Author: "Stéphane Nancey" / Topic: crohn's disease - Searchworks@Jio Institute Digital Library Search Results

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1. Prevalence of the Oral Corticosteroid Exposure and Excessive Use in Patients with Inflammatory Bowel Disease: Data from Four French Referral Centers of the International DICE Study

Author: Stéphane Nancey, Xavier Hébuterne, Cyrielle Gilletta, Evguenia Hacques, and Xavier Roblin
Subjects: corticosteroids, Crohn’s disease, inflammatory bowel disease, ulcerative colitis, Medicine
Abstract: Background: Corticosteroids used to induce a response in Crohn’s disease (CD) and ulcerative colitis (UC) may cause adverse reactions. The DICE study aimed to quantify and investigate factors associated with their use. Methods: This cross-sectional, non-interventional study conducted in seven countries allowed us to collect data on oral corticosteroid exposure and excessive use (cf. British Society of Gastroenterology) over the past 12 months in adult patients with CD or UC for more than a year. The factors associated with these practices were investigated using marginal logistic models. We present the results from the four participating French expert centers. Results: Corticosteroid exposure over the past 12 months was observed in 20.1% of 324 CD patients and 30.2% of 205 UC patients. Excessive use was reported in 13.3% and 17.1% of patients, respectively. Corticosteroid exposure and excessive use were less frequently observed in CD than in UC (OR: 0.56, p < 0.0001, and 0.69, p = 0.0042). A disease activity assessment at patient’s last visit was the main factor (p < 0.01) associated with the risk of corticosteroid exposure and excessive use in CD (OR: 3.41 and 3.44) and UC (OR: 7.29 and 6.90). Conclusions: Corticosteroid exposure and excessive use continue to be frequently observed in CD and UC in France.
Published: 2024
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2. The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics

Author: Margaux Lelong, Régis Josien, Marianne Coste-Burel, Marie Rimbert, Céline Bressollette-Bodin, Stéphane Nancey, Guillaume Bouguen, Matthieu Allez, Mélanie Serrero, Ludovic Caillo, Cléa Rouillon, Pierre Blanc, David Laharie, Raphaël Olivier, Laurent Peyrin-Biroulet, Nina Dib, Astrid De Maissin, Céline Montuclard, Caroline Trang-Poisson, Fabienne Vavasseur, Géraldine Gallot, Mathilde Berthome, Cécile Braudeau, Justine Chevreuil, Arnaud Bourreille, and Catherine Le Berre
Subjects: Crohn’s disease, ulcerative colitis, infliximab, vedolizumab, SARS-CoV-2, trough levels, Immunologic diseases. Allergy, RC581-607
Abstract: BackgroundPatients with inflammatory bowel disease (IBD) may have a modified immune response to SARS-CoV-2. The objectives were to evaluate the prevalence of COVID-19 in patients treated with infliximab or vedolizumab, to analyze the factors associated with the infection, the impact of treatments and trough levels.MethodsPatients with IBD treated with intravenous biologics in 14 French centers were included between March and June 2020 and followed-up for 6 months. Blood samples were collected for serologies and trough levels. The analysis of factors associated with COVID-19 was conducted in a matched 1:1 case-control sub-study with positive patients.ResultsIn total, 1026 patients were included (74.9% infliximab). Over the follow-up period, 420 patients reported the occurrence of COVID-19 symptoms; 342 had been tested of whom 18 were positive. At the end of follow-up, 38 patients had a positive serology. Considering both nasal tests and serologies together, 46 patients (4.5%) had been infected. The risk of COVID-19 was related neither to the use of treatments (whatever the trough levels) nor to disease activity. Infections were more frequent when using public transport or living in flats in urban areas.ConclusionsThe prevalence rate of COVID-19 in this IBD population treated with intravenous infliximab or vedolizumab was the same as the one in the French population before the start of the vaccination campaign. The risk was increased by urban living and was not influenced by disease activity or biologics. Sanitary barrier measures remain the best way to protect against SARS-CoV-2 in patients with IBD in biological therapy.
Published: 2023
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3. Serum calprotectin is useful to confirm inflammatory bowel disease activity but not to predict relapse

Author: Pauline Veyrard, Xavier Roblin, Céline Pansart, Ren Mao, Stéphane Nancey, Martin Killian, Louis Waeckel, Anne-Emmanuelle Berger, Nicolas Williet, Laetitia Bastide, Mathilde Barrau, Quentin Tournier, and Stéphane Paul
Subjects: Serum calprotectin, Inflammatory bowel diseases, Crohn's disease, Ulcerative colitis, Relapse, Mucosal healing, Immunologic diseases. Allergy, RC581-607
Abstract: Aim: Serum calprotectin (SC), a novel biomarker of inflammatory bowel diseases (IBD), has been recently investigated with conflicting results. The purpose of this study was to assess the ability of SC to predict relapse in IBD patients treated by biologic therapies, and to evaluate the correlation between SC, clinical and endoscopic relapse and other biomarkers as fecal calprotectin (FC) and C-reactive protein (CRP). Methods: All consecutive IBD patients in deep remission (clinical, endoscopic or imaging remission) were followed 12 months in this prospective study. Blood and stool samples were collected for SC, serum CRP and FC. SC was measured the day of inclusion (baseline, D0), 3 months (M3) and at 6 months (M6) or during the study period for clinical relapse. Relapse was defined as clinical, biomarkers, or endoscopic/imaging activities. Evolution of SC was quantified before relapse to analyze a predicting value of loss of response (LOR). SC for patients with active IBD and those with symptoms without inflammation were also compared. Results: Among the 119 patients included, 54 (46.4%) patients experienced a disease relapse during follow-up. Median SC levels did not increase in patients with clinical relapse (3.15 µg/ml at baseline, 3.38 µg/ml at M3, 3.33 µg/ml at M6 and 3.99 µg/ml in case of relapse (p = 0.63)). SC were compared during relapse in patients with endoscopic remission but clinical symptoms defined as secondary Irritable Bowel Syndrome (IBS). SC levels were higher in active IBD and similar between the groups of patients with IBS or deep remission (3.05 µg/ml IBS vs 2.99 µg/ml remission vs 5.1 µg/ml for clinical relapse, p = 0.04). In patients with clinical symptoms, SC presents a good predictive value for relapse (AUROC 0.764, IC95: 0.68–0.88), with a sensitivity of 72%, a specificity of 77%, using a cut-off value of 4.45 µg/ml. A weak, but significant correlation was found between SC and FC levels (r = 0.35, P = 0.001). A combined score with CRP, FC and SC is not efficient to improve IBD diagnostic. Conclusion: SC was significantly higher in patients with clinical relapse compared to those with endoscopic remission with or without clinical symptoms. SC allow to discriminate patients with active IBD or with IBS but failed to predict relapse.
Published: 2022
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4. Fecal microbiota and bile acids in IBD patients undergoing screening for colorectal cancer

Author: Aonghus Lavelle, Stéphane Nancey, Jean-Marie Reimund, David Laharie, Philippe Marteau, Xavier Treton, Matthieu Allez, Xavier Roblin, Georgia Malamut, Cyriane Oeuvray, Nathalie Rolhion, Xavier Dray, Dominique Rainteau, Antonin Lamaziere, Emilie Gauliard, Julien Kirchgesner, Laurent Beaugerie, Philippe Seksik, Laurent Peyrin-Biroulet, and Harry Sokol
Subjects: Gut microbiota, inflammatory bowel disease, dysplasia, colitis-associated colorectal cancer, crohn’s disease, ulcerative colitis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Due to the potential role of the gut microbiota and bile acids in the pathogenesis of both inflammatory bowel disease (IBD) and sporadic colorectal cancer, we aimed to determine whether these factors were associated with colorectal cancer in IBD patients. 215 IBD patients and 51 non-IBD control subjects were enrolled from 10 French IBD centers between September 2011 and July 2018. Fecal samples were processed for bacterial 16S rRNA gene sequencing and bile acid profiling. Demographic, clinical, endoscopic, and histological outcomes were recorded. Characteristics of IBD patients included: median age: 41.6 (IQR 22); disease duration 13.2 (13.1); 47% female; 21.9% primary sclerosing cholangitis; 109 patients with Crohn’s disease (CD); 106 patients with ulcerative colitis (UC). The prevalence of cancer was 2.8% (6/215: 1 CD; 5 UC), high-grade dysplasia 3.7% (8/215) and low-grade dysplasia 7.9% (17/215). Lachnospira was decreased in IBD patients with cancer, while Agathobacter was decreased and Escherichia-Shigella increased in UC patients with any neoplasia. Bile acids were not associated with cancer or neoplasia. Unsupervised clustering identified three gut microbiota clusters in IBD patients associated with bile acid composition and clinical features, including a higher risk of neoplasia in UC in two clusters when compared to the third (relative risk (RR) 4.07 (95% CI 1.6–10.3, P
Published: 2022
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5. Relationships of circulating CD4+ T cell subsets and cytokines with the risk of relapse in patients with Crohn’s disease

