Showing papers by "Alain M. Schoepfer published in 2018"

Colectomy Rates in Ulcerative Colitis are Low and Decreasing: 10-year Follow-up Data From the Swiss IBD Cohort Study

Abstract: Objectives Previous population-based studies in patients with ulcerative colitis [UC] revealed variable colectomy rates and colectomy-associated risk factors. Over the past two decades, a decrease in colectomy rates was observed. We assessed risk factors and colectomy rates over time in UC in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS]. Methods Prospectively collected SIBDCS data, including disease history, baseline characteristics at enrolment, and course of disease, were retrospectively analysed. Cumulative and adjusted annual colectomy rates were calculated. Results Among 1245 UC patients analysed [54.6% male], 114 [9.2%] underwent colectomy. We observed 5-, 10-, 15-, and 20-year cumulative colectomy rates after diagnosis of 4.1%, 6.4%, 10.4%, and 14.4% of patients, respectively. Male sex (odds ratio [OR] 1.54; p = 0.035), pancolitis at diagnosis [OR = 2.16; p = 0.005], younger age at diagnosis [OR 0.89 per 5 years of age; p = 0.006] and presence of extraintestinal manifestations [EIM] [OR 2.30; p < 0.001] were risk factors for undergoing colectomy. We did not observe a significant protective effect of smoking on colectomy risk [OR 0.64; p = 0.106]. The majority of colectomies were performed within first 10 years of disease onset, with a rapidly decreasing colectomy rate after 15 years. In patients diagnosed after 2003, colectomy was performed much earlier during and individual's disease course. Nevertheless, we found a significantly decreasing trend in yearly colectomy rates over time after 2005. Conclusions Crude and adjusted colectomy rates in Swiss UC patients were lower than those reported previously in the literature, and decreased over time.

Expression Patterns of TNFα, MAdCAM1, and STAT3 in Intestinal and Skin Manifestations of Inflammatory Bowel Disease.

Abstract: Background: Pathogenesis of cutaneous extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics such as anti-integrins or JAK-inhibitors is not yet clear. Methods: We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, Hsp-27/70 on 240 intestinal (55 controls, 185 IBD) and 64 skin biopsies (11 controls, 18 Erythema nodosum (EN), 13 Pyoderma gangenosum (PG), 22 psoriasis). A semiquantitative score (0-100%) was used for evaluation. Results: TNFα was upregulated in intestinal biopsies from active Crohn`s disease (CD) vs. controls (36.2 vs. 12.1, p<0.001), but not ulcerative colitis (UC: 17.9). NFκB however was upregulated in intestinal biopsies from both active CD and UC (43.2 and 34.5 vs. 21.8, p<0.001 and p=0.017). TNFα and NFκB were overexpressed in skin biopsies from EN, PG and psoriasis. No MAdCAM1 overexpression was seen in skin tissues, while it was upregulated in active UC vs. controls (57.5 vs. 35.4, p=0.003). STAT3 was overexpressed in the intestinal mucosa of active and non-active IBD, while a similar upregulation was seen in skin biopsies from EN (84.7 vs. 22.3, p<0.001) and PG (60.5 vs. 22.3, p=0.011), but not in psoriasis. Caspase 3 and CD68 overexpression in skin biopsies distinguished EN/PG from psoriasis and controls. Conclusions: Upregulation of TNFα/NFκB in EN and PG is compatible with the efficacy of anti-TNF in EIM management. Data on overexpressed STAT3, but not MAdCAM1 support a rationale for JAK-inhibitors in EN and PG, while questioning the role of vedolizumab.

Upper Gastrointestinal Tract Involvement in Crohn's Disease: Frequency, Risk Factors, and Disease Course.

