gov ID: NCT02997059, 19 December 2016. University Hospital Lille, Ministry of Health, France. Effect of Fluconazole on the Levels of Anti- Antibodies (ASCA) After Surgical Resection for Crohn's Disease. Multicenter, Randomized, and Controlled in Two Parallel Groups Versus Placebo.
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http://dx.doi.org/10.3390/jof7050324DOI Listing
April 2021

Aging and IBD: A New Challenge for Clinicians and Researchers.

Inflamm Bowel Dis 2021 Apr 27. Epub 2021 Apr 27.

Department of Medicine, Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Evidence from recent epidemiological data suggests that the patient population with inflammatory bowel disease (IBD) is chronologically aging. As these individuals become older, cellular senescence leads to a state of chronic inflammation. This process, known as inflammaging, is thought to be closely linked with biological aging and may be upregulated within IBD. As a consequence, we see an increased risk of aging-related disorders within IBD. In addition, we see that frailty, which results from physiologic decline, is increasing in prevalence and is associated with adverse clinical outcomes in IBD. As such, in this review we explore the potential overlapping biology of IBD and aging, discuss the risk of aging-related disorders in IBD, and describe frailty and its relation to clinical outcomes within IBD. Finally, we discuss current considerations for clinical care and potential research avenues for further investigation.
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http://dx.doi.org/10.1093/ibd/izab039DOI Listing
April 2021

Serological response to mRNA COVID-19 vaccines in IBD patients receiving biological therapies.

Gastroenterology 2021 Apr 19. Epub 2021 Apr 19.

Skirball Institute of Biomolecular Medicine, Department of Microbiology, Division of Gastroenterology and Hepatology, Department of Medicine, New York University School of Medicine, New York, New York.

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http://dx.doi.org/10.1053/j.gastro.2021.04.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055494PMC
April 2021

The impact of vedolizumab on COVID-19 outcomes among adult IBD patients in the SECURE-IBD registry.

J Crohns Colitis 2021 Apr 22. Epub 2021 Apr 22.

The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY.

Introduction: The impact of immune-modifying therapies on outcomes of Coronavirus disease of 2019 (COVID-19) is variable. The purpose of this study was to determine the impact of vedolizumab (VDZ), a gut-selective anti-integrin, on COVID-19 outcomes in inflammatory bowel disease (IBD) patients.

Methods: Using data from the Surveillance of Coronavirus Under Research Exclusion for IBD (SECURE-IBD), an international registry of IBD patients with confirmed COVID-19, we studied the impact of VDZ on COVID-19 hospitalization and severe COVID-19 (intensive care unit stay, mechanical ventilation and/or death).

Results: Of 3,647 adult patients on any IBD medication in the registry, 457 (12.5%) patients were on VDZ. On multivariable analyses using backward selection of covariates, VDZ use was not associated with hospitalization or severe COVID-19 when comparing to patients on all other medications [adjusted odds ratio (aOR) 0.87; 95% confidence interval (CI) 0.71, 1.1 and aOR 0.95; 95% CI 0.53; 1.73, respectively]. On comparing VDZ monotherapy to anti-TNF monotherapy, the odds for hospitalization, but not severe COVID-19, were higher (aOR CI 1.39; 95% CI 1.001, 1.90 and aOR 2.92; 95% CI 0.98, 8.71, respectively). In an exploratory analysis, VDZ monotherapy, compared to anti-TNF monotherapy, was associated with new-onset GI symptoms at the time of COVID-19, especially among patients whose IBD was in remission.

Conclusions: COVID-19 outcomes among IBD patients on VDZ are comparable to those on all other therapies. Hospitalization, but not severe COVID-19, is more likely with VDZ monotherapy than with anti-TNF monotherapy. Overall, VDZ appears to be safe in IBD patients with COVID-19.
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http://dx.doi.org/10.1093/ecco-jcc/jjab071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083188PMC
April 2021

The role of gastrointestinal pathogens in inflammatory bowel disease: a systematic review.