Author: Rémi Duclaux-Loras, Gilles Boschetti, Bernard Flourie, Xavier Roblin, Jean-Benoit Leluduec, Stéphane Paul, Thibaut Almeras, Karine Ruel, Anthony Buisson, Jacques Bienvenu, Cendrine Josson, Renaud Jasnowski, Stéphane Legastelois, Arnaud Foussat, Camille Meunier, Christophe Viret, Aurore Rozieres, Mathias Faure, Dominique Kaiserlian, and Stéphane Nancey
Subjects: Crohn’s disease, CD4+ T cells, FOXP3, interleukin 17A, relapse, Immunologic diseases. Allergy, RC581-607
Abstract: Background and aimsWe aimed to analyze circulating CD4+ T cell subsets and cytokines during the course of Crohn’s disease (CD).Methods and resultsCD4+ T cell subsets, ultrasensitive C-reactive protein (usCRP), and various serum cytokines (IL-6, IL-8, IL-10, IL-13, IL-17A, IL-23, TNFα, IFNγ, and TGFβ) were prospectively monitored every 3 months for 1 year, using multicolor flow cytometry and an ultrasensitive Erenna method in CD patients in remission at inclusion. Relapse occurred in 35 out of the 113 consecutive patients (31%). For patients in remission within 4 months prior to relapse and at the time of relapse, there was no significant difference in Th1, Th17, Treg, and double-positive CD4+ T cell subsets co-expressing either IFNγ and FOXP3, IL-17A and FOXP3, or IFNγ and IL-17A. On the contrary, in patients who remained in remission, the mean frequency and number of double-positive IL-17A+FOXP3+ CD4+ T cells and the level of usCRP were significantly higher (p ≤ 0.01) 1 to 4 months prior to relapse. At the time of relapse, only the IL-6 and usCRP levels were significantly higher (p ≤ 0.001) compared with those patients in remission. On multivariate analysis, a high number of double-positive IL-17A+FOXP3+ CD4+ T cells (≥1.4 cells/mm3) and elevated serum usCRP (≥3.44 mg/L) were two independent factors associated with risk of relapse.ConclusionsDetection of circulating double-positive FOXP3+IL-17A+ CD4+ T cell subsets supports that T cell plasticity may reflect the inflammatory context of Crohn’s disease. Whether this subset contributes to the pathogenesis of CD relapse needs further studies.
Published: 2022
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6. Prevalence of Yersinia Species in the Ileum of Crohn's Disease Patients and Controls

Author: Guillaume Le Baut, Claire O'Brien, Paul Pavli, Maryline Roy, Philippe Seksik, Xavier Tréton, Stéphane Nancey, Nicolas Barnich, Madeleine Bezault, Claire Auzolle, Dominique Cazals-Hatem, Jérome Viala, Matthieu Allez, The REMIND GROUP, Jean-Pierre Hugot, and Anne Dumay
Subjects: yersinia, Crohn's disease, gut microbiota, ileal mucosa, innate immunity, mucosal immune system, Microbiology, QR1-502
Abstract: Yersinia are common contaminants of food products, but their prevalence in the human gut is poorly documented. Yersinia have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gyrB gene of Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and the inv gene of Y. pseudotuberculosis. We analyzed a total of 470 ileal samples taken from 338 participants (262 CD patients and 76 controls) belonging to three independent cohorts. All patients and controls were phenotyped and genotyped for the main CD susceptibility variants: NOD2, ATG16L1, and IRGM. Yersinia were found in 7.7% of ileal samples (respectively 7.9 and 7.6% in controls and CD patients) corresponding to 10% of participants (respectively 11.8 and 9.5% in controls and CD patients). Y. enterocolitica, Y. pseudotuberculosis and Y. intermedia were the most frequently identified species. The bacteria were more frequent in resected specimens, lymph nodes and Peyer's patches. Yersinia were no more likely to be detected in CD tissues than tissues from inflammatory and non-inflammatory controls. CD patients treated with immunosuppressants were less likely to be Yersinia carriers. In conclusion, this work shows that Yersinia species are frequently found at low levels in the human ileum in health and disease. The role of Yersinia species in this ecosystem should now be explored.
Published: 2018
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7. Use of imaging modalities for decision-making in inflammatory bowel disease

Author: Stéphane Nancey, Mathurin Fumery, Mathias Faure, Gilles Boschetti, Claire Gay, Laurent Milot, Xavier Roblin, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Université de La Réunion - UFR Santé (UR UFRS), Université de La Réunion (UR), Hôpital Edouard Herriot [CHU - HCL], Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Crohn’s disease, ultrasound, Gastroenterology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MRI, clinical decision, ulcerative colitis
Abstract: Cross-sectional magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS) provide valuable and noninvasive information to accurately assess disease activity, severity, and extent; detect complications; and monitor the response to treatment, as well as predict the postoperative recurrence of Crohn’s disease and a negative disease course. Therefore, both imaging modalities are emerging as pivotal diagnostic tools to achieve the emerging therapeutic target of transmural healing associated with better disease outcomes. Despite its numerous potential advantages over endoscopy and even MRE and its good availability, IUS is still widely underused to monitor and manage inflammatory bowel disease (IBD) patients and help in making clinical decisions in routine practice. This situation is clearly due to the absence of validated, reliable, and responsive indices, as well as the lack of trained gastroenterologists and radiologists, as IUS is a component of radiologist expertise in several countries but not yet integrated into the training program of gastroenterologists. However, there is an increasing body of evidence in the literature that IUS and MRE are both becoming essential imaging resources to help clinicians in making reliable decisions. Here, we discuss the up-to-date evidence about the usefulness and performance of cross-sectional imaging, focusing on the ability of bowel US and MRE to aid clinical decision-making for the optimal management and monitoring of IBD.
Published: 2023

8. Adalimumab in biologic-naïve patients with Crohn’s disease after resolution of an intra-abdominal abscess: a prospective study from the GETAID

Author: Yoram Bouhnik, Guillaume Pineton de Chambrun, Jérôme Lambert, Maria Nachury, Philippe Seksik, Romain Altwegg, Lucine Vuitton, Carmen Stefanescu, Stéphane Nancey, Alexandre Aubourg, Mélanie Serrero, Jérôme Filippi, Kristell Desseaux, Stéphanie Viennot, Vered Abitbol, Madina Boualit, Arnaud Bourreille, Cyrielle Giletta, Anthony Buisson, Xavier Roblin, Nina Dib, Georgia Malamut, Aurélien Amiot, Mathurin Fumery, Edouard Louis, Yasmine Elgharabawy, Laurent Peyrin-Biroulet, Jacques Moreau, Xavier Treton, Charlotte Mailhat, Justine Pollet, Carole Martins, Guillaume Savoye, Noémie Tavernier, Jean-Yves Mary, Magali Zappa, Claire Painchart, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hopital Saint-Louis [AP-HP] (AP-HP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Nord [CHU - APHM], Centre Hospitalier Universitaire de Nice (CHU Nice), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), and Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: Crohn’s disease, surgery, Hepatology, adalimumab, Gastroenterology, abscess, anti-TNF, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background & aims: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in CD patients with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success.Methods: A multicenter, prospective study was conducted in biologic-naïve CD patients with resolved intra-abdominal abscess treated with ADA with a two-year follow-up. The primary endpoint was ADA failure at W24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a cox regression, respectively.Results: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight (50%) patients were male and the median age at baseline was 28 years. At W24, 87 (74%, 95%CI: 65.5-82.0, n=117) patients achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72·9% (95%CI: 62.1-79.8, n=109). Abscess drainage was significantly associated with ADA failure at W24 (OR=4.18; 95%CI: 1.06-16.5; p=0.043). Disease duration (HR=1.32, 95%CI: 1.09-1.59, p=0.008), abscess drainage (HR=5.59, 95%CI: 2.21-14.15, p=0.001), and inflammatory changes in mesenteric fat (HR=0.4, 95%CI: 0.17-0.94, p=0.046) were significantly associated with ADA failure at W104.Conclusion: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess.
Published: 2023

9. Faster and less invasive tools to identify patients with ileal colonization by adherent‐invasive E. coli in Crohn's disease

