Publications by authors named "Luc Biedermann"

136 Publications

Systematic Review of Outcome Measures Used in Observational Studies of Adults with Eosinophilic Esophagitis.

Int Arch Allergy Immunol 2021 Sep 20:1-25. Epub 2021 Sep 20.

Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Background: Over the last 20 years, diverse outcome measures have been used to evaluate the effectiveness of therapies for eosinophilic esophagitis (EoE). This systematic review aims to identify the readouts used in observational studies of topical corticosteroids, diet, and dilation in adult EoE patients.

Methods: We searched MEDLINE and Embase for prospective and retrospective studies (cohorts/case series, randomized open-label, and case-control) evaluating the use of diets, dilation, and topical corticosteroids in adults with EoE. Two authors independently assessed the articles and extracted information about histologic, endoscopic, and patient-reported outcomes and tools used to assess treatment effects.

Results: We included 69 studies that met inclusion criteria. EoE-associated endoscopic findings (assessed either as absence/presence or using Endoscopic Reference Score) were evaluated in 24/35, 11/17, and 9/17 studies of topical corticosteroids, diet, and dilation, respectively. Esophageal eosinophil density was recorded in 32/35, 17/17, and 11/17 studies of topical corticosteroids, diet, and dilation, respectively. Patient-reported outcomes were not uniformly used (only in 14, 8, and 3 studies of topical corticosteroids, diet, and dilation, respectively), and most tools were not validated for use in adults with EoE.

Conclusions: Despite the lack of an agreed set of core outcomes that should be recorded and reported in studies in adult EoE patients, endoscopic EoE-associated findings and esophageal eosinophil density are commonly used to assess disease activity in observational studies. Standardization of outcomes and data supporting the use of outcomes are needed to facilitate interpretation of evidence, its synthesis, and comparisons of interventions in meta-analyses of therapeutic trials in adults with EoE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000516898DOI Listing
September 2021

Effects of anti-TNF therapy and immunomodulators on anxiety and depressive symptoms in patients with inflammatory bowel disease: a 5-year analysis.

Therap Adv Gastroenterol 2021 31;14:17562848211033763. Epub 2021 Aug 31.

Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, Switzerland.

Background And Aims: Anxiety and depression are prevalent in patients with inflammatory bowel diseases (IBD), especially during IBD flares. IBD therapies can profoundly affect the mood of patients with IBD. We aimed to determine the long-term impact of anti-tumor necrosis factor (anti-TNF) and immunomodulators (IM) on anxiety and depressive symptoms in IBD patients.

Methods: We compared three treatment groups with IM only (group A), anti-TNF ± IM (group B) and no such therapy (group C). Patients completed the hospital anxiety and depression scale (HADS) at 1 year, 3 years, and 5 years after start of treatment.

Results: In total, 581 patients with IBD (42.9% Crohn's disease, 57.1% ulcerative colitis/IBD unclassified) participated in this study. Effects of treatment were analyzed in a mixed effects model, with and without correction for confounders. Compared with group C, group B showed a significant treatment-related improvement in both anxiety and depressive symptoms within the first 2.5 years and also thereafter. Group A showed a significant long-term improvement of anxiety and both short-term and long-term improvement in depressive symptoms. The significance of these results was maintained after correction for confounders, including corticosteroid treatment. Additionally, both groups A and B showed a significant decrease in disease activity in the first 2.5 years after start of treatment and also thereafter. Anti-TNF and IM treatment were associated with a similarly significant decrease in anxiety and depressive symptoms over an observation period of up to 5 years.

Conclusion: Besides a clear benefit for disease activity, anti-TNF and IM apparently improve the mood of patients with IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/17562848211033763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411653PMC
August 2021

The impact of colectomy on the course of extraintestinal manifestations in Swiss inflammatory bowel disease cohort study patients.

United European Gastroenterol J 2021 Aug 25. Epub 2021 Aug 25.

Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Zurich, Switzerland.

Background And Aims: Extraintestinal manifestations are reported to occur in up to 45% of inflammatory bowel disease (IBD) patients during the course of disease. It is unknown whether colectomy reduces the rate of de novo extraintestinal manifestations (EIMs) or impacts on severity of EIMs following a parallel versus independent disease course from underlying IBD.

Methods: Using data from the Swiss Inflammatory Bowel Disease Cohort Study we aimed to analyse the course of EIMs in ulcerative colitis (UC) and Crohn's disease (CD) patients undergoing colectomy during the cohort's prospective follow-up.

Results: One hundred and twenty-one IBD patients (33 CD, 81 UC and seven unclassified) underwent colectomy during prospective follow-up in the Swiss Inflammatory Bowel Disease Cohort Study. Within the 114 patients with UC or CD any EIM was reported in 40 (nine CD and 31 UC) patients. Activity of EIMs ceased entirely after colectomy in 21 patients (52.5%). Complete cessation of EIM after colectomy was higher in patients with UC versus CD with 58.1% versus 33.3%. After colectomy, 29 out of the 114 patients (25.4%) experienced any EIM. Two thirds of these (19 patients) represented persisting EIMs, while in one third (10 patients) EIM represented a de-novo event after colectomy. Overall, 13.5% of IBD patients developed a de-novo EIM after colectomy.

Conclusions: In IBD patients undergoing colectomy, EIMs present prior to surgery will persist in about half of patients. Complete cessation of EIM after colectomy may be less common in CD than in UC. In patients who never experienced EIMs prior to colectomy de-novo manifestations thereafter should be expected in up to one in seven patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ueg2.12125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435245PMC
August 2021

Is There a Role for Topical Swallowed Steroids upon Emergency Room Admission for Suspected Food Bolus Obstruction in Eosinophilic Esophagitis?