Therap Adv Gastroenterol 2021 31;14:17562848211004493. Epub 2021 Mar 31.

Section of Gastroenterology, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN.

The inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, progressive, inflammatory conditions of the gastrointestinal tract. Imbalance in the gut microbial community, or dysbiosis, and the subsequent immune response, represent the critical relationship between genetic susceptibility, microbes, and environment factors, that result in IBD. Gastrointestinal pathogens - a common cause of dysbiosis - have been implicated as an environmental trigger in new onset IBD, as well as flare of existing IBD. In this article, we systematically review clinical data regarding the association between specific gastrointestinal pathogens and IBD. Numerous bacteria, viruses, fungi, and parasites have been implicated in the pathogenesis of IBD, and exacerbations of existing disease. In this article, we will also specifically discuss the less recognized microbes that have an inverse association with IBD, including certain bacterial pathogens, such as , and parasites, such as species. Future prospective and experimental studies are required to establish causality and clarify potential mechanisms of enteric pathogens in modifying the risk and course of IBD.
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http://dx.doi.org/10.1177/17562848211004493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020742PMC
March 2021

Reply.

Clin Gastroenterol Hepatol 2021 Apr 8. Epub 2021 Apr 8.

Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

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http://dx.doi.org/10.1016/j.cgh.2021.04.010DOI Listing
April 2021

Comparative Efficacy and Rapidity of Action for Infliximab Vs Ustekinumab in Biologic Naïve Crohn's Disease.

Clin Gastroenterol Hepatol 2021 Apr 7. Epub 2021 Apr 7.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background & Aims: Comparative effectiveness has become increasingly important to help position therapies for inflammatory bowel disease. We compared the efficacy and rapidity of onset of action of infliximab vs ustekinumab induction therapy for moderate to severe biologic-naïve Crohn's disease (CD) using patient-level data from randomized controlled trials.

Methods: This was a post hoc analysis of 2 large CD clinical trial programs that included data on 420 biologic-naïve CD patients. Differences in proportions of patients achieving week 6 clinical remission, clinical response, and normalization of calprotectin were compared. Multivariate logistic regression was used to adjust for confounders. Sensitivity analysis was conducted using propensity scores to create a cohort of matched participants with similar distribution of baseline covariates.

Results: At week 6, a comparable number of patients achieved clinical remission with infliximab compared with patients treated with ustekinumab (44.9% vs 37.9%; adjusted odds ratio [aOR], 1.22; 95% CI, 0.79-1.89). Similarly, at week 6 the clinical response rates were not significantly different (58.4% infliximab vs 54.9% ustekinumab; aOR, 1.25; 95% CI, 0.82-1.90). No significant difference was observed between treatment groups for achieving a week 6 fecal calprotectin level less than 250 mcg/L in those with increased values at baseline (42.3% infliximab vs 34.7% ustekinumab; aOR, 1.34; 95% CI, 0.79-2.28). Similar results were seen for all analyses performed within the propensity matched cohort.

Conclusions: Based on this post hoc analysis, infliximab and ustekinumab appear to have similar efficacy and speed of onset in patients with CD who are biologic-naïve.
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http://dx.doi.org/10.1016/j.cgh.2021.04.006DOI Listing
April 2021

Improved Smoking Cessation Rates in a Pharmacist-Led Program Embedded in an Inflammatory Bowel Disease Specialty Medical Home.

J Pharm Pract 2021 Apr 8:8971900211000682. Epub 2021 Apr 8.

Mount Sinai Hospital, New York, NY, USA.

Background: Cigarette smoking is associated with disease progression, poor outcomes, and increased biologic use in Crohn's Disease (CD). In this prospective study, we describe the structure and results of a pharmacist-driven smoking cessation program in an Inflammatory Bowel Disease (IBD) Specialty Medical Home.