Author: Clara Yzet, Anthony Buisson, Elisabeth Billard, Benjamin Pariente, Caroline Chevarin, Jérôme Filippi, Philippe Seksik, Nicolas Barnich, Laurent Peyrin-Biroulet, Gilles Bommelaer, Emilie Vazeille, Marion Goutte, Gilles Boschetti, Mathurin Fumery, Stéphane Nancey, Maria Nachury, Anaëlle Dubois, Bruno Pereira, Nathalie Ballet, Matthieu Allez, Stéphanie Rodriguez, Xavier Hébuterne, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Amiens-Picardie, CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lesaffre, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], Hôpital Claude Huriez [Lille], INRAeUSC-2018Clermont Auvergne UniversityLesaffre InternationalMinistere de la Recherche et de la TechnologieI-SITE projectCAP 2025, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, Saliva, anti-E, Biopsy, adherent‐invasive E. coli, Gastroenterology, Inflammatory bowel disease, Feces, 0302 clinical medicine, Crohn Disease, Prospective Studies, Intestinal Mucosa, 0303 health sciences, Crohn's disease, biology, medicine.diagnostic_test, Colonoscopy, Antibodies, Bacterial, CEACAM6. IBD, medicine.anatomical_structure, Oncology, Biomarker (medicine), Female, Original Article, 030211 gastroenterology & hepatology, Antibody, adherent-invasive E, medicine.medical_specialty, IBD, Ileum, 03 medical and health sciences, inflammatory bowel disease, Internal medicine, Escherichia coli, medicine, anti‐E. coli antibodies, Humans, CEACAM6, 030304 developmental biology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, coli, coli antibodies, biology.protein, business, Biomarkers
Abstract: International audience; Background and AimsThe identification of Crohn's disease (CD)-associated adherent and invasive Escherichia coli (AIEC) is time-consuming and requires ileal biopsies. We aimed to identify a faster and less invasive methods to detect ileal colonization by AIEC in CD patients.MethodsCD patients requiring ileo-colonoscopy were consecutively enrolled in this prospective multicenter study. Samples from saliva, serum, stools, and ileal biopsies of CD patients were collected.ResultsAmong 102 CD patients, the prevalence of AIEC on ileal biopsies was 24.5%. The abundance and global invasive ability of ileal-associated total E. coli were respectively ten-fold (p = 0.0065) and two-fold (p = 0.0007) higher in AIEC-positive (vs. AIEC-negative), while abundance of total E. coli in the feces was not correlated with AIEC status in the ileum. The best threshold of ileal total E. coli was 60 cfu/biopsy to detect AIEC-positive patients, with high negative predictive value (NPV) (94.1%[80.3–99.3]), while the global invasive ability (>9000 internalized bacteria) was able to detect the presence of AIEC with high positive predictive value (80.0% [55.2–100.0]). Overall, 78.1% of the AIEC + patients were colonized by two or less different AIEC strains. The level of serum anti-total E. coli antibodies (AEcAb) was higher in AIEC-positive patients (p = 0.038) with a very high negative predictive value (96.6% [89.9–100.0]) (p = 0.038) for a cut-off value > 1.9 × 10−3.ConclusionsMore than two thirds of AIEC-positive CD patients were colonized by two or less AIEC strains. While stools samples are not accurate to screen AIEC status, the AEcAb level appears to be an attractive, rapid and easier biomarker to identify patients with Crohn's disease harboring AIEC.
Published: 2021

10. IgA vasculitis in patients with inflammatory bowel disease: new insights into the role of TNF-α blockers

Author: Cécile Audrey Durel, Guillaume Moulis, Mathurin Fumery, Vered Abitbol, Stéphane Nancey, Groupe français d’étude des vascularites, Marie-Christine Martinez Vinson, Khalil El Karoui, Viviane Queyrel-Moranne, Christian Agard, Alexis Régent, Stéphane Koch, Benjamin Terrier, Didier Ducloux, Anne-Gaëlle Kervegant, Laurent Peyrin Biroulet, David Laharie, Anne Bourrier, Michael T. Collins, Lucine Vuitton, Cédric Rafat, Loïc Guillevin, Romain Paule, Mickaela Voicu, Camille Rasmussen, François Aubin, François Maurier, Caroline Morbieu, Nizar Joher, Tali Anne Szwebel, and Bénédicte Pigneur
Subjects: Vasculitis, medicine.medical_specialty, IgA Vasculitis, Cyclophosphamide, Antineoplastic Agents, Gastroenterology, Inflammatory bowel disease, Rheumatology, Recurrence, Internal medicine, medicine, Humans, Pharmacology (medical), Retrospective Studies, Crohn's disease, Tumor Necrosis Factor-alpha, business.industry, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Immunoglobulin A, Discontinuation, IgA vasculitis, Tumor Necrosis Factor Inhibitors, Complication, business, medicine.drug
Abstract: Objective The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α therapy. We aimed to describe the association of IgAV and IBD. Methods We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. Results Forty-three cases were included. IBD [mainly Crohn’s disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4–15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-α for a median duration of 31.5 (IQR 19–56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). Conclusions This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse.
Published: 2021

11. Defining and Assessing the Reproducibility of Crohn’s Disease Endoscopic Lesions: A Delphi-like Method from the GETAID

Author: Lucine Vuitton, Edouard Louis, G Pineton de Chambrun, Anne-Laure Pelletier, P. Marteau, A. Buisson, D. Laharie, P. Seksik, Gwenola Vernier-Massouille, Yoram Bouhnik, Aurelien Amiot, Jean-Yves Mary, Jérôme Filippi, Driffa Moussata, Laurent Peyrin-Biroulet, Guillaume Cadiot, Mathieu Allez, Jean-Louis Dupas, Stéphane Nancey, Alain Attar, Maria Nachury, Antoine Blain, Université Clermont Auvergne (UCA), Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Henri Mondor d'Aurillac, Centre Hospitalier Universitaire de Reims (CHU Reims), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Beaujon [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Tourcoing, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Amiens-Picardie, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Centre Hospitalier Universitaire de Liège (CHU-Liège)
Subjects: Crohn’s disease, MESH: Terminology as Topic, Delphi Technique, [SDV]Life Sciences [q-bio], MESH: Observer Variation, Severity of Illness Index, Endoscopy, Gastrointestinal, MESH: Delphi Technique, MESH: Quality Improvement, Crohn Disease, Terminology as Topic, MESH: Severity of Illness Index, medicine, Humans, reproducibility, Observer Variation, Crohn's disease, Microscopy, Video, MESH: Humans, MESH: Crohn Disease, business.industry, Gastroenterology, Reproducibility of Results, General Medicine, ulcerations, medicine.disease, Quality Improvement, endoscopic lesions, MESH: Endoscopy, Gastrointestinal, Intestines, MESH: Microscopy, Video, MESH: Reproducibility of Results, business, Nuclear medicine, MESH: Intestines
Abstract: Background and Aims Defining and assessing the reproducibility of Crohn’s disease [CD] endoscopic lesions is essential in assessing endoscopic healing. Methods Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as ‘moderate’ [0.4–0.6], ‘substantial’ [0.6–0.8], or ‘almost perfect’ [0.8–1.0]. Results Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing ‘substantial’ agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from ‘moderate’ to ‘almost perfect’ agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. Conclusions Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided ‘substantial’ inter-observer agreements, especially in case of high-quality videos.
Published: 2020

12. Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

Author: Lieven Pouillon, Guillaume Bouguen, Bernard Flourié, Mathurin Fumery, Stephanie Viennot, Laurent Siproudhis, Franck Brazier, Jérôme Filippi, Pauline Veyrard, Florian Poullenot, Anthony Buisson, Lucile Boivineau, Xavier Treton, Momar Diouf, David Laharie, Cyrielle Gilletta, Stéphane Nancey, Romain Altwegg, Xavier Roblin, Anne Bozon, and Laurent Peyrin-Biroulet
Subjects: medicine.medical_specialty, Crohn's disease, medicine.diagnostic_test, business.industry, Gastroenterology, Colonoscopy, General Medicine, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Ustekinumab, medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, Every Four Weeks, Calprotectin, Adverse effect, business, medicine.drug, Cohort study
Abstract: Background The approved maintenance regimens for ustekinumab in Crohn’s disease [CD] are 90 mg every 8 or 12 weeks. Some patients will respond partially to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections. Methods All patients with active CD, as defined by Harvey–Bradshaw score ≥ 4 and one objective sign of inflammation [C-reactive protein > 5 mg/L and/or faecal calprotectin > 250 µg/g and/or radiological and/or endoscopic evidence of disease activity] who required ustekinumab dose escalation to 90 mg every 4 weeks for loss of response or incomplete response to ustekinumab 90 mg every 8 weeks were included in this retrospective multicentre cohort study. Results One hundred patients, with a median age of 35 years [interquartile range, 28–49] and median disease duration of 12 [7–20] years were included. Dose intensification was performed after a median of 5.0 [2.8–9.0] months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 [1.3–3.0] months. After a median follow-up of 8.2 [5.6–12.4] months, 61% of patients were still treated with ustekinumab, and 26% were in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission [no ulcers]. At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events. Conclusion In this multicentre study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.
Published: 2020