Dysphagia 2021 Aug 16. Epub 2021 Aug 16.

Department of Gastroenterology and Hepatology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.

Since most pharmacological treatments in case of esophageal food impaction (EFI) are unsuccessful, an endoscopy is usually required to resolve EFI. We present the first results of a budesonide orodispersible tablet (BOT) as a medical treatment option before endoscopy. We evaluated all patients with a suspected EFI to receive BOT before emergent endoscopy at a tertiary hospital between March 2019 and June 2020. A total of eight patients received BOT before endoscopy. Mean age was 50.1 years and 87.5% were male. In 38% (3/8) of patients the EFI resolved without endoscopic intervention. No adverse events occurred. After endoscopy, a diagnosis of EoE was established in 75%. This case series demonstrate the potential of BOT as medical rescue therapy in case of EFI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00455-021-10354-9DOI Listing
August 2021

Genotype-phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients.

BMC Gastroenterol 2021 Aug 3;21(1):310. Epub 2021 Aug 3.

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

Background: Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn's Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS).

Methods: We included 981 Crohn's disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients.

Results: In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays.

Conclusions: In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-021-01880-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336111PMC
August 2021

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

J Allergy Clin Immunol 2021 Jul 6. Epub 2021 Jul 6.

Inform Diagnostics, Irving, Tex; Department of Pathology, Baylor College of Medicine, Houston, Tex.

Background: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments.

Objective: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE.

Methods: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists.

Results: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life.

Conclusions: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.07.001DOI Listing
July 2021

A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease.

N Engl J Med 2021 07;385(1):35-45

From the Institute of Translational Immunology and Celiac Center, Research Center for Immune Therapy, University Medical Center, Johannes Gutenberg University, Mainz (D.S., T.F.-S.), the Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg (J.L.), the Department of Integrative Medicine, University of Duisburg-Essen, Duisburg-Essen (J.L.), the Division of Gastroenterology, Hepatology, and Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, Tübingen (S.F.), the Department of Gastroenterology, Infectious Diseases, and Rheumatology, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin (M. Schumann), the Department of Medicine II, University Hospital, Ludwig Maximilians University, Munich (H.P.T.), the Department of Medicine 1, Hector Center for Nutrition, Exercise, and Sports, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen (Y.Z.), the Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg (A.W.L.), the Department of Internal Medicine IV, University Hospital, Friedrich-Schiller University Jena, Jena (A.S.), and Dr. Falk Pharma, Freiburg (R.M., R.G.) - all in Germany; the Division of Gastroenterology and Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (D.S.); the Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital (M.M., A.P., M.-L.L.), the Faculty of Medicine and Health Technology, Tampere University (J.I., J.T.), Jilab (J.I.), and the Department of Pediatrics, Tampere University Hospital (M.-L.L.), Tampere, the Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä (J.T.), Lääkärikeskus Aava Helsinki Kamppi, Helsinki (J. Koskenpato), and Clinical Research Services Turku, Turku (M. Scheinin) - all in Finland; Oslo University Hospital, Rikshospitalet, and Stiftelsen K.G. Jebsen Celiac Disease Research Center, University of Oslo, Oslo (K.E.A.L.), the Medical Department, Innlandet Hospital Trust, Gjøvik (O.H.), and Akershus University Hospital, Lørenskog (J.J.) - all in Norway; the University of Medicine and Pharmacy "Carol Davila" and the National Institute for Mother and Child Health "Alessandrescu-Rusescu," Bucharest, Romania (A.P.); the Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania (J. Kupcinskas); the Department of Gastroenterology, Internal Medicine Clinic, Tartu University Hospital, Tartu, Estonia (K.K.); the Department of Gastroenterology and Hepatology, University Hospital Zurich (L.B., J.Z.), and the Swiss Celiac Center, Center of Gastroenterology, Clinic Hirslanden (J.Z.) - both in Zurich, Switzerland; and University College Hospital Galway, Galway, Ireland (V.B.).

Background: In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease.

Methods: In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point was the attenuation of gluten-induced mucosal damage, as measured by the ratio of villus height to crypt depth. Secondary end points included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score (for assessment of health-related quality of life).

Results: Of the 41 patients assigned to the 10-mg ZED1227 group, the 41 assigned to the 50-mg group, the 41 assigned to the 100-mg group, and the 40 assigned to the placebo group, 35, 39, 38, and 30 patients, respectively, had adequate duodenal-biopsy samples for the assessment of the primary end point. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 0.44 (95% confidence interval [CI], 0.15 to 0.73) in the 10-mg group (P = 0.001), 0.49 (95% CI, 0.20 to 0.77) in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001). The estimated differences from placebo in the change in intraepithelial lymphocyte density were -2.7 cells per 100 epithelial cells (95% CI, -7.6 to 2.2) in the 10-mg group, -4.2 cells per 100 epithelial cells (95% CI, -8.9 to 0.6) in the 50-mg group, and -9.6 cells per 100 epithelial cells (95% CI, -14.4 to -4.8) in the 100-mg group. Use of the 100-mg dose may have improved symptom and quality-of-life scores. The most common adverse events, the incidences of which were similar across all groups, were headache, nausea, diarrhea, vomiting, and abdominal pain. Rash developed in 3 of 40 patients (8%) in the 100-mg group.

Conclusions: In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease. (Funded by Dr. Falk Pharma; CEC-3 EudraCT number, 2017-002241-30.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2032441DOI Listing
July 2021

Eosinophilic esophagitis-established facts and new horizons.