Methods: One pharmacist designed and implemented a collaborative drug therapy management (CDTM) program, which allowed the pharmacist to initiate and modify smoking cessation aids, monitor medication safety and efficacy, and provide behavioral counseling. Crohn's Disease patients who were current smokers and referred to the program were analyzed. Clinical and demographic data, disease activity, and smoking history were collected. The primary outcome was the proportion of patients in the enrolled group and the declined group who quit smoking at least once during the follow-up period. Secondary outcomes include demographic and clinical differences between enrolled and declined patients, and enrolled quitters and non-quitters.

Results: Thirty-two patients were referred to the program and 19 participated. Over a median follow-up period of 305 [264-499] days, 42% (8/19) of enrolled patients quit smoking at least once. Fifteen percent (2/13) of declined patients quit smoking. Patients who continued to smoke had more instances of loss of response to a biologic, need to start a new biologic, or escalation of biologic therapy. The CDTM pharmacist was able to provide all necessary clinical services for smokers enrolled in the program.

Conclusions: A pharmacist-led smoking cessation program in a specialty medical home is feasible. It may result in successful quit attempts and may optimize IBD medication use.
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http://dx.doi.org/10.1177/08971900211000682DOI Listing
April 2021

Deep Analysis of the Peripheral Immune System in IBD Reveals New Insight in Disease Subtyping and Response to Monotherapy or Combination Therapy.

Cell Mol Gastroenterol Hepatol 2021 Apr 2. Epub 2021 Apr 2.

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background: Inflammatory bowel disease (IBD) is a complex disease with variable presentation, progression, and response to therapies. Current disease classification is based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, and thus we measured 39 circulating immune cell types in a large cohort of IBD and control subjects and performed immunotype:phenotype associations.

Methods: We performed fluorescence-activated cell sorting or CyTOF analysis on blood from 728 Crohn's disease, 464 ulcerative colitis, and 334 non-IBD patients, with available demographics, endoscopic and clinical examinations and medication use.

Results: We observed few immune cell types commonly affected in IBD (lowered natural killer cells, B cells, and CD45RA CD8 T cells). Generally, the immunophenome was distinct between ulcerative colitis and Crohn's disease. Within disease subtype, there were further distinctions, with specific immune cell types associating with disease duration, behavior, and location. Thiopurine monotherapy altered abundance of many cell types, often in the same direction as disease association, while anti-tumor necrosis factor (anti-TNF) monotherapy demonstrated an opposing pattern. Concomitant use of an anti-TNF and thiopurine was not synergistic, but rather was additive. For example, thiopurine monotherapy use alone or in combination with anti-TNF was associated with a dramatic reduction in major subclasses of B cells.

Conclusions: We present a peripheral map of immune cell changes in IBD related to disease entity and therapies as a resource for hypothesis generation. We propose the changes in B cell subsets could affect antibody formation and potentially explain the mechanism behind the superiority of combination therapy through the impact of thiopurines on pharmacokinetics of anti-TNFs.
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http://dx.doi.org/10.1016/j.jcmgh.2021.03.012DOI Listing
April 2021

Predicting endoscopic remission in Crohn's disease by the modified multiplier SES-CD (MM-SES-CD).

Gut 2021 Mar 25. Epub 2021 Mar 25.

Department of Medicine (Division of Gastroenterology), University of California San Diego School of Medicine, La Jolla, California, USA.

Background And Aims: The Simple Endoscopic Score for Crohn's disease (SES-CD) is the primary tool for measurement of mucosal inflammation in clinical trials but lacks prognostic potential. We set to develop and validate a modified multiplier of the SES-CD (MM-SES-CD), which takes into consideration each individual parameter's prognostic value for achieving endoscopic remission (ER) while on active therapy.

Methods: In this posthoc analysis of three CD clinical trial programmes (n=350 patients, baseline SES-CD ≥ 3 with confirmed ulceration), data were pooled and randomly split into a 70% training and 30% testing cohort. The MM-SES-CD was designed using weights for individual parameters as determined by logistic regression modelling, with 1-year ER (SES-CD < 3) being the dependent variable. A cut point score for low and high probability of ER was determined by using the maximum Youden Index and validated in the testing cohort.