13. Surgery for Crohn’s disease during pregnancy: A nationwide survey

Author: Jérémie H. Lefevre, Laura Beyer-Berjot, Laurent Bresler, Aurelien Amiot, Anthony Buisson, P. Zerbib, Getaid Chirurgie, Adeline Germain, David Laharie, Carmen Stefanescu, Thomas Chateau, Stéphane Nancey, Laurent Peyrin-Biroulet, and Zaher Lakkis
Subjects: Adult, Pediatrics, medicine.medical_specialty, Clinical Decision-Making, MEDLINE, Gestational Age, Disease, Nationwide survey, Severity of Illness Index, Young Adult, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Crohn Disease, Pregnancy, Birth Weight, Humans, Medicine, Perinatal Mortality, Retrospective Studies, Crohn's disease, business.industry, Infant, Newborn, Pregnancy Outcome, Editorials, Gastroenterology, Colonoscopy, Original Articles, medicine.disease, Surgery, Pregnancy Complications, Expectant mothers, Maternal Mortality, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, business
Abstract: BACKGROUND AND AIMS: Crohn’s disease (CD) frequently affects young women and may require surgery during pregnancy. Data regarding operation for CD in expectant mothers are scare. MATERIALS AND METHODS: This was a retrospective nationwide survey from the GETAID Chirurgie. Any woman with CD undergoing surgery during pregnancy was eligible. RESULTS: A total of 15 cases were collected between 1992 and 2015. Most operations were performed due to penetrating or stricturing complications. Mean gestational age at delivery was 34 weeks, with a mean birth weight of 2507 g. Maternal post-operative complications occurred in two-thirds of cases. Maternal mortality rate was 6.7% and neonatal mortality rate 9.1%. CONCLUSIONS: This is the largest case series of surgery for CD during pregnancy. This operation may have significant morbidity and mortality for mother, fetus, and newborn. Indication needs to be tailored to maternal status, disease severity, and gestational age. Surgery should be managed by experienced gynecologists, physicians, and surgeons. Active CD may be associated with a greater risk to the fetus than the surgical procedure itself.
Published: 2020

14. Endoscopic Postoperative Recurrence in Crohn's Disease After Curative Ileocecal Resection with Early Prophylaxis by Anti-TNF, Vedolizumab or Ustekinumab: A Real-World Multicentre European Study

Author: Henit Yanai, Anna Kagramanova, Oleg Knyazev, João Sabino, Shana Haenen, Gerassimos J Mantzaris, Katerina Mountaki, Alessandro Armuzzi, Daniela Pugliese, Federica Furfaro, Gionata Fiorino, David Drobne, Tina Kurent, Sharif Yassin, Nitsan Maharshak, Fabiana Castiglione, Roberto de Sire, Olga Maria Nardone, Klaudia Farkas, Tamas Molnar, Zeljko Krznaric, Marko Brinar, Elena Chashkova, Moran Livne Margolin, Uri Kopylov, Cristina Bezzio, Ariella Bar-Gil Shitrit, Milan Lukas, María Chaparro, Marie Truyens, Stéphane Nancey, Triana Lobaton, Javier P Gisbert, Simone Saibeni, Péter Bacsúr, Peter Bossuyt, Julien Schulberg, Frank Hoentjen, Chiara Viganò, Andrea Palermo, Joana Torres, Joana Revés, Konstantinos Karmiris, Magdalini Velegraki, Edoardo Savarino, Panagiotis Markopoulos, Eftychia Tsironi, Pierre Ellul, Cristina Calviño Suárez, Roni Weisshof, Dana Ben-Hur, Timna Naftali, Carl Eriksson, Ioannis E Koutroubakis, Kalliopi Foteinogiannopoulou, Jimmy K Limdi, Eleanor Liu, Gerard Surís, Emma Calabrese, Francesca Zorzi, Rafał Filip, Davide Giuseppe Ribaldone, Yifat Snir, Idan Goren, Hagar Banai-Eran, Yelena Broytman, Hadar Amir Barak, Irit Avni-Biron, Jacob E Ollech, Iris Dotan, and Maya Aharoni Golan
Subjects: Adult, Male, Crohn’s disease, Biological Products, post-operative recurrence, Gastroenterology, General Medicine, Biologics, biologics, Young Adult, Treatment Outcome, Post-operative recurrence, Crohn Disease, Medicine and Health Sciences, Humans, Female, Tumor Necrosis Factor Inhibitors, Ustekinumab, 03.02.18. Endokrinológia és anyagcserebetegségek (benne cukorbetegség, hormonok), Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Retrospective Studies
Abstract: Background Endoscopic-post-operative-recurrence [ePOR] in Crohn’s disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. Methods A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. Results The study included 297 patients (53.9% males, age at diagnosis 24 years [19–32], age at ICR 34 years [26–43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01–2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25–1.19], OR = 1.86 [95% CI: 0.79–4.38]), respectively. Conclusion Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.
Published: 2022

15. Impact of HIV Infection on the Course of Inflammatory Bowel Disease and Drug Safety Profile: A Multicenter GETAID Study

Author: Lucas Guillo, David Laharie, Mélanie Serrero, Anne-Laure Pelletier, Hélène Rousseau, Laurent Peyrin-Biroulet, Mathieu Uzzan, Christian Rabaud, Stephanie Viennot, Laurence Picon, Vered Abitbol, Mathias Vidon, Ludovic Caillo, Aurelien Amiot, Laurent Beaugerie, Morgane Amil, Maria Nachury, Jérôme Filippi, Jean-Marc Gornet, Stéphane Nancey, Romain Altwegg, Michael T. Collins, Catherine Reenaers, Felix Goutorbe, Alban Benezech, Grégory Dubourg, Anthony Buisson, Cédric Baumann, Hôpital Nord [CHU - APHM], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Bordeaux [Bordeaux], Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier de la Côte Basque (CHCB), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Henri Duffaut (Avignon), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Délégation à la Recherche Clinique et à l'Innovation [CHRU Nancy] (DRCI), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, medicine.medical_specialty, [SDV]Life Sciences [q-bio], HIV Infections, Disease, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Intestinal mucosa, Crohn Disease, Internal medicine, medicine, Humans, Retrospective Studies, Crohn's disease, Hepatology, business.industry, Hazard ratio, Gastroenterology, Retrospective cohort study, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 030220 oncology & carcinogenesis, Concomitant, 030211 gastroenterology & hepatology, Colitis, Ulcerative, business
Abstract: Background and aims Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), and human immunodeficiency virus (HIV) both impact innate and adaptive immunity in the intestinal mucosa. As it is a rare situation, the intersection between HIV and IBD remains unclear, especially the impact of HIV infection on the course of IBD, and the drug safety profile is unknown. Methods We conducted a multicenter retrospective cohort study between January 2019 and August 2020. All adult patients with IBD and concomitant HIV infection were included. Each IBD patient with HIV was matched to two HIV-uninfected IBD patients. Results Overall, 195 patients with IBD were included, including 65 HIV-infected patients and 130 without HIV infection. Of the 65 infected patients, 22 (33.8%) required immunosuppressants and 31 (47.7%) biologics. In the HIV-infected group, the need for immunosuppressants (p = 0.034 for CD and p = 0.012 for UC) and biologics (p = 0.004 for CD and p = 0.008 for UC) was significantly lower. The disease course, using a severity composite criterion, was not significantly different between the two groups for CD (hazard ration (HR) = 1.3 [0.7; 2.4], p = 0.45) and UC (HR, 1.1 [0.5; 2.7], p = 0.767). The overall drug safety profile was statistically similar between the two groups. Conclusion Although HIV-infected patients receive less treatments, the course of their IBD did not differ than uninfected, suggesting that HIV infection might attenuate IBD. The drug safety profile is reassuring, allowing physician to treat these patients according to current recommendations.
Published: 2022

16. Comparative acceptability of therapeutic maintenance regimens in patients with inflammatory bowel disease: results from the nationwide ACCEPT2 Study