Abstract: Background The frequency of upper gastrointestinal [GI] tract involvement in Crohn`s disease [CD] has been reported with a large variation. Risk factors and disease course of patients with upper GI tract involvement remain largely elusive. Methods Data on CD patients in the Swiss Inflammatory Bowel Disease Cohort were analysed. Patients with upper GI tract involvement were compared with controls. Logistic regression models for prediction of upper GI tract involvement and Cox proportional hazard models for occurrence of complications were computed. Results We included 1638 CD patients, of whom 107 [6.5%] presented with upper GI tract involvement at the time of diagnosis and 214 [13.1%] at any time. Prevalence of such involvement at diagnosis increased over time [5.1% for 1955-95 versus 11.3% for 2009-16]. In a multivariate logistic regression model, male sex and diagnosis between 2009 and 2016 [versus before 1995] were independent predictors for presence of upper GI tract involvement at CD diagnosis (odds ratio [OR] 1.600, p = 0.021 and OR 2.686, p < 0.001, respectively), whereas adult age was a negative predictor [OR 0.388, p = 0.001]. Patients with upper GI tract involvement showed a disease course similar to control patients (hazard ratio [HR] for any complications 0.887, (95% confidence interval [CI] 0.409-1.920), and a trend towards occurrence of fewer intestinal fistulas [log-rank test p = 0.054]. Conclusions Prevalence of upper GI tract involvement has been increasing over the past decades. Male sex and young age at diagnosis were identified as the main predictive factors for such involvement at CD diagnosis. Involvement of upper GI tract did not result in a worse outcome.

Early Initiation of Anti-TNF is Associated with Favourable Long-term Outcome in Crohn's Disease: 10-Year-Follow-up Data from the Swiss IBD Cohort Study.

Abstract: BACKGROUND AND AIMS The optimal timing of treatment escalation in Crohn's disease (CD) remains a challenge and very little is known about its long-term development following early versus late administration of anti-TNF antibodies. The long-term outcome of Swiss CD patients was comparatively assessed in an up to 10-year follow-up, using patients participating in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). METHODS Prospectively-collected SIBDCS patient data, including disease history, baseline characteristics at enrolment and course of disease were analysed in patients with early versus late ( =24 months after diagnosis) and no anti-TNF treatment. RESULTS A reduced risk of developing bowel stenosis was found in patients who received early anti-TNF treatment. This association was seen in patients overall and also in the subgroups of CD patients without pre-existing complications (Log-rank test: p<0.001).Furthermore, osteoporosis and anaemia were observed significantly less frequently in patients who received early anti-TNF treatment, compared to either patients who received treatment late (p<0.001 and p=0.046, respectively) or were never (p<0.001 for both) treated with anti-TNF antibodies. Patients with early anti-TNF administration sought medical consultations significantly less often, including gastroenterologists in private practice (p=0.017), ambulatory (outpatient) hospital visits (p=0.038) and a composite of any medical visits (p=0.001). The percentage of patients unable to work was lowest for early anti-TNF treated patients, in comparison to patients who were treated late or never (3.6% versus 8.8% versus 3.7%, p=0.016). CONCLUSIONS Early anti-TNF administration was found to be associated with several indicators of a more favourable long-term outcome, in CD patients within the SIBDCS.

Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort.

Abstract: BACKGROUND AND AIM Systematic analyses of inflammatory bowel disease (IBD) drug-related side effects necessitating treatment cessation in large cohorts of patients with IBD are scarce. We aimed to assess the frequency and type of drug-related side effects requiring drug cessation in patients included in the Swiss IBD Cohort. PATIENTS AND METHODS A retrospective review was performed of data from the Swiss IBD Cohort physician questionnaires documenting a treatment cessation for the following drug categories: aminosalicylates, topical and systemic steroids, thiopurines, methotrexate, tumor necrosis factor-antagonists, and calcineurin inhibitors (tacrolimus, cyclosporine). RESULTS A total of 3192 patients were analyzed, of whom 1792 (56.1%) had Crohn's disease, 1322 (41.4%) had ulcerative colitis, and 78 (2.5%) had IBD unclassified. Of 3138 patients treated with IBD drugs, 2129 (67.8%) presented with one or several drug-related side effects necessitating drug cessation. We found a significant positive correlation between the number of concomitantly administered IBD drugs and the occurrence of side effects requiring drug cessation (P<0.001). Logistic regression modeling identified Crohn's disease diagnosis [odds ratio (OR)=1.361, P=0.017], presence of extraintestinal manifestations (OR=2.262, P<0.001), IBD-related surgery (OR=1.419, P=0.006), and the increasing number of concomitantly used IBD drugs [OR=2.007 (P<0.001) for two concomitantly used IBD drugs; OR=3.225 (P<0.001) for at least three concomitantly used IBD drugs] to be associated significantly with the occurrence of IBD drug-related adverse events that necessitated treatment cessation. CONCLUSION Physicians should keep in mind that the number of concomitantly administered IBD drugs is the main risk factor for drug-related adverse events necessitating treatment cessation.