Semin Immunopathol 2021 06 7;43(3):319-335. Epub 2021 Jun 7.

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

Despite dramatic advances in our understanding of the pathogenesis and course of disease in the relatively short timeframe since the discovery and first description of eosinophilic esophagitis (EoE) less than three decades ago, many open questions remain to be elucidated. For instance, we will need to better characterize atypical clinical presentations of EoE and other forms of esophageal inflammatory conditions with often similar clinical presentations, nut fulfilling current diagnostic criteria for EoE and to determine their significance and interrelationship with genuine EoE. In addition, the interrelationship of EoE with other immune-mediated diseases remains to be clarified. Hopefully, a closer look at the role of environmental factors and their interaction with genetic susceptibility often in context of atopic predisposition may enable identifying the candidate substances/agents/allergens and potentially earlier (childhood) events to trigger the condition. It appears plausible to assume that in the end-comparable to current concepts in other immune-mediated chronic diseases, such as for instance inflammatory bowel disease or asthma bronchiale-we will not be rewarded with the identification of a "one-and-only" underlying pathogenetic trigger factor, with causal responsibility for the disease in each and every EoE patient. Rather, the relative contribution and importance of intrinsic susceptibility, i.e., patient-driven factors (genetics, aberrant immune response) and external trigger factors, such as food (or aero-) allergens as well as early childhood events (e.g., infection and exposure to antibiotics and other drugs) may substantially differ among given individuals with EoE. Accordingly, selection and treatment duration of medical therapy, success rates and extent of required restriction in dietary treatment, and the need for mechanical treatment to address strictures and stenosis require an individualized approach, tailored to each patient. With the advances of emerging treatment options, the importance of such an individualized and patient-centered assessment will increase even further.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00281-021-00855-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241662PMC
June 2021

Depressive Symptoms Predict Clinical Recurrence of Inflammatory Bowel Disease.

Inflamm Bowel Dis 2021 Jun 7. Epub 2021 Jun 7.

Neurology, Department of Biomedical Research, Bern University Hospital, University of Bern, Bern, Switzerland.

Background: Inflammatory bowel disease (IBD) patients are at high risk for depression, and depression has been shown to affect disease course. We examined interrelations between depression, genetic risk factors for depression, and IBD flares.

Method: In 1973 patients (1137 Crohn's disease, 836 ulcerative colitis) of the Swiss IBD Cohort Study (SIBDCS), depressive status (hospital anxiety and depression subscale for depression, HADS-D ≥11) was assessed on a yearly basis. We investigated the impact of depression on IBD-relevant clinical outcomes in Cox proportional hazards models. We used active disease (CDAI ≥150 or MTWAI ≥10) and 2 published composite flare definitions-FNCE (physician-reported flare, nonresponse to therapy, new complication, or extraintestinal manifestation) and AFFSST (active disease, physician-reported flare, fistula, stenosis, and new systemic therapy)-as clinical end points. Additionally, 62 preselected single nucleotide polymorphisms (SNPs) were screened for cross-sectional associations with depression, and if present, their predictive value for future depression and clinical deterioration was assessed.

Results: Depression was a strong risk factor for disease-related end points, including active disease (adjusted hazard ratio [aHR], 3.55; P < 0.001), AFFSST (aHR, 1.62; P < 0.001), and FNCE (aHR, 1.35; P = 0.019). The SNP rs2522833 was significantly associated with depression at enrollment (q = 0.059). The TC allele of rs588765 was negatively associated with the presence of depression at enrollment (q = 0.050) and after enrollment (aHR, 0.67; P = 0.035) and with fewer active disease states (aHR, 0.72; P = 0.045) during follow-up.

Conclusion: In IBD, depressive symptoms and inflammatory activity are intimately related. Depressive symptoms were a strong predictor of clinical deterioration, and genetic markers may play a role in this relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ibd/izab136DOI Listing
June 2021

Technical feasibility, clinical effectiveness, and safety of esophageal stricture dilation using a novel endoscopic attachment cap in adults with eosinophilic esophagitis.

Gastrointest Endosc 2021 May 15. Epub 2021 May 15.

Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.

Background And Aims: The BougieCap (Ovesco Endoscopy AG, Tübingen, Germany) is a new device that allows optical and tactile feedback during stricture dilation of the upper GI tract. We evaluated the technical feasibility, clinical efficacy, and safety of a 1-time esophageal stricture dilation using the BougieCap in adults with eosinophilic esophagitis (EoE).

Methods: EoE patients prospectively included in the Swiss EoE Cohort were dilated with the BougieCap for esophageal strictures (esophageal diameter, ≤14 mm) and stricture-related symptoms. Symptoms were assessed before and 2 weeks after a single dilation session using the validated Eosinophilic Esophagitis Activity Index Patient Reported Outcomes instrument (score ranges from 0 to 100 points).

Results: Fifty patients (70% men; median age, 41 years; median disease duration, 4 years; 50% treated with swallowed topical corticosteroids, 10% with proton pump inhibitors, 14% with combined swallowed topical corticosteroids plus proton pump inhibitors, 14% with elimination diet, 12% without antieosinophil therapy) were evaluated. Endoscopic bougienage was technically successful in 100%. The median esophageal diameter increased from 12 mm (interquartile range [IQR], 12-13) to 16 mm (IQR, 16-16; P < .001). Median symptom severity dropped from 32 points (IQR, 27-41) to 0 (IQR, 0-10; P < .001) at 2 weeks postdilation. In 1 patient the BougieCap was temporarily lost after stricture dilation in the hypopharynx but could be retrieved. No severe adverse events were reported.