Author: Anthony Buisson, Mélanie Serrero, Laurie Orsat, Stéphane Nancey, Pauline Rivière, Romain Altwegg, Laurent Peyrin-Biroulet, Maria Nachury, Xavier Hébuterne, Cyrielle Gilletta, Mathurin Flamant, Stéphanie Viennot, Guillaume Bouguen, Aurélien Amiot, Stéphane Mathieu, Lucine Vuitton, Laurianne Plastaras, Arnaud Bourreille, Ludovic Caillo, Félix Goutorbe, Guillaume Pineton De Chambrun, Alain Attar, Xavier Roblin, Bruno Pereira, Mathurin Fumery, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Gastro-entérologie [CHU Hôpital Nord - Marseille], Hôpital Nord [CHU - APHM]-Assistance publique Hôpitaux de Marseille (APHM), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Toulouse [Toulouse], Clinique Jules-Vernes [Nantes], Clinique de l'Alma, Paris, France., Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Elsan Pôle Santé République, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CH Colmar, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Le CHCB, Centre Hospitalier de la Côte Basque, Clinique du Parc, Clinique Internationale du Parc Monceau, CHU Saint-Etienne, Unité de Biostatistiques [CHU Clermont-Ferrand], Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Pfizer, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de la Côte Basque (CHCB), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Crohn’s disease, small molecules, acceptability, Gastroenterology, Immunology and Allergy, biologics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ulcerative colitis
Abstract: Background Owing to growing number of therapeutic options with similar efficacy and safety, we compared the acceptability of therapeutic maintenance regimens in inflammatory bowel disease (IBD). Methods From a nationwide study (24 public or private centers), IBD patients were consecutively included for 6 weeks. A dedicated questionnaire including acceptability numerical scales (ANS) ranging from 0 to 10 (highest acceptability) was administered to both patients and related physicians. Results Among 1850 included patients (65.9% with Crohn’s disease), the ANS were 8.68 ± 2.52 for oral route (first choice in 65.8%), 7.67 ± 2.94 for subcutaneous injections (first choice in 21.4%), and 6.79 ± 3.31 for intravenous infusions (first choice in 12.8%; P < .001 for each comparison). In biologic-naïve patients (n = 315), the most accepted maintenance regimens were oral intake once (ANS = 8.8 ± 2.2) or twice (ANS = 6.9 ± 3.4) daily and subcutaneous injections every 12 or 8 weeks (ANS = 7.9 ± 3.0 and ANS = 7.2 ± 3.2, respectively). Among 342 patients with prior exposure to subcutaneous biologics, the preferred regimens were subcutaneous injections (≥2 week-intervals; ANS between 9.1 ± 2.3 and 8.1 ± 2.7) and oral intake once daily (ANS = 7.7 ± 3.2); although it was subcutaneous injections every 12 or 8 weeks (ANS = 8.4 ± 3.0 and ANS = 8.1 ± 3.0, respectively) and oral intake once daily (ANS = 7.6 ± 3.1) in case of prior exposure to intravenous biologics (n = 1181). The impact of usual therapeutic escalation or de-escalation was mild (effect size Conclusions Although oral intake is overall preferred, acceptability is highly impacted by the rhythm of administration and prior medication exposures. However, SC treatment with long intervals between 2 injections (≥8 weeks) and oral intake once daily seems to be the most accepted modalities.
Published: 2022

17. Usefulness of confocal laser endomicroscopy for predicting postoperative recurrence in patients with Crohn’s disease: a pilot study

Author: Julie Auzoux, Pierre Besson, Gilles Boschetti, Alexandre Aubourg, Sébastien Roger, Morgane Caulet, Thierry Lecomte, Benjamin Anon, Bernard Flourié, Laurence Picon, Driffa Moussata, Stéphane Nancey, Lucile Poisson, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hépato-Gastro-Onco-Entérologie [CHRU de Tours], Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Colon, medicine.medical_treatment, Population, Colonoscopy, Pilot Projects, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Gastroenterology, Inflammatory bowel disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Ileum, Recurrence, Colon surgery, Internal medicine, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Young adult, education, Colectomy, ComputingMilieux_MISCELLANEOUS, Crohn's disease, education.field_of_study, Microscopy, Confocal, medicine.diagnostic_test, business.industry, Middle Aged, Prognosis, medicine.disease, Endoscopy, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Confocal laser endomicroscopy (CLE) has been shown to predict relapse in inflammatory bowel disease, but its value in the detection of postoperative recurrence in Crohn's disease (CD) is unknown. The aims of this pilot study performed in patients with CD after ileocolonic resection were to compare the macroscopic appearance of the neoterminal ileum, according to the endoscopic Rutgeerts score, with the microscopic findings provided by CLE 6 to 12 months after surgery and to assess the predictive values of CLE-generated parameters for predicting further recurrence in patients with postoperative endoscopic remission.In 25 consecutive patients with CD within 6 to 12 months of surgery, the neoterminal ileum was examined by standard white-light endoscopy (Rutgeerts scale) followed by CLE (Watson grade). Only patients without endoscopic recurrence (Rutgeerts i0 and i1) were then followed endoscopically and clinically (median follow-up 38 months).At the time of the first postoperative colonoscopy, 18 patients (72%) were in endoscopic remission, and 7 (28%) experienced an endoscopic recurrence (Rutgeerts ≥i2). The Rutgeerts score was significantly correlated with the Watson score (ρ = 0 .73; P .0001). The Watson scores at baseline were significantly higher in patients with further endoscopic recurrence (median 2.0; interquartile range [IQR] 1.5-2.0) than in those with endoscopic remission (median 1.0; IQR 1.0-1.0; P = .032) and were significantly higher in patients with clinical relapse (medium 2.0, IQR 2.0-2.0) compared with those in clinical remission (median 1.0; IQR 1.0-1.0; P = .036).CLE could be useful in monitoring patients with CD after intestinal resection. Further studies with a larger population are necessary to confirm these preliminary results.
Published: 2019

18. Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study

Author: Vered Abitbol, Stephanie Viennot, Catherine Reenaers, Jean-Marie Reimund, Lucine Vuitton, Mélanie Serrero, Philippe Seksik, Jérôme Filippi, Mathurin Fumery, Guillaume Savoye, David Laharie, Bénédicte Caron, Caroline Trang-Poisson, Jean-Pierre Bronowicki, Guillaume Bouguen, Benjamin Pariente, Maud Reymond, Laurent Peyrin-Biroulet, Stéphane Nancey, Romain Altwegg, L Caillo, Franck Carbonnel, Yoram Bouhnik, Aurelien Amiot, Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Université de Montpellier (UM)-CHU Saint-Eloi, Université de Liège, Hôpital Nord [CHU - APHM], Institut des maladies de l'appareil digestif [Nantes] (IMAD), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépato-gastroentérologie, Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Gastro-entérologie et hépatologie [AP-HP Hôpital Cochin], Sorbonne Paris Cité-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), douville, sabine, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Liège (CHU-Liège), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Service d'Hépatologie et de Gastroentérologie [Lyon], Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Chimie Moléculaire de Paris Centre (FR 2769), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Paris Cité-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Department of Hepato-Gastroenterology, University Hospital Estaing of Clermont-Ferrand, Université d'Auvergne (Clermont Ferrand 1) (UdA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Fédération de Médecine Translationelle de Strasbourg (FMTS)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Université d'Auvergne - Clermont-Ferrand I (UdA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Adult, Male, Crohn’s disease, vedolizumab, medicine.medical_specialty, Adolescent, Cholangitis, Sclerosing, Population, Antibodies, Monoclonal, Humanized, Malignancy, Gastroenterology, Inflammatory bowel disease, Primary sclerosing cholangitis, Vedolizumab, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, inflammatory bowel disease, Internal medicine, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, ulcerative colitis, education.field_of_study, Crohn's disease, business.industry, primary sclerosing cholangitis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, General Medicine, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract: Background Whether vedolizumab may be effective as a treatment for primary sclerosing cholangitis [PSC] in patients with inflammatory bowel disease [IBD] remains controversial. Methods We performed a retrospective observational study of consecutive patients with IBD and PSC, treated with vedolizumab for at least 30 weeks in 22 centres of GETAID from January 2015 to June 2016. The outcomes included a decrease in the serum alkaline phosphatase [ALP] concentration of at least 50% from baseline to Week 30 or 54, a change in any serum liver enzymes concentrations, and an assessment of the efficacy and safety of vedolizumab in IBD. Results Among 75 patients with active IBD and PSC treated with vedolizumab, 21 patients discontinued vedolizumab before Week 30 [due to lack of efficacy in 19 and malignancy in two patients]. In the remaining 54 patients, a decrease in the serum ALP concentration of at least 50% from baseline to Weeks 30 and 54 was observed in four [7%] and four [11%] patients, respectively. No significant change was observed in serum liver enzyme concentrations at week 30 or 54. After a median follow-up period of 19.4 [14.0–29.9] months, nine cases of digestive neoplasia [colorectal neoplasia in seven and cholangiocarcinoma in two] were reported. Conclusions In patients with IBD and PSC, vedolizumab did not improve serum liver enzyme concentrations at week 30 or 54. Nine cases of digestive cancer occurred during the follow-up period, confirming the need for a tight surveillance programme in this population.
Published: 2019

19. Comparison of short- and long-term effectiveness between ustekinumab and vedolizumab in patients with Crohn's disease refractory to anti-tumour necrosis factor therapy