Results: Baseline ulcer size, extent of ulceration and presence of non-passable strictures had the strongest association with 1-year ER as compared with affected surface area, with differential weighting of individual parameters across disease segments being observed during logistic regression. The MM-SES-CD was generated using this weighted regression model and demonstrated strong discrimination for ER in the training dataset (area under the receiver operator curve (AUC) 0.83, 95% CI 0.78 to 0.94) and in the testing dataset (AUC 0.82, 95% CI 0.77 to 0.92). In comparison to the MM-SES-CD scoring model, the original SES-CD score lacks accuracy (AUC 0.60, 95% CI 0.55 to 0.65) for predicting the achievement of ER.

Conclusions: We developed and internally validated the MM-SES-CD as an endoscopic severity assessment tool to predict one-year ER in patients with CD on active therapy.
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http://dx.doi.org/10.1136/gutjnl-2020-323799DOI Listing
March 2021

The Chicago Classification of Pouchitis: An Important Step Toward a Needed Consensus.

Clin Gastroenterol Hepatol 2021 Mar 19. Epub 2021 Mar 19.

The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

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http://dx.doi.org/10.1016/j.cgh.2021.03.025DOI Listing
March 2021

Results of the Seventh Scientific Workshop of ECCO: Precision medicine in IBD- prediction and prevention of inflammatory bowel disease.

J Crohns Colitis 2021 Mar 17. Epub 2021 Mar 17.

Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland.

Inflammatory bowel disease [IBD] is a complex chronic disorder with no clear aetiology and no known cure. Despite recent advances in overall disease management and improved therapeutics, patients with IBD still experience a substantial burden. Furthermore, as the incidence continues to increase in developing areas of the world, it is expected that the burden of IBD to society will increase and exert tremendous pressure on healthcare systems worldwide. Therefore, new strategies to prevent the global increase of IBD are urgently required. Data are being progressively acquired on the period preceding disease diagnosis, which support the concept that IBD has a preclinical period that may reveal the triggers of disease and may be amenable to early intervention. Having a better knowledge of this preclinical period will increase the potential not only for improved understanding of disease pathogenesis and improved therapeutics, but also for disease prediction and prevention.
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http://dx.doi.org/10.1093/ecco-jcc/jjab048DOI Listing
March 2021

SARS-CoV-2 vaccination in IBD: past lessons, current evidence and future challenges.

J Crohns Colitis 2021 Mar 15. Epub 2021 Mar 15.

The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.

Since the beginning of the pandemic, patients with inflammatory bowel diseases (IBD) have been considered at high-risk for infection and complications of COVID-19. However, IBD patients and patients taking immunosuppressive therapy were excluded from clinical phase III vaccine trials, complicating the assessment of effectiveness of these new vaccines. From past experience we know that adapted vaccination strategies may be appropriate in some IBD patients to optimize immunogenicity. We review current evidence on SARS-CoV-2 vaccination relevant to IBD patients, including immune responses from humoral to cellular, emerging data on new variants and off-label vaccination schemes. We also identify clinical and scientific knowledge gaps that can be translated into both large-scale population-based studies and targeted vaccine studies to describe the precise immune responses induced by SARS-CoV-2 vaccines in IBD patients. We strongly endorse the recommendation of vaccinating IBD patients to ensure maximal protection from COVID-19 both for the individual and the community.
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http://dx.doi.org/10.1093/ecco-jcc/jjab046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989537PMC
March 2021

Outcomes of Passable and Non-Passable Strictures in Clinical Trials of Crohn's Disease: A Post-hoc Analysis.

J Crohns Colitis 2021 Mar 6. Epub 2021 Mar 6.

Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria.

Background And Aims: There is paucity of evidence on the reversibility of Crohn's disease (CD) related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures.