Adults with eosinophilic oesophagitis identify symptoms and quality of life as the most important outcomes

Abstract: BACKGROUND Well informed patients who are in cohesive partnership with physicians and who have realistic expectations towards therapy are more likely to be adherent, which results in better disease control. AIM To assess which therapy goals adults with eosinophilic oesophagitis consider relevant. METHODS Following refinement during three focus groups, a study brochure and questionnaire were sent to 148 patients. Patients ranked the importance (five levels) of short-term (in the next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life (QoL), histologically-detected inflammation and fibrosis, endoscopically-detected inflammation, and stricture formation as well as achieving histological remission while asymptomatic. Patients' characteristics associated with treatment goals were identified using logistic regression. RESULTS Of 109 respondents (mean age 43 years), 85 were men. Over 90% chose symptoms and QoL improvement as important short- and long-term therapy goals. A greater proportion attributed more importance to long-term reduction in endoscopic (90% vs 73%, P < 0.001) and histological (81% vs 62%, P = 0.002) inflammation, and histologically-detected fibrosis (79% vs 64%, P = 0.018) when compared to short-term reduction in these features. Patients (88%) ranked achieving histological remission while being asymptomatic as important. Gender, therapy use, education level, QoL, symptom severity, and history of dilation were associated with patients' choice of treatment goals. CONCLUSIONS Patients attributed most importance to improvement in symptoms and QoL. Reduction in biological activity was judged less important, but more relevant in the long- compared to the short-term.

Eosinophilic esophagitis: latest insights from diagnosis to therapy

Abstract: Eosinophilic esophagitis (EoE) represents a chronic, local immune-mediated esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Other systemic and local causes of esophageal eosinophilia should be excluded. Clinical manifestations or pathologic data should not be interpreted in isolation. EoE was first described as a distinct disease entity in 1993. Most patients are diagnosed with underlying food allergies. The first diagnostic and therapeutic guidelines were published in 2007 with a first update in 2011. In 2017, new international guidelines were published based on the GRADE methodology. These guidelines provide, among many other topics, insights on the role of proton pump inhibitor-responsive esophageal eosinophilia. Over the last two decades, considerable progress was made by stakeholders regarding the understanding of EoE's pathogenesis, genetic background, natural history, allergy workup, standardization of assessment of disease activity, evaluation of minimally invasive diagnostic tools, and new therapeutic approaches. This brief review provides further insights into latest diagnostic and therapeutic advances.

Systematic analysis of annual health resource utilization and costs in hospitalized patients with inflammatory bowel disease in Switzerland

Abstract: Background and aimsReal-life data on health resource utilization and costs of hospitalized patients with inflammatory bowel disease are lacking in Switzerland. We aimed to assess health resource utilization and costs during a 1-year follow-up period starting with an index hospitalization.Patients an

Cohort Profile: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

Abstract: Background and Aims The prospective, observational Swiss Eosinophilic Esophagitis Cohort Study (SEECS) was set up in 2015 with the following goals in mind: (1) to provide up-to-date epidemiologic data; (2) to assess the appropriateness of care; (3) to evaluate the psychosocial impact; and (4) to foster translational research projects. Data capture relies on validated instruments to assess disease activity and focuses on epidemiologic variables and biosamples (esophageal biopsies and blood specimens). An annual inclusion of 70 new patients with eosinophilic esophagitis (EoE) or proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is intended. We herein describe the SEECS cohort profile. Methods The SEECS includes adult patients (age ≥18 years) with EoE or PPI-REE diagnosed according to published criteria. After inclusion, the patients are typically seen once a year for a clinical and endoscopic/histologic follow-up examination. Data are captured using validated questionnaires. Biosamples from patients with gastroesophageal reflux disease (GERD) and controls with a healthy esophagus are collected as well. Results From January 2016 to July 2017, a total of 111 patients with EoE and 10 patients with PPI-REE were recruited. In addition, esophageal biopsies and blood samples from 11 patients with GERD and 20 controls with a healthy esophagus were collected. The mean age of the patients with EoE and those with PPI-REE was 39.6 ± 12.9 and 44.6 ± 15.6 years, respectively. A male predominance was found among both the patients with EoE (77.5%) and those with PPI-REE (70%). Concomitant allergic disorders were found in 79.3% of the patients with EoE and 90% of the patients with PPI-REE. At inclusion, the EoE patients were treated with the following therapeutic regimens: no therapy (0.9%), PPI (36%), swallowed topical corticosteroids (82.9%), elimination diets (15.3%), and esophageal dilation (19.8%). Conclusions The SEECS is the first national cohort study of patients with EoE or PPI-REE. The SEECS will provide up-to-date epidemiologic data and foster translational research projects.