Author: Luc Manlay, Gilles Boschetti, Bruno Pereira, Bernard Flourié, Michel Dapoigny, Maud Reymond, Elisa Sollelis, Claire Gay, Mathilde Boube, Anthony Buisson, Stéphane Nancey, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'Hépatogastroentérologie [CHU Lyon-Sud], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Molé, Christine, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Antibodies, Monoclonal, Humanized, Gastroenterology, Vedolizumab, MESH: Ustekinumab* / therapeutic use, 03 medical and health sciences, 0302 clinical medicine, Refractory, Crohn Disease, Internal medicine, Ustekinumab, medicine, Clinical endpoint, Humans, Pharmacology (medical), 030212 general & internal medicine, MESH: Treatment Outcome, Crohn's disease, Hepatology, business.industry, MESH: Antibodies, Monoclonal, Humanized / therapeutic use, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bowel resection, Odds ratio, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Treatment Outcome, MESH: Crohn Disease* / drug therapy, Monoclonal, 030211 gastroenterology & hepatology, MESH: Tumor Necrosis Factor Inhibitors, Tumor Necrosis Factor Inhibitors, business, medicine.drug
Abstract: International audience; Background The best option between vedolizumab and ustekinumab after anti-tumour necrosis factor (TNF) failure remains unclear in Crohn's disease.Aims To compare the short- and long-term effectiveness of vedolizumab and ustekinumab in Crohn's disease patients with prior anti-TNF exposure.Methods All Crohn's disease patients treated with ustekinumab or vedolizumab after exposure to at least one anti-TNF agent were included from two referral centres. Primary endpoint was corticosteroid-free clinical remission defined as Crohn's disease activity index 35 years old (OR = 0.41 [0.19-0.87]), with noncomplicated phenotype (OR=0.42 [0.18-0.96]), no prior bowel resection (OR = 0.49 [0.24-0.96]), and no steroids at baseline (OR=0.47 [0.23-0.97]).Conclusion Ustekinumab was more effective to achieve early and long-term effectiveness than vedolizumab in Crohn's disease patients who previously failed response to anti-TNF agents.
Published: 2021

20. effectiveness of third-class biologic treatment in crohn’s disease: a multi-center retrospective cohort study

Author: C. M. Alves, Henit Yanai, Morine Fibelman, Claire Liefferinckx, Marina Coletta, Hadar Amir-Barak, Johan Burisch, Afroditi Mpitouli, Manuel Barreiro-de Acosta, Mohamed Attauabi, Triana Lobaton, Mariann Rutka, Joshua Taylor, Konstantinos Karmiris, Javier P. Gisbert, Carla Marinelli, Kalliopi Foteinogiannopoulou, Daniela Pugliese, Edoardo Savarino, Borja Otero-Alvarin, V Domislović, Ariella Bar-Gil Shitrit, Alessandro Armuzzi, Zeljko Krznaric, Carl Eriksson, Mohamed Korani, Waqqas Afif, Jimmy K. Limdi, Nitsan Maharshak, Davide Giuseppe Ribaldone, A Cremer, G Suris, Tamás Molnár, Stéphane Nancey, Ioannis E. Koutroubakis, Jakob Benedict Seidelin, Caroline di Jiang, Uri Kopylov, Tim Raine, Pauliina Molander, Katja Tepes, Ahmad Albshesh, David Drobne, María Chaparro, Marie Truyens, Fernando Magro, Albshesh, Ahmad [0000-0001-8962-4263], Ribaldone, Davide G. [0000-0002-9421-3087], Barreiro-de Acosta, Manuel [0000-0001-5915-1477], Eriksson, Carl [0000-0002-1046-383X], Foteinogiannopoulou, Kalliopi [0000-0003-0554-5256], Gisbert, Javier P. [0000-0003-2090-3445], Attauabi, Mohamed [0000-0003-0323-7030], Afif, Waqqas [0000-0001-6869-0982], Lobaton, Triana [0000-0003-1817-7704], Krznaric, Zeljko [0000-0003-3758-4540], Chaparro, Maria [0000-0002-9275-4242], Burisch, Johan [0000-0002-3312-5139], Apollo - University of Cambridge Repository, Ribaldone, Davide G [0000-0002-9421-3087], Gisbert, Javier P [0000-0003-2090-3445], HUS Abdominal Center, Gastroenterologian yksikkö, and Department of Medicine
Subjects: vedolizumab, Crohn’s disease, medicine.medical_specialty, anti-TNF failure, treatment failure, treatment response, ustekinumab, Biologic treatment, Inflammatory bowel diseases, Treatment response, Article, Group B, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, Malaltia de Crohn, Internal medicine, Anti-TNF failure, Ustekinumab, medicine, Medicine and Health Sciences, In patient, Crohn's disease, business.industry, Retrospective cohort study, General Medicine, medicine.disease, 3. Good health, Malalties inflamatòries intestinals, Treatment failure, 3121 General medicine, internal medicine and other clinical medicine, 030220 oncology & carcinogenesis, Medicine, 030211 gastroenterology & hepatology, business, Cohort study, medicine.drug
Abstract: Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti- Tumor necrosis factors (TNFs), however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included, 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A), the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9), 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52, 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9), 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.
Published: 2021

21. Low Levels of Fecal Calprotectin 3 Months After Surgery Predict Subsequent Endoscopic Postoperative Remission in Crohn's Disease

Author: Florian Veyre, Gilles Boschetti, Camille Meunier, Charlotte Cuerq, Claire Gay, Anne-Laure Charlois, Remi Duclaux-Loras, Pauline Danion, Eddy Cotte, Vahan Kepenekian, Anne Mialon, Mathias Faure, Xavier Roblin, Bernard Flourie, Stéphane Nancey, Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and CarMeN, laboratoire
Subjects: Adult, Male, Crohn’s disease, medicine.medical_specialty, Adolescent, Physiology, [SDV]Life Sciences [q-bio], Postoperative recurrence, Resection, Feces, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Fecal calprotectin, Crohn Disease, Internal medicine, Positive predicative value, medicine, Humans, In patient, Colectomy, Aged, Crohn's disease, Receiver operating characteristic, business.industry, Remission Induction, Gastroenterology, Middle Aged, Hepatology, medicine.disease, Surgery, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Calprotectin, business, Crp, Leukocyte L1 Antigen Complex, Biomarkers, Follow-Up Studies
Abstract: International audience; BACKGROUND/AIMS: In Crohn's disease (CD) few data are available on the usefulness of monitoring fecal calprotectin (FC) in the early postoperative setting. We assessed prospectively the accuracy of FC measured 3 months after surgery to predict the risk of endoscopic postoperative recurrence (POR) within 1 year after resection. METHODS: In 55 consecutive CD patients who had undergone ileocolonic resection samples were collected 3 months after surgery for measuring serum CRP and FC. Endoscopic POR was assessed by ileocolonoscopy within 6-12 months (median 7 months). Receiver operating characteristic (ROC) curves were generated to assess accuracy of the markers, to determine the best threshold and to calculate sensitivity, specificity, positive and negative predictive values. RESULTS: In contrast with median CRP levels, median FC concentrations measured 3 months after surgery were significantly higher in patients who later experienced endoscopic POR (Rutgeerts ≥ i2) compared with those who stayed in endoscopic remission within the following 6-12 months (205 μg/g IQR [106-721] vs. 103 μg/g IQR [60-219], p = 0.008). Area under the ROC curve for FC was 0.71. The best cutoff value of FC to identify patients in subsequent endoscopic remission 3 months after surgery was 65 μg/g (96% sensitivity, 31% specificity, 50% positive and 91% negative predictive values). In multivariate analysis, FC \textless 65 µg/g at 3 months was the only factor associated with subsequent endoscopic remission. CONCLUSION: FC measured 3 months after surgery below 65 μg/g is an accurate marker to identify CD patients who will later stay in endoscopic remission within 1 year after resection.
Published: 2021

22. P047 The ATG16L1 T300A polymorphism in Crohn’s Disease patients leads to abnormal autophagy flux in dendritic cells

Author: Aurore Rozières, Gilles Boschetti, Christophe Viret, O Dinet, G Quiniou, O Cervantes, Stéphane Nancey, Mathias Faure, and M Verdet
Subjects: Crohn's disease, business.industry, Autophagy, Gastroenterology, General Medicine, medicine.disease, Inflammatory bowel disease, Immune system, Polymorphism (computer science), medicine, Cancer research, Antigen-presenting cell, business, Flux (metabolism), ATG16L1
Abstract: Background Crohn’s disease is a chronic inflammatory bowel disease, whose pathogenesis is largely determined by an inappropriate immune response towards luminal microbiota in genetically susceptible hosts, affecting in particular genes involved in the autophagy process. The autophagy-related ATG16L1 T300A variant is one of the most frequently associated polymorphisms with susceptibility to Crohn’s disease, but the functional consequences of this polymorphism on the dynamic properties of the autophagy flux remains unknown. Methods Using dynamic monitoring of LC3 lipidation, a key protein marker of autophagy, we have quantitatively analysed the autophagic flux of human primary dendritic cells, which are very potent antigen-presenting cells whose function is critical in Crohn’s disease. Results The detailed analysis of the dynamic properties of the autophagic flux reveal that the maturation process in dendritic cells from healthy subjects is associated with a decrease of the velocity and the intensity on the autophagy flux although the turnover of autophagosome formation was maintained, demonstrating the capacity of resilience of the autophagy flux for a maintenance of functional autophagy during maturation process. Strikingly, the expression of the ATG16L1 T300A variant, but not NOD2 R702W variant, in dendritic cells from patients with Crohn’s disease is associated with a disorder of the autophagic flux dynamics in immature dendritic cells, that was not modulated upon maturation. The lack of adaptation of the autophagy flux in ATG16L1 T300A expressing dendritic cells of Crohn’s disease patients, during their maturation was not associated with altered phenotypic acquisition of maturation markers but highlighted a very specific autophagic flux signature. Conclusion Dendritic cells of Crohn’s patients expressing the autophagy-related ATG16L1 T300A have an altered autophagy flux, that could affect their function and contribute to the pathogenesis of Crohn’s disease.
Published: 2021