Conclusions: In adults with EoE, endoscopic treatment of esophageal strictures using the BougieCap is technically feasible and safe and offers significant symptomatic improvement in the short term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2021.05.017DOI Listing
May 2021

Type D personality is associated with depressive symptoms and clinical activity in inflammatory bowel disease.

Aliment Pharmacol Ther 2021 07 11;54(1):53-67. Epub 2021 May 11.

Clinic for Visceral Surgery and Medicine, Inselspital Bern and Bern University, Bern, Switzerland.

Background: Inflammatory bowel disease (IBD) can be exacerbated by stress and depression. Type D personality, characterised by high negative affectivity and social inhibition, represents a vulnerability towards stressors and is associated with adverse outcomes in coronary heart disease.

Aims: To assess the prevalence of Type D personality in IBD patients and investigate potential associations with disease course.

Methods: We tested for associations between Type D (Type D Scale-14), depressive symptoms (Hospital Anxiety and Depression Scale's depression subscore ≥11) and recurrent IBD amongst Swiss IBD cohort patients. We built regression models for cross-sectional and Cox proportional hazards models for time-to-event analyses. IBD disease course was assessed by the future occurrence of active disease (Crohn's Disease Activity Index ≥150/Modified Truelove & Witts activity index ≥10) and several IBD-relevant endpoints.

Results: Amongst 2275 patients (1005 ulcerative colitis, 1270 Crohn's disease), 672 (29.5%) had Type D. Type D was a significant risk factor for future active disease (adjusted hazard ratio, aHR: 1.60, corrected P value, q = 0.007) and predicted the future presence of depressive symptoms (aHR: 3.30, P < 0.001). The combination of Type D and depressive symptoms further increased the risk for active disease (aHR: 3.98, q < 0.001). However, Type D associated depressive symptoms seemed to be the main contributor to this effect as Type D's predictive power decreased considerably in models corrected for depressive symptoms (aHR: 1.32, CI: 0.97-1.79, q = 0.292).

Conclusions: Type D personality's prevalence amongst IBD patients was comparable with its prevalence in the general population. Type D was strongly associated with depressive symptoms and showed modest independent associations with IBD prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16365DOI Listing
July 2021

Long-term immune-related adverse events after discontinuation of immunotherapy.

Immunotherapy 2021 Jun 22;13(9):735-740. Epub 2021 Apr 22.

Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland.

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and ipilimumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt-2020-0320DOI Listing
June 2021

Clinical Relevance of Anti-TNF Antibody Trough Levels and Anti-Drug Antibodies in Treating Inflammatory Bowel Disease Patients.

Inflamm Intest Dis 2021 Feb 20;6(1):38-47. Epub 2020 Nov 20.

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

Background And Aims: The majority of patients treated with anti-tumor necrosis factor (TNF) therapy develop anti-drug antibodies (ADAs), which might result in loss of treatment efficacy. Strict guidelines on measuring trough levels (TLs) and ADA in clinical routine do not exist. To provide real-world data, we took advantage of our tertiary inflammatory bowel disease (IBD) center patient cohort and determined indicators for therapeutic drug monitoring (TDM) and actual consequences in patient care.

Methods: We retrospectively collected clinical data of 104 IBD patients treated with infliximab or adalimumab in our IBD clinic. Patients with TL and ADA measurements between June 2015 and February 2018 were included.

Results: The main reason for determining TL was increased clinical disease. Subtherapeutic TLs were found in 33 patients, therapeutic TLs in 33 patients, and supratherapeutic TLs in 38 patients. Adjustments in anti-TNF therapy occurred more frequently ( = 0.01) in patients with subtherapeutic TL (24 of 33 patients; 73%) as compared to patients with therapeutic and supratherapeutic TLs (26 of 71 patients; 37%). No correlation could be found between TL and disease activity ( = 0.16). Presence of ADA was found in 16 patients, correlated with the development of infusion reactions (OR: 10.6, RR: 5.4, CI: 2.9-38.6), and was associated with subtherapeutic TL in 15 patients (93.8%). Treatment adaptations were based on TL and/or ADA presence in 36 of 63 patients.

Conclusions: TDM showed significant treatment adaptations in patients with subtherapeutic TL. Conversely, in patients with therapeutic and supratherapeutic TLs, reasons for adaptations were based on considerations other than TL, such as clinical disease activity. Further studies should focus on decision-making in patients presenting with supratherapeutic TL in remission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000511296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015259PMC
February 2021

Defer No Time, Delays Have Dangerous Ends (William Shakespeare).

Gastroenterology 2021 Jul 1;161(1):42-44. Epub 2021 Apr 1.

Department of Gastroenterology and Hepatology, Clarunis, Basel, Switzerland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.03.055DOI Listing
July 2021

Perianal fistulodesis - A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae.

World J Gastrointest Surg 2021 Feb;13(2):187-197

Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland.

Background: Perianal fistulae strongly impact on quality of life of affected patients.

Aim: To challenge and novel minimally invasive treatment options are needed.

Methods: Patients with Crohn's disease (CD) in remission and patients without inflammatory bowel disease (non-IBD patients) were treated with fistulodesis, a method including curettage of fistula tract, flushing with acetylcysteine and doxycycline, Z-suture of the inner fistula opening, fibrin glue instillation, and Z-suture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks. Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included. The primary end point was fistula healing, defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk.