Methods: This was a post-hoc analysis of three large CD clinical trial programs examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the SES-CD. The impact of non-passable strictures on achieving clinical remission (CR) and endoscopic remission (ER) was assessed using multivariate logistic regression models. CR was defined as CDAI<150, clinical response as CDAI reduction of >100 points, and ER as SES-CD score < 3.

Results: After one year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared to those with passable or no strictures, with reduced odds of one-year CR (adjusted odds ratio (aOR) 0.17, 95%CI 0.03-0.99, p=0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER (aOR 0.82, 95%CI 0.23-2.85, p=0.751) at one year.

Conclusions: Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although are less likely to obtain CR compared to patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.
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http://dx.doi.org/10.1093/ecco-jcc/jjab045DOI Listing
March 2021

Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms.

Gastroenterology 2021 Mar 4. Epub 2021 Mar 4.

Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Catalan Institute for Research and Advanced Studies, Barcelona, Spain.

Background & Aims: Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance.

Methods: Human intestinal biopsy tissues were obtained from patients with COVID-19 (n =19) and uninfected control individuals (n = 10) for microscopic examination, cytometry by time of flight analyses, and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients in the United States (n = 634) and Europe (n = 287) using multivariate logistic regressions.

Results: COVID-19 case patients and control individuals in the biopsy cohort were comparable for age, sex, rates of hospitalization, and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 14 of 16 patients studied. High-dimensional analyses of GI tissues showed low levels of inflammation, including down-regulation of key inflammatory genes including IFNG, CXCL8, CXCL2, and IL1B and reduced frequencies of proinflammatory dendritic cells compared with control individuals. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of sex, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms.

Conclusions: These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in patients with COVID-19 presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2-associated inflammation needs to be further examined.
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http://dx.doi.org/10.1053/j.gastro.2021.02.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931673PMC
March 2021

Five-Year Efficacy and Safety of Ustekinumab Treatment in Crohn's Disease: The IM-UNITI Trial.

Clin Gastroenterol Hepatol 2021 Feb 19. Epub 2021 Feb 19.

Janssen Research & Development, LLC, Spring House, Pennsylvania.

Background & Aims: The IM-UNITI study and long-term extension (LTE) evaluated the long-term efficacy, safety, and immunogenicity of subcutaneous ustekinumab maintenance therapy in patients with Crohn's disease. Here, we report the final results of IM-UNITI LTE through 5 years.

Methods: Patients completing safety and efficacy evaluations at week 44 of the maintenance study were eligible to participate in the LTE and continue the treatment they were receiving. Unblinding occurred after completion of maintenance study analyses (August 2015), and patients receiving placebo were discontinued. No dose adjustment occurred in the LTE. Efficacy assessments were conducted every 12 weeks until unblinding and at dosing visits thereafter through week 252. Serum ustekinumab concentrations and antidrug antibodies were evaluated through weeks 252 and 272, respectively.

Results: Using an intent-to-treat analysis of all patients randomized to ustekinumab at maintenance baseline, 34.4% of patients in the every-8-weeks group and 28.7% in the every-12-weeks group were in clinical remission at week 252. Corresponding remission rates among patients who entered the LTE were 54.9% and 45.2%. Overall, adverse event rates (per 100 patient-years) from maintenance week 0 through the final visit generally were similar in the placebo and combined ustekinumab groups for all adverse events (440.3 vs 327.6), serious adverse events (19.3 vs 17.5), infections (99.8 vs 93.8), and serious infections (3.9 vs 3.4). Serum ustekinumab concentrations were maintained throughout the LTE. Antidrug antibodies occurred in 5.8% of patients who received ustekinumab during induction and maintenance and continued in the LTE.