23. P289 A French nationwide prospective study on patients with Crohn’s disease and ulcerative colitis treated with Infliximab-biosimilar CT-P13 in a real-life setting: two-year follow-up of the ReFLECT study

Author: N Mammar, D. Laharie, M Assing, Stéphane Nancey, and Y. Bouhnik
Subjects: Pediatrics, medicine.medical_specialty, Crohn's disease, business.industry, Gastroenterology, Biosimilar, General Medicine, medicine.disease, Ulcerative colitis, Infliximab, Biosimilar Pharmaceuticals, Delayed hypersensitivity, medicine, business, Prospective cohort study, Adverse effect, medicine.drug
Abstract: Background ReFLECT study was carried out to investigate real-life use of CT-P13, the first monoclonal antibody biosimilar to infliximab (IFX) originator. Methods This multicentre, prospective, observational study was conducted in France to assess characteristics of patients (pts) receiving CT-P13, its effectiveness and safety in a real-life setting. Eligible were both pts who had been switched from IFX originator (IFXS) and IFX-naïve pts started on CT-P13 (IFXN). These interim descriptive statistical analyses are about pts with Crohn’s disease (CD) and ulcerative colitis (UC). Results Among the 1370 adult pts included between October 2016 and April 2019, data were analysed for 508 CD pts (48.6% males; mean age ± SD: 37.7±13.7; median [Q1;Q3] disease duration: 6.2 [1.9;13.7] years; 323 IFXN/145 IFXS) and 213 UC pts (54%; 42.9±17.2; 5.4 [1.6;12.8]; 154 IFXN/46 IFXS). Previous biologics other than IFX were taken by 32.9% of CD and 39.0% of UC pts; 31% (CDS) and 23% (UCS) of pts were switched from IFX originator to CT-P13. At the time of the first administration of CT-P13, disease had been more active in IFXN vs IFXS pts: 52.9% vs 13.3% in CD with a median [Q1;Q3] Harvey Bradshaw Index (HBI) of 4 [1;8] vs 1 [0;2] and, 82.9% vs 33.3% in UC with a median Mayo Score of 7 [3;10] vs 2 [0;4]. In IFXS pts, disease activity remained stable after 2 years of treatment with median differences of HBI and Mayo score since first administration of 1 [0;2] and 0 [-4;1]. In IFXN pts, median differences of HBI and Mayo score since first administration were -2 [-7;1] and -7 [-8;-5]; CT-P13 brought disease activity down to levels below or comparable to those seen in IFXS pts. Reasons for CT-P13 withdrawing and safety data are reported in Tables 1 and 2. Conclusion Year 2 follow-up data indicate that CT-P13 effectively induced improvement in disease activity in IFXN pts with CD or UC and maintained stable activity in IFXS pts. This real-life study did not highlight any new safety concerns.
Published: 2021

24. Variation of faecal calprotectin level within the first three months after bowel resection is predictive of endoscopic postoperative recurrence in Crohn's disease

Author: Xavier Hébuterne, Mathurin Fumery, Stéphane Nancey, Mathilde Boube, Benjamin Pariente, Laurent Peyrin-Biroulet, Anthony Buisson, Xavier Roblin, Bruno Pereira, Gilles Bommelaer, David Laharie, Régine Minet-Quinard, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU St Etienne, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Clermont-Ferrand, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, PHRC inter-regional Association Francois Aupetit 3i Nature CHU Clermont-Ferrand, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Male, Time Factors, medicine.medical_treatment, Azathioprine, Gastroenterology, Severity of Illness Index, law.invention, Feces, 0302 clinical medicine, Randomized controlled trial, Crohn Disease, law, Recurrence, Medicine, Postoperative Period, Colectomy, ComputingMilieux_MISCELLANEOUS, Crohn's disease, Anti-Inflammatory Agents, Non-Steroidal, Remission Induction, Bowel resection, Middle Aged, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Curcumin, Placebo, 03 medical and health sciences, Young Adult, Predictive Value of Tests, Internal medicine, Humans, In patient, Hepatology, business.industry, Significant difference, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Faecal calprotectin, ROC Curve, business, Leukocyte L1 Antigen Complex, Biomarkers
Abstract: Background Early prediction of postoperative recurrence (POR) remains a major concern in Crohn's disease (CD). Aims To assess serial faecal calprotectin (Fcal) monitoring within the first three months to predict CD endoscopic POR. Methods In a multicenter randomized controlled trial, CD patients received azathioprine 2.5 mg/kg/day with oral curcumin (3 g/day) or placebo. Fcal was measured at baseline, one month (M1) and M3. Endoscopic POR at M6 was defined as Rutgeerts’ index ≥ i2b (central reading). Results Among the 48 patients included, there was no significant difference of median Fcal levels at baseline (p = 0.15), M1 (p = 0.44) and M3 (p = 0.28) between patients with or without endoscopic POR at M6. Fcal kinetics during the first 3 months after surgery was significantly different between the patients with or without POR at M6 (p = 0.021). The median variation between Fcal level at baseline and M3 (ΔFcal M3–M0) was significantly higher in patients with endoscopic POR compared to those without POR (p = 0.01). ΔFcal M3–M0 >+10% demonstrated the best performances to predict endoscopic POR at M6 (AUC=0.73, sensitivity=64.7%[41.1–82.7], specificity=87.5%[68.0–96.3], negative predictive value=77.8%[57.5–91.4] and positive predictive value=78.6%[49.2–95.3]). Conclusion Fcal variation within the first three months after ileocolonic resection is a promising predictor of early endoscopic POR in CD patients.
Published: 2020

25. Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease

Author: Philippe Seksik, Xavier Treton, Mathurin Fumery, Claire Auzolle, Nicolas Barnich, Lionel Le Bourhis, Benjamin Pariente, Anthony Buisson, Loic Brot, Stéphane Nancey, Harry Sokol, Carmen Stefanescu, Matthieu Allez, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Clermont-Ferrand, CHU Amiens-Picardie, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, This study has been supported by grants from MSD France, Association Francois Aupetit, the Helmsley Charitable Trust and Inserm., Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AgroParisTech, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Universitaire Clermont Ferrand, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Autophagie infections immunité – Autophagy Infection Immunity, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Adult, Male, medicine.medical_specialty, Firmicutes, Disease, Gut flora, Gastroenterology, digestive system, Endoscopy, Gastrointestinal, Ileal resection, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Crohn Disease, Ileum, Recurrence, Risk Factors, Internal medicine, Proteobacteria, medicine, microbiota, Humans, Postoperative Period, Prospective Studies, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Crohn's disease, biology, business.industry, Lachnospiraceae, Healthy subjects, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, mucosa-associated, Middle Aged, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Gastrointestinal Microbiome, Cohort, 030211 gastroenterology & hepatology, Female, business, Ileal mucosa
Abstract: ObjectiveFollowing ileal resection for Crohn’s disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence.Patients and methodsIleal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France.ResultsIleal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors.ConclusionSurgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.
Published: 2020

26. Postoperative Endoscopic Recurrence on the Neoterminal Ileum But Not on the Anastomosis Is Mainly Driving Long-Term Outcomes in Crohn's Disease