Results: Fistulodesis was performed in 17 non-IBD and 3 CD patients, with a total of 22 fistulae. After 24 wk, all fistulae were healed in 4 non-IBD and 2 CD patients (overall 30%) and fistula remained closed until the end of follow-up at 10-25 mo. In a secondary per-fistula analysis, 7 out of 22 fistulae (32%) were closed. Perianal disease activity index (PDAI) improved in patients with fistula healing. Low PDAI was associated with favorable outcome ( = 0.0013). No serious adverse events were observed.

Conclusion: Fistulodesis is feasible and safe for perianal fistula closure. Overall success rates is at 30% comparable to other similar techniques. A trend for better outcomes in patients with low PDAI needs to be confirmed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4240/wjgs.v13.i2.187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898183PMC
February 2021

Higher educational level in patients with eosinophilic esophagitis: a comparative analysis.

Dis Esophagus 2021 Sep;34(9)

Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Zurich, Switzerland.

Background: Eosinophilic esophagitis is a chronic inflammatory gastrointestinal disease with a high prevalence in younger, atopic males. In our clinical practice, we observed a striking preponderance of patients having a high educational background. The purposes of this study were first to assess the level of education of eosinophilic esophagitis patients and second to compare the findings to patients with inflammatory bowel disease, another chronic immune-mediated condition of the gastrointestinal tract, and with the Swiss general population.

Methods: Using a questionnaire, we assessed the educational level of adult patients who have attended Swiss Eosinophilic Esophagitis Clinics in the past. In addition, the educational level of the parents was assessed as well. We calculated the proportions of patients and parents who have obtained a higher educational level. Data from the Swiss Inflammatory Bowel Disease Cohort Study and from the Swiss general population served as confirmation and as comparison, respectively.

Results: A total of 277 successfully contacted patients (response rate 69.1%; mean age 51.1 years, 73% male) participated. A significantly higher proportion of surveyed eosinophilic esophagitis patients had a high International Standard Classification of Education level (66.8%, P < 0.001) compared with inflammatory bowel disease patients (n = 2534; 34.2%, P < 0.001) and to the Swiss general population (n = 6,066,907; 30.5% P < 0.001).

Conclusion: Our analysis confirms the clinical observation that eosinophilic esophagitis patients have a significantly higher educational level compared with the general population and to patients with other chronic inflammatory diseases of the gastrointestinal tract. As a limitation, this impressive finding remains on a purely descriptive level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/dote/doab010DOI Listing
September 2021

Allogeneic expanded adipose-derived mesenchymal stem cell therapy for perianal fistulas in Crohn's disease: A case series.

Colorectal Dis 2021 06 5;23(6):1444-1450. Epub 2021 Mar 5.

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

Aim: Even with optimal medical and surgical therapy, perianal fistulas in patients with Crohn's disease (CD) have low closure rates. As a new therapeutic option, administration of local mesenchymal stem cells (MSCs) has proved to be an innovative option after failure of treatment with immunosuppressive or immunomodulatory agents. The aim of this work is to share our first experience with MSC administration and demonstrate its efficacy, safety and feasibility outside a clinical trial.

Method: A total of 11 CD patients with complex perianal fistulas with nonactive or mildly active luminal disease were treated with local injection of 120 million allogeneic adipose-derived stem cells at a tertiary hospital between February 2019 and June 2020.

Results: The mean age of the 11 patients was 38.3 years, 72.7% were men and 27.2% were smokers. The mean duration of fistula manifestation was 7.8 years and, except for one patient (therapy with tacrolimus), all other patients had been treated with an antitumour necrosis factor agent without fistula healing in the last 6 months. After a mean follow-up time of 41.5 weeks, 72.7% (8/11) of patients had complete closure of their fistula and three patients failed MSC treatment. Complete fistula healing could be observed 4-6 weeks postoperatively in half of the patients, while 36.5% (4/11) of patients developed a perianal abscess which had to be drained. One patient experienced cytomegalovirus viraemia 2 weeks after MSC administration and one patient developed a testicular carcinoma 16 weeks after treatment.

Conclusion: This case series demonstrates that the efficacy and safety of darvadstrocel in the ADMIRE trial can be replicated outside a clinical trial. This new modality in the treatment of complex perianal fistulas appears to be a promising therapeutic option for a challenging patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/codi.15587DOI Listing
June 2021

Abdominal pain in patients with inflammatory bowel disease: association with single-nucleotide polymorphisms prevalent in irritable bowel syndrome and clinical management.

BMC Gastroenterol 2021 Feb 5;21(1):53. Epub 2021 Feb 5.

Department of Gastroenterology, University Hospital Zurich (USZ), Zurich University, Zurich, Switzerland.

Background: Abdominal pain is a frequent symptom in patients with inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC). Pain can result from ongoing inflammation or functional disorders imitating irritable bowel syndrome (IBS). Several single-nucleotide polymorphisms (SNPs) have been associated with IBS. However, the impact of IBS genetics on the clinical course of IBD, especially pain levels of patients remains unclear.

Methods: Data of 857 UC and 1206 CD patients from the Swiss IBD Cohort Study were analysed. We tested the association of the maximum of the abdominal pain item of disease activity indices in UC and CD over the study period with 16 IBS-associated SNPs, using multivariate ANOVA models.

Results: In UC patients, the SNPs rs1042713 (located on the ADRB2 gene) and rs4663866 (close to the HES6 gene) were associated with higher abdominal pain levels (P = 0.044; P = 0.037, respectively). Abdominal pain was not associated with any markers of patient management in a model adjusted for confounders. In CD patients, higher levels of abdominal pain correlated with the number of physician contacts (P < 10), examinations (P < 10), medical therapies (P = 0.023) and weeks of hospitalisation (P = 0.0013) in a multivariate model.