Conclusions: Patients receiving subcutaneous ustekinumab maintained clinical remission through 5 years. No new safety signals were observed. ClinicalTrials.gov number NCT01369355.
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http://dx.doi.org/10.1016/j.cgh.2021.02.025DOI Listing
February 2021

Prevalence and progression of incidental terminal ileitis on non-diagnostic colonoscopy: a systematic review and meta-analysis.

J Crohns Colitis 2021 Feb 14. Epub 2021 Feb 14.

The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY.

Background: Incidentally-diagnosed terminal ileitis (IDTI) has been reported among asymptomatic persons undergoing non-diagnostic colonoscopy. The purpose of our study was to determine the prevalence and long-term outcomes of asymptomatic terminal ileitis.

Methods: We performed a systematic review using three biomedical databases (Medline, Embase and Web of Science) and relevant scientific meeting abstracts. We identified observational studies that reported the prevalence of IDTI in adults undergoing screening or polyp surveillance colonoscopy and/or the long-term outcomes of such lesions. A random-effects meta-analysis was conducted to determine the pooled prevalence rate of IDTI. The progression of IDTI to overt Crohn's disease (CD) was also described.

Results: Of 2,388 eligible studies, 1,784 were screened after excluding duplicates, 84 were reviewed in full text, and 14 studies were eligible for inclusion. Seven studies reported the prevalence of IDTI in 44,398 persons undergoing non-diagnostic colonoscopy, six studies reported follow-up data, and one study reported both types of data. The pooled prevalence rate of IDTI was 1.6% (CI 0.1-21.8%) with significant heterogeneity (I 2 = 99.7). Among patients who had undergone non-diagnostic colonoscopy and had follow-up data (range 13-84 months reported in five studies), progression to overt CD was rare.

Conclusion: IDTI is not uncommon on non-diagnostic colonoscopies. Based on limited data, the rate of its progression to overt CD seems low, and watchful waiting is likely a reasonable strategy. Further long-term follow-up studies are needed to inform the natural history of incidental terminal ileitis, factors that predict progression to CD, and therapeutic implications.
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http://dx.doi.org/10.1093/ecco-jcc/jjab030DOI Listing
February 2021

Colectomy Incidence Rates in Five-Year Data From the Observational Postmarketing Ulcerative Colitis Study of Originator Infliximab.

Inflamm Bowel Dis 2021 Feb 12. Epub 2021 Feb 12.

Universitätsklinik für Innere Medizin III, Vienna, Austria.

Background: This analysis of the Observational Postmarketing Ulcerative Colitis Study examined incidence rates of colectomy in patients with ulcerative colitis who received originator infliximab (IFX) or conventional therapies (ConvRx) as per their treating physician.

Methods: Cox proportional hazards models compared time to colectomy for both treatment groups. A secondary analysis examined colectomy incidence rates based on IFX exposure timing (defined by a 90-day window after the last IFX dose date).

Results: Of 2239 patients with data, 1059 enrolled in IFX and 1180 enrolled in ConvRx (including 296 patients who switched to IFX). Patients in the IFX group had more severe disease at baseline vs the ConvRx group (percentage with baseline partial Mayo score 7-9: 46.0% vs 30.5%, respectively). During 5 years of follow-up, 271 patients (12.1% of enrolled patients) had colectomy. Enrollment in the IFX group was associated with a higher risk of colectomy (hazard ratio = 3.12; 95% confidence interval, 2.25-4.34; P < 0.001) compared with enrollment in the ConvRx group. A total of 174 colectomies occurred in the IFX group, but 97 of these colectomies occurred ≥90 days after the last IFX dose date.

Conclusions: Colectomy was reported at a higher rate in the IFX group than in the ConvRx group, although patients in the IFX group had more severe disease at baseline and most of the colectomies occurred after patients had been off of IFX for ≥90 days.
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http://dx.doi.org/10.1093/ibd/izab026DOI Listing
February 2021

Autoimmune and Chronic Inflammatory Disease Patients with COVID-19.

ACR Open Rheumatol 2021 Feb 1;3(2):111-115. Epub 2021 Feb 1.