Assessment of endoscopic Doppler to guide hemostasis in high risk peptic ulcer bleeding.

Abstract: Introduction: Rebleeding or emergency surgery in failed endoscopic therapy of peptic ulcer bleeding are associated with high rates of morbidity and mortality. The clinical benefit of an endoscopic ...

Change of treatment modalities over the last 10 years in pediatric patients with inflammatory bowel disease in Switzerland

Abstract: BACKGROUND AND AIM During the past decade, several new drugs were approved for the treatment of pediatric inflammatory bowel disease (IBD) We aimed to evaluate if and how pharmacologic treatment options for pediatric IBD in Switzerland have changed over time PATIENTS AND METHODS Data from the pediatric Swiss IBD Cohort Study, a national prospective cohort study initiated in 2006, were analyzed Patients were divided into two groups: patients with IBD diagnosis until 2009 (168 patients) and patients with IBD diagnosis in 2010 and after (210 patients) Both groups were analyzed regarding the past and the current therapies as well as need for surgery RESULTS Overall, 378 pediatric patients with IBD were analyzed, of which 519% had Crohn's disease (CD) and 481% had ulcerative colitis/indeterminate colitis Median age at diagnosis was 12 years The majority (654%) of the patients with ulcerative colitis experienced pancolitis, whereas 454% of patients with CD presented with ileocolonic disease at diagnosis A decreased use of corticosteroids in pediatric patients with CD can be found after 2010 (P=0041) Use of 5-aminosalicylic acid for patients with CD was dramatically reduced after the year 2010 (335 vs 677% after 6 years of disease) A significant shift toward earlier use of biologicals could be shown after 2010 (P<0001) However, there was no significant decrease of surgery rate after 5 years of disease CONCLUSION In the past decade, a significant earlier use of anti-tumor necrosis factor-α agents in pediatric patients with IBD was observed with steroid-sparing effect in patients with CD However, this change was not associated with reduction of surgery

Low serum zinc levels predict presence of depression symptoms, but not overall disease outcome, regardless of ATG16L1 genotype in Crohn's disease patients.

Abstract: Background:Zinc deficiency (ZD) in Crohn’s disease (CD) is considered a frequent finding and may exacerbate CD activity. ZD is associated with depression in non-CD patients. We aimed to assess the ...

[Functional gastrointestinal disorders: update on the Rome IV criteria].

Abstract: Functional gastrointestinal disorders are highly prevalent worldwide and may have an important impact on the quality of life of affected patients. In addition, they are associated with a major socio-economic impact. In 2016 the Rome IV criteria were published that provided an update of the 2006 published Rome III criteria for functional gastrointestinal disorders. This article provides an overview of the current classification of functional gastrointestinal disorders and highlights the most important changes incorporated into the Rome IV criteria.

[Ustekinumab - Current position].

Abstract: Die vorliegende Ubersicht der IBD-Dach-Gruppe legt eine Ubersicht zu Wirkmechanismus, klinischer Entwicklung, Zulassung, Wirksamkeit und Sicherheitsaspekten des neuen Anti-p40-Antikorpers Ustekinumab vor, der fur die Therapie des moderaten bis schweren Morbus Crohn zugelassen ist. Die Arbeit fasst die aktuelle Datenlage zusammen und enthalt somit sowohl die Daten der Zulassungsstudien als auch die Daten aus kleineren und auch fachubergreifenden Arbeiten, mit denen die Aspekte zu besonderen Situationen diskutiert werden konnen. Alle Arbeiten zusammen zeigen, dass mit Ustekinumab eine wirksame und sichere Option fur den Morbus Crohn zur Verfugung steht.