Conclusions: We detected an association between maximal abdominal pain in UC patients and two IBS-associated SNPs. Abdominal pain levels had a pronounced impact on diagnostic and therapeutic procedures in CD but not in UC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-021-01622-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866750PMC
February 2021

Diet and Inflammatory Bowel Disease: What Quality Standards Should Be Applied in Clinical and Laboratory Studies?

Mol Nutr Food Res 2021 03 22;65(5):e2000514. Epub 2021 Feb 22.

Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, 27599-7080, USA.

Many patients suffering from inflammatory bowel disease (IBD) follow restrictive diets, as many respective recommendations circulate. Efforts are made to evaluate and summarize the published information, for example, in a recent consensus manuscript by the International Organization for the Study of IBD (IOIBD). However, the standards that should be applied to make claims about dietary effects are poorly defined. In this manuscript, the scientific basis of recommendations for nutritional interventions in IBD is analyzed. Epidemiological evidence on diet in IBD is always biased by numerous factors, and the number of robust dietary intervention studies is limited due to methodological difficulties. Therefore, animal models are used to test hypotheses with respect to dietary factors and intestinal inflammation. Naturally, animal models have limitations, and knowledge of key characteristics of colitis animal models is crucial to understand their advantages and disadvantages. In recent years the important role of the microbiota for IBD and dietary factors has been discovered. Microbiota data are added to many publications on IBD and nutrition. The quality of those data varies largely. Subsequently, quality standards for microbiota analyses also are discussed. Finally, quality requirements to be applied on recommendations for dietary changes in patients with IBD are suggested.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mnfr.202000514DOI Listing
March 2021

Protein-losing enteropathy as precursor of inflammatory bowel disease: a review of the literature.

BMJ Case Rep 2021 Jan 11;14(1). Epub 2021 Jan 11.

Department for Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

We report the case of a 63-year-old female patient with liver cirrhosis who presented with symptoms of severe hypoalbuminaemia and diarrhoea. After ruling out other causes of hypoalbuminaemia and confirmation of an elevated faecal α-1 antitrypsin clearance, the diagnosis of protein-losing enteropathy (PLE) could be established. Since PLE is a syndrome caused by various diseases, classified into erosive and non-erosive gastrointestinal diseases or lymphatic obstruction, an extensive work-up was necessary, establishing the final diagnosis of Crohn's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2020-238802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802676PMC
January 2021

The Influence of Breastfeeding, Cesarean Section, Pet Animals, and Urbanization on the Development of Inflammatory Bowel Disease: Data from the Swiss IBD Cohort Study.

Inflamm Intest Dis 2020 Nov 26;5(4):170-179. Epub 2020 Aug 26.

Clinic for Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Introduction: The pathophysiology of inflammatory bowel disease (IBD) is incompletely understood. Current concepts imply that environmental factors (EFs) trigger disease onset as well as flares in genetically susceptible individuals.

Objective: The objective of this study is to analyze the association between IBD and various EFs, which may influence the pathogenesis of the disease.

Methods: 2,294 patients from the Swiss IBD Cohort Study (SIBDCS) received a questionnaire regarding EF including mode of delivery, breastfeeding, animals in household, and place of residence. The control group comprised patients' childhood friends, who grew up in a similar environment ("friends cohort").

Results: A total of 1,111 questionnaires were returned from SIBDCS patients (response rate: 48.4%). Breastfeeding for <6 months was associated with a decreased risk for ulcerative colitis/indeterminate colitis (UC/IC) (OR: 0.473, = 0.006). IBD patients reported less pet animals in the household than the control group ( = 0.004). The presence of cats or dogs (OR: 0.688, = 0.015) and pet rodents (OR: 0.598, = 0.001) in the household before the age of 20 was inversely associated with the risk for UC/IC.

Conclusion: The present study underlines the importance of EFs in the pathogenesis of IBD. Overall, the development of UC/IC seems to be more affected from environmental influences than from Crohn's disease. Our results imply a protective effect of possessing pet animals in household and short breastfeeding regarding the onset of UC/IC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706488PMC
November 2020

Genetic risk factors predict disease progression in Crohn's disease patients of the Swiss inflammatory bowel disease cohort.

Therap Adv Gastroenterol 2020 19;13:1756284820959252. Epub 2020 Nov 19.

Department of Gastroenterology and Hepatology, University Hospital Zurich, Rämistrasse 100, Zurich, 8091, Switzerland.

Background: Crohn's disease (CD) may progress from an inflammatory to a stricturing or penetrating disease phenotype. The aim of our study was to identify single nucleotide polymorphisms (SNPs) that predict disease progression in patients of the Swiss IBD Cohort Study (SIBDCS).

Methods: We applied a multi-state Markov model for progression behavior of CD with three behavioral states according to the Montreal classification. The model considered transition from B1 to B2/B3 or from B2 to B3 stage. Model dynamics were summarized with transition intensities by including the effect of SNPs and calculating transition intensities for each SNP.

Results: We included 1276 CD patients [669 (52.4%) B1, 248 (19.4%) B2, 359 (28.1%) B3 patients] with a median follow-up of 6.8 (interquartile range = 3.6-9.1; range 0-11.6) years. Probability for a B1 patient to develop a stenosis (B1 to B2, q = 0.033) was twice as much as compared to developing a penetrating complication (B3) during the disease course. In contrast, the probability of entering B3 stage was similar regardless of whether antecedent stricture was present (B2 to B3, q = 0.016) or not (B1 to B3, q = 0.016). We identified SNPs within the gene loci encoding ZMIZ1, LOC105373831 and KSR1 as carrying the highest risk for progression to B3, while the presence of SNPs within gene loci TNFSF15 and CEBPB-PTPN1 protected from progression to B2 or B3.