Icahn School of Medicine at Mount Sinai, New York, New York.

Objective: There are limited data on the impact of coronavirus disease 2019 (COVID-19) on hospitalized patients with autoimmune and chronic inflammatory disease (AICID) compared with patients who do not have AICID. We sought to evaluate whether patients with AICID who have confirmed COVID-19 presenting to the hospital are at higher risk of adverse outcomes compared with those patients without AICID who are infected with COVID-19 and whether immunosuppressive medications impact this risk.

Methods: We performed a multicenter retrospective cohort study with patients presenting to five hospitals in a large academic health system with polymerase chain reaction-confirmed COVID-19 infection. We evaluated the impact of having an AICID and class of immunosuppressive medication being used to treat patients with AICID (biologics, nonbiologic immunosuppressives, or systemic corticosteroids) on the risk of developing severe COVID-19 defined as requiring mechanical ventilation (MV) and/or death.

Results: A total of 6792 patients with confirmed COVID-19 were included in the study, with 159 (2.3%) having at least one AICID. On multivariable analysis, AICIDs were not significantly associated with severe COVID-19 (adjusted odds ratio [aOR] 1.3, 95% confidence interval [CI]: 0.9-1.8). Among patients with AICID, use of biologics or nonbiologic immunosuppressives did not increase the risk of severe COVID-19. In contrast, systemic corticosteroid use was significantly associated with an increased risk of severe COVID-19 (aOR 6.8, 95% CI: 2.5-18.4).

Conclusion: Patients with AICID are not at increased risk of severe COVID-19 with the exception of those on corticosteroids. These data suggest that patients with AICID should continue on biologic and nonbiologic immunosuppression but limit steroids during the COVID-19 pandemic.
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http://dx.doi.org/10.1002/acr2.11221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882518PMC
February 2021

Development and validation of multivariable prediction models for adverse COVID-19 outcomes in IBD patients.

medRxiv 2021 Jan 20. Epub 2021 Jan 20.

Importance: Risk calculators can facilitate shared medical decision-making . Demographics, comorbidities, medication use, geographic region, and other factors may increase the risk for COVID-19-related complications among patients with IBD .

Objectives: Develop an individualized prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with IBD.

Design Setting And Participants: This study developed and validated prognostic penalized logistic regression models using reports to Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) from March-October 2020. Model development was done using a training data set (85% of cases reported March 13 - September 15, 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported September 16-October 20, 2020).

Main Outcomes And Measures: COVID-19 related:Hospitalization+: composite outcome of hospitalization, ICU admission, mechanical ventilation, or deathICU+: composite outcome of ICU admission, mechanical ventilation, or deathDeathWe assessed the resulting models' discrimination using the area under the curve (AUC) of the receiver-operator characteristic (ROC) curves and reported the corresponding 95% confidence intervals (CIs).

Results: We included 2709 cases from 59 countries (mean age 41.2 years [s.d. 18], 50.2% male). A total of 633 (24%) were hospitalized, 137 (5%) were admitted to the ICU or intubated, and 69 (3%) died. 2009 patients comprised the training set and 700 the test set.The models demonstrated excellent discrimination, with a test set AUC (95% CI) of 0.79 (0.75, 0.83) for Hospitalization+, 0.88 (0.82, 0.95) for ICU+, and 0.94 (0.89, 0.99) for Death. Age, comorbidities, corticosteroid use, and male gender were associated with higher risk of death, while use of biologic therapies was associated with a lower risk.

Conclusions And Relevance: Prognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of IBD patients. A free online risk calculator ( https://covidibd.org/covid-19-risk-calculator/ ) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with IBD patients. The tool numerically and visually summarizes the patient's probabilities of adverse outcomes and associated CIs. Helping physicians identify their highest-risk patients will be important in the coming months as cases rise in the US and worldwide. This tool can also serve as a model for risk stratification in other chronic diseases.