Conclusion: We identified new genetic risk factors that can predict disease course in CD patients. A closer understanding on the functional impact of these genetic variations might improve our treatment options finally to prevent disease progression in CD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1756284820959252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686597PMC
November 2020

Impact of obesity on disease activity and disease outcome in inflammatory bowel disease: Results from the Swiss inflammatory bowel disease cohort.

United European Gastroenterol J 2020 12;8(10):1196-1207

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

Objective: The purpose of this study was to investigate the impact of obesity on disease activity and disease outcome in patients with inflammatory bowel disease.

Patients And Methods: The impact of obesity on inflammatory bowel disease disease activity and outcome was retrospectively assessed in 3075 patients enrolled in the prospective nation-wide Swiss inflammatory bowel disease cohort between July 2006 and September 2018. Baseline characteristics, disease activity and disease course in 325 obese inflammatory bowel disease patients (body mass index ≥30 kg/m) were compared to 1725 normal weight inflammatory bowel disease individuals (body mass index 18.5-24.9).

Results: Among 3075 patients in the prospective Swiss inflammatory bowel disease cohort, 325 patients (10.6%) were obese, namely, 194 Crohn's disease patients, 131 ulcerative colitis, and inflammatory bowel disease-unclassified patients. Disease activity scores were elevated in obese Crohn's disease (Crohn's Disease Activity Index 33 vs 20,  = 0.001), but not ulcerative colitis patients. Obese Crohn's disease, but not ulcerative colitis patients were less likely to be in remission based on a Crohn's Disease Activity Index less than 100 and a calprotectin less than 100 ug/g. In a multivariate regression model, obesity was negatively associated with disease remission in Crohn's disease (odds ratio 0.610, 95% confidence interval 0.402-0.926,  = 0.020), but not ulcerative colitis. Increased soft stool frequency was observed in both obese Crohn's disease and ulcerative colitis patients. Adjusted Cox regression models revealed increased risk of complicated disease course in obese Crohn's disease patients (hazard ratio 1.197, 95% confidence interval 1.046-1.370,  = 0.009). No association between obesity and disease progression, index treatment failure was seen neither in Crohn's disease nor ulcerative colitis.

Conclusion: Obesity is associated with decreased rates of disease remission and increased risk of complicated disease course in Crohn's disease over a six-year follow-up period. No effects were seen on disease progression and index treatment failure neither in Crohn's disease nor ulcerative colitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2050640620954556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724522PMC
December 2020

Factors influencing the outcome of vedolizumab treatment: Real-life data with objective outcome measurements.

United European Gastroenterol J 2021 Apr 26;9(3):398-406. Epub 2021 Feb 26.

Crohn-Colitis Centre, Bern, Switzerland.

Background: Vedolizumab (VDZ), a humanised monoclonal antibody against a4ß7-integrin, has shown efficacy in inflammatory bowel disease (IBD). It is of importance to assess the mid-to long-term efficacy of VDZ using real-life data.

Objective: Our study aimed to determine the efficacy of VDZ in patients with IBD with and without prior exposure to anti-tumour necrosis factor (TNF) treatments in a real-life setting. Furthermore, we investigated confounding factors influencing the remission to VDZ.

Methods: Patients participating in the Swiss IBD Cohort Study were included in this study. Remission was defined as calprotectin less than 200 mg/kg stool and/or mucosal healing determined by endoscopy. End points were determined between Months 4 and 8 (T1) and between Months 12 and 16 (T2) after VDZ induction.

Results: Remission was reported in 50.5% (110/218) of patients in T1 (48.7% Crohn's disease [CD] and 52.5% ulcerative colitis [UC]) and 46.8% (102/218) in T2 (47% CD and 46.5% UC). In UC patients, a significantly higher remission rate was achieved in T2 among anti-TNF-naive patients (57.7%) compared to anti-TNF-experienced patients (34.7%; p = 0.02; odds ratio = 0.39, 95% confidence interval: 0.17-0.87). In patients with CD, no difference could be seen in either evaluation interval. Multivariable analysis showed that disease duration significantly influenced remission rates among UC patients. A late response to VDZ therapy with an achievement of remission in T2 was seen in a fifth of all patients (CD: 21.7%, UC: 20.8%). VDZ treatment was stopped in a third of all patients (31.8%) due to nonresponse, adverse events or aggravation of extra-intestinal manifestations.

Conclusion: In a real-life national cohort setting, VDZ induced remission in more than half of IBD patients. Previous treatment with anti-TNF agents was associated with a significant lower efficacy of VDZ in UC but not in CD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2050640620965106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259282PMC
April 2021

Fatigue in inflammatory bowel disease and its impact on daily activities.

Aliment Pharmacol Ther 2021 01 7;53(1):138-149. Epub 2020 Nov 7.

Department of Gastroenterology & Hepatology, University Hospital Zurich, Zurich, Switzerland.

Background: Fatigue is a common symptom of chronic inflammation, including inflammatory bowel disease (IBD), resulting in significant impairment in quality of life.

Aims: To identify the prevalence of fatigue in a large IBD cohort compared to the general population, address risk factors, and evaluate its impact on daily life.