Key Points: How well can a multivariable risk model predict the risk of hospitalization, intensive care unit (ICU) stay, or death due to COVID-19 in patients with inflammatory bowel disease (IBD)? Multivariable prediction models developed using data from an international voluntary registry of IBD patients and available for use online ( https://covidibd.org/ ) have very good discrimination for predicting hospitalization (Test set AUC 0.79) and excellent discrimination for ICU admission (Test set AUC 0.88) and death (Test set AUC 0.94). The models were developed with a training sample of 2009 cases and validated in an independent test sample of 700 cases comprised of a random sub-sample of cases and all cases entered in the registry during a one-month period after model development. This risk prediction model may serve as an effective tool for healthcare providers to facilitate conversations about COVID-19-related risks with IBD patients.
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http://dx.doi.org/10.1101/2021.01.15.21249889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836127PMC
January 2021

Reply.

Gastroenterology 2021 Apr 13;160(5):1886-1887. Epub 2021 Jan 13.

University of North Carolina Department of Pediatric Gastroenterology, Chapel Hill, North Carolina.

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http://dx.doi.org/10.1053/j.gastro.2021.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831798PMC
April 2021

COVID-19 and Inflammatory Bowel Disease: Lessons Learned, Practical Recommendations, and Unanswered Questions.

Gastroenterology 2021 04 30;160(5):1447-1451. Epub 2020 Dec 30.

The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

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http://dx.doi.org/10.1053/j.gastro.2020.12.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832021PMC
April 2021

Increasing Prevalence of Frailty and Its Association with Readmission and Mortality Among Hospitalized Patients with IBD.

Dig Dis Sci 2021 Jan 1. Epub 2021 Jan 1.

Department of Medicine, Division of Digestive and Liver Diseases, Columbia University Medical Center, 1468 Madison Ave, Annenberg RM 5-12, New York, NY, 100329, USA.

Background: Although age is often used as a clinical risk stratification tool, recent data have suggested that adverse outcomes are driven by frailty rather than chronological age.

Aims: In this nationwide cohort study, we assessed the prevalence of frailty, and factors associated with 30-day readmission and mortality among hospitalized IBD patients.

Methods: Using the Nationwide Readmission Database, we examined all patients with IBD hospitalized from 2010 to 2014. Based on index admission, we defined IBD and frailty using previously validated ICD codes. We used univariable and multivariable regression to assess risk factors associated with all-cause 30-day readmission and 30-day readmission mortality.

Results: From 2010 to 2014, 1,405,529 IBD index admissions were identified, with 152,974 (10.9%) categorized as frail. Over this time period, the prevalence of frailty increased each year from 10.20% (27,594) in 2010 to 11.45% (33,507) in 2014. On multivariable analysis, frailty was an independent predictor of readmission (aRR 1.16, 95% CI: 1.14-1.17), as well as readmission mortality (aRR 1.12, 95% CI 1.02-1.23) after adjusting for relevant clinical factors. Frailty also remained associated with readmission after stratification by IBD subtype, admission characteristics (surgical vs. non-surgical), age (patients ≥ 60 years old), and when excluding malnutrition, weight loss, and fecal incontinence as frailty indicators. Conversely, we found older age to be associated with a lower risk of readmission.

Conclusions: Frailty, independent of age, comorbidities, and severity of admission, is associated with a higher risk of readmission and mortality among IBD patients, and is increasing in prevalence. Given frailty is a potentially modifiable risk factor, future studies prospectively assessing frailty within the IBD patient population are needed.
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http://dx.doi.org/10.1007/s10620-020-06746-wDOI Listing
January 2021

STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD.

Gastroenterology 2021 Apr 19;160(5):1570-1583. Epub 2021 Feb 19.

Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt/Main, Germany. Electronic address:

Background: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD.

Methods: Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale.

Results: In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth.

Conclusions: STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.
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http://dx.doi.org/10.1053/j.gastro.2020.12.031DOI Listing
April 2021