Methods: We evaluated 1208 IBD patients from the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS) and 414 healthy controls. Significant fatigue was defined as a visual analogue scale (VAS-F, range 0-10) score ≥ 4. Secondary endpoints were severity of fatigue and its impact on daily activities with the Fatigue Severity Scale (FSS), with a score ≥ 4 indicative of fatigue. Demographic, IBD-related and psychiatric symptoms were assessed with a multivariate analysis of variance (MANOVA) model optimised for prediction of VAS-F (primary outcome) and FSS scores.

Results: Overall, 672 IBD patients (55.6%) reported significant fatigue compared to 145 (35%) controls (OR 2.71; 95% CI 2.08-3.54; P < 0.001). In IBD, fatigue also significantly affected daily activities (FSS ≥ 4; 405 (33.5%) IBD patients vs 81 (19.6%) controls, P < 0.001). In the MANOVA model, fatigue levels were associated with female gender (coefficient 0.839; 0.556 - 1.123; P < 0.001), younger age at diagnosis (-0.031 per year; -0.042- -0.019; P < 0.001), shorter disease duration (-0.036 per year; -0.050- -0.022; P < 0.001), nocturnal diarrhoea (0.718; 0.295-1.141; P = 0.001), low educational level (P = 0.034) and symptoms of depression and anxiety.

Conclusions: Fatigue is both more frequent and more severe in patients with IBD than in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16145DOI Listing
January 2021

How to approach adult patients with asymptomatic esophageal eosinophilia.

Dis Esophagus 2021 Jan;34(1)

Department of Gastroenterology & Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

As the awareness among gastroenterologists regarding endoscopic features suggesting eosinophilic esophagitis is increasing, individuals without symptoms of esophageal dysfunction are increasingly being found to have esophageal eosinophilia on biopsies performed during upper gastrointestinal endoscopies. However, the course of disease and the management of these asymptomatic individuals with esophageal eosinophilia remain elusive. In this review, we propose a definition of asymptomatic individuals with esophageal eosinophilia and discuss the prevalence, risk factors, and course of disease of this specific patient group. Furthermore, we have established a diagnostic and therapeutic pathway based on the most recent available data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/dote/doaa105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947174PMC
January 2021

Retrospective Analysis of Treatment and Complications of Immune Checkpoint Inhibitor-Associated Colitis: Histological Ulcerations as Potential Predictor for a Steroid-Refractory Disease Course.

Inflamm Intest Dis 2020 Aug 26;5(3):109-116. Epub 2020 May 26.

Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background/aims: Among the severe immune-related adverse events (irAEs) that occur with immune checkpoint inhibitor (ICI) therapy, colitis is the most frequent one. This study aimed at describing the experience from the largest gastroenterology unit in Switzerland with immune checkpoint inhibitor-associated colitis (ICIAC), its clinical presentation, management, and outcomes.

Methods: We performed a retrospective review of patients who were referred for the evaluation of ICIAC between January 2011 and October 2018 to the Division of Gastroenterology and Hepatology, University Hospital Zurich.

Results: Thirty-three patients with immune-related colitis grade 3 or 4 met the inclusion criteria and were analyzed in detail: All patients had diarrhea, 64% had abdominal pain, 42% had bloody stool, 27% had emesis, and 18% developed fever. In total, 33% were successfully treated with corticosteroids alone; 66% were steroid-refractory and treated with infliximab or vedolizumab. Two of these patients developed severe complications requiring surgery. All patients reached complete remission of ICIAC and its symptoms. At colonoscopy, ulcerations were seen in 37% of steroid-refractory versus 63% of steroid-responsive cases. Deep histological ulcerations invading the submucosa were only present in steroid-refractory cases.

Conclusion: ICIAC is a severe irAE which frequently requires high-dose steroids and a close follow-up due to deleterious complications. The detection of histologically diagnosed deep ulcerations may predict a steroid-refractory course and may warrant early application of infliximab. However, larger studies are required to confirm our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000507579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506225PMC
August 2020

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study.

Clin Gastroenterol Hepatol 2020 Aug 13. Epub 2020 Aug 13.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background & Aims: Data evaluating efficacy of different doses of swallowed topical corticosteroids (STC) in the long-term management of eosinophilic esophagitis (EoE) are lacking. We assessed long-term effectiveness and safety of different STC doses for adults with EoE after achievement of histological remission.

Methods: We performed a retrospective multicenter study at five EoE referral centers (US and Switzerland). We analyzed data on 82 patients with EoE in histological remission and ongoing STC treatment with therapeutic adherence of ≥75% (58 males; mean age at diagnosis, 37.2±14.4 years). Patients were followed for a median of 2.2 years (interquartile range [IQR], 1.0-3.8 years). We collected data from 217 follow-up endoscopy visits. The primary endpoint was time to histological relapse.

Results: Histological relapse occurred in 67% of patients. Relapse rates were comparable in patients taking low dose (≤0.5 mg per day, n = 58) and high dose STC (>0.5 mg per day, n = 24) with 72 vs 54% (ns). However, histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030). There was no difference regarding rates of and time to stricture formation for low vs high dose STC. Esophageal candidiasis was observed in 6% of patients (5% for low dose, 8% for high dose, ns). No dysplasia or mucosal atrophy was detected.

Conclusion: Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2020.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108396PMC
August 2020

Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis.

Gastroenterology 2020 11 25;159(5):1672-1685.e5. Epub 2020 Jul 25.

Department of Health Services Research, Durham University, Durham, UK.

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission.

Methods: We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks.

Results: At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment.

Conclusions: In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2020.07.039DOI Listing
November 2020
-->