Author: Madeleine Bezault, Philippe Seksik, Mathurin Fumery, Nassim Hammoudi, Benjamin Pariente, Anthony Buisson, Stéphane Nancey, Claire Auzolle, Lionel Le Bourhis, Gilles Boschetti, My-Linh Tran Minh, Xavier Treton, Matthieu Allez, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Crohn's disease, medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, Gold standard, Gastroenterology, Ileum, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Anastomosis, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Endoscopy, Surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Interquartile range, 030220 oncology & carcinogenesis, medicine, Long term outcomes, 030211 gastroenterology & hepatology, In patient, business, ComputingMilieux_MISCELLANEOUS
Abstract: Early ileocolonoscopy within the first year after surgery is the gold standard to evaluate recurrence after ileocolonic resection for Crohn's disease (CD). The aim of the study was to evaluate the association between the presence and severity of anastomotic and ileal lesions at early postoperative ileocolonoscopy and long-term outcomes. The REMIND group conducted a prospective multicenter study. Patients operated for ileal or ileocolonic CD were included. An ileocolonoscopy was performed 6 months after surgery. An endoscopic score describing separately the anastomotic and ileal lesions was built. Clinical relapse was defined by the CD-related symptoms, confirmed by imaging, endoscopy or therapeutic intensification; CD-related complications; or subsequent surgery. Among 225 included patients, long-term follow-up was available in 193 (median follow-up: 3.82 years [interquartile range: 2.56-5.41]). Median clinical recurrence-free survival was 47.6 months. Clinical recurrence-free survival was significantly shorter in patients with ileal lesions at early postoperative endoscopy whatever their severity was (I(1) or I(2,3,4)) as compared to patients without ileal lesions (I(0)) (I(0) vs I(2,3,4): P = 0.0003; I(0) vs I(1): P = 0.0008 and I(1) vs I(2,3,4): P = 0.43). Patients with exclusively ileal lesions (A(0)I(1,2,3,4)) had poorer clinical long-term outcomes than patients with exclusively anastomotic lesions (A(1,2,3)I(0)) (P = 0.009). A score describing separately the anastomotic and ileal lesions might be more appropriate to define postoperative endoscopic recurrence. Our data suggest that patients with ileal lesions, including mild ones (I(1)), could beneficiate from treatment step-up to improve long-term outcomes.
Published: 2020

27. T cell clonal expansions in ileal Crohn’s disease are associated with smoking behaviour and postoperative recurrence

Author: Benjamin Pariente, Azucena Salas, Xavier Treton, Matthieu Allez, Stéphane Nancey, Victor Chardiny, Anthony Buisson, Mathurin Fumery, Harry Sokol, Nicolas Barnich, Marjolaine Ngollo, Hugo Bottois, Carmen Stefanescu, Philippe Seksik, Ana Maria Corraliza, Claire Auzolle, Lionel Le Bourhis, Kevin Perez, Service d'hépato-gastro-entérologie, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Helmsley Charitable Trust Association Francois Aupetit MSD France laboratories, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA)
Subjects: Adult, Male, medicine.medical_specialty, Microarray, T cell, Receptors, Antigen, T-Cell, Gastroenterology, Cohort Studies, Pathogenesis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Recurrence, Internal medicine, medicine, Humans, Cytotoxic T cell, Postoperative Period, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Crohn's disease, medicine.diagnostic_test, business.industry, Smoking, T-cell receptor, Area under the curve, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Ileitis, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Endoscopy, Treatment Outcome, medicine.anatomical_structure, Female, 030211 gastroenterology & hepatology, business
Abstract: T cell clonal expansions are present in the inflamed mucosa of patients with Crohn’s disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection.MethodsT cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively.ResultsTCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment.ConclusionClonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven.Trial registration numberNCT03458195.
Published: 2019

28. Concentrations of Ustekinumab During Induction Therapy Associate With Remission in Patients With Crohn’s Disease

Author: Anne Mialon, Ninon Soufflet, Stéphane Paul, Stéphane Nancey, Remi Duclaux-Loras, Charlotte Cuercq, Nicolas Williet, Anne-Laure Charlois, Gilles Boschetti, Pauline Danion, Xavier Roblin, Bernard Flourié, Mathias Faure, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Laboratoire de Biochimie et Toxicologie [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CCSD, Accord Elsevier, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Disease, Sensitivity and Specificity, 03 medical and health sciences, Feces, 0302 clinical medicine, Crohn Disease, Gastrointestinal Agents, Interquartile range, Predictive Value of Tests, Internal medicine, Ustekinumab, medicine, Humans, Prospective Studies, Prospective cohort study, Crohn's disease, Hepatology, biology, medicine.diagnostic_test, business.industry, C-reactive protein, Remission Induction, Gastroenterology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], C-Reactive Protein, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, biology.protein, Trough level, 030211 gastroenterology & hepatology, business, Leukocyte L1 Antigen Complex, Biomarkers, medicine.drug
Abstract: International audience; Ustekinumab is approved for treatment of Crohn's disease (CD).1,2 Few data are available to assess the usefulness of monitoring inflammatory biomarkers and therapeutic drug monitoring to predict response to ustekinumab. We conducted a prospective study to assess the relationships between these parameters and the clinical outcome at week 16 in active CD patients receiving ustekinumab.
Published: 2019

29. 26 COMPARISON OF SHORT AND LONG-TERM EFFICACY BETWEEN USTEKINUMAB AND VEDOLIZUMAB IN PATIENTS WITH CROHN'S DISEASE REFRACTORY TO ANTI-TNF THERAPY

Author: Stéphane Nancey, Anthony Buisson, Luc Manlay, Bruno Pereira, and Gilles Boschetti
Subjects: medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Gastroenterology, medicine.disease, Vedolizumab, Refractory, Internal medicine, Ustekinumab, Medicine, In patient, Anti-TNF therapy, business, medicine.drug
Published: 2021

30. 457 ADALIMUMAB FOR PATIENTS WITH CROHN'S DISEASE COMPLICATED BY INTRA-ABDOMINAL ABSCESS : LONG-TERM RESULTS OF THE MICA STUDY

Author: Vered Abitbol, Nina Dib, Benjamin Pariente, Yoram Bouhnik, Stephanie Viennot, Xavier Roblin, Laurent Peyrin-Biroulet, Kristell Desseaux, Medina Boualit, Maria Nachury, Lucine Vuitton, Anthony Buisson, Jérôme Filippi, Guillaume Pineton de Chambrun, Carmen Stefanescu, Alexandre Aubourg, Jacques Moreau, Stéphane Nancey, Romain Altwegg, Magaly Zappa, Mélanie Serrero, Philippe Seksik, Jérôme Lambert, Arnaud Bourreille, Georgia Malamut, and Aurelien Amiot
Subjects: medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Gastroenterology, medicine, Adalimumab, Intra-abdominal Abscess, Long term results, business, medicine.disease, Surgery, medicine.drug
Published: 2021

31. Fetal death in utero and miscarriage in a patient with Crohn’s disease under therapy with ustekinumab: case-report and review of the literature

Author: P Danion, Mathieu Uzzan, Stéphane Nancey, Gilles Boschetti, M. Chauvenet, C. Bergoin, Bernard Flourié, Xavier Roblin, C. Venturin, Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Adult, Crohn’s disease, medicine.medical_specialty, Case Report, Disease, Miscarriage, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Pharmacotherapy, Crohn Disease, Gastrointestinal Agents, Pregnancy, Psoriasis, Internal medicine, Ustekinumab, medicine, Humans, lcsh:RC799-869, Fetal Death, ComputingMilieux_MISCELLANEOUS, Crohn's disease, business.industry, Gastroenterology, General Medicine, Anti-IL12/23, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Abortion, Spontaneous, 030220 oncology & carcinogenesis, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, 030211 gastroenterology & hepatology, lcsh:Diseases of the digestive system. Gastroenterology, business, medicine.drug
Abstract: Background Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn’s disease (CD). Case presentation We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage. Conclusion Ustekinumab is a relatively new pharmacotherapy and in addition to this clinical case, we reviewed the published literature concerning the use of this treatment during pregnancy and its consequences on pregnancy and fetus outcome.
Published: 2017

32. P131 The simplified MARIA score is strongly correlated with the MARIA and Clermont scores to analyse the luminal activity of Crohn’s disease (CD) in magnetic resonance and is easier to calculate

Author: Stéphane Paul, S Jardin, Gilles Boschetti, Bernard Flourié, Xavier Roblin, Pauline Veyrard, Anne-Emmanuelle Berger, Stéphane Nancey, and M cuilleron
Subjects: medicine.medical_specialty, Leukocyte L1 Antigen Complex, Crohn's disease, medicine.diagnostic_test, business.industry, Gastroenterology, Magnetic resonance imaging, Ileum, General Medicine, medicine.disease, medicine.anatomical_structure, Internal medicine, Edema, Disease remission, medicine, Phenobarbital, medicine.symptom, business, medicine.drug
Abstract: Background Two scores have shown their interest in evaluating the luminal activity of CD in magnetic resonance (MR), the MARIA and Clermont scores, but their calculation can be complicated in clinical practice. Recently, the Spanish authors validated a new simplified MARIA score (MARIAs) and retrospectively showed a very good correlation with the initial MARIA score (1). The purpose of this study was to validate this correlation in an independent cohort and to compare its feasibility with other scores. Methods This was a retrospective analysis of all MR performed in our department to evaluate the luminal activity of CD. Two independent radiologists each calculated the MARIA, Clermont and MARIAs scores (wall thickness > 3mm, oedema, comb sign, ulcerations), each blind to the other and blind to clinical activity. In case of disagreement between the two radiologists, a third reader analyzed MR activity. Correlations were calculated between these three tests for the entire cohort. In addition, concordance tests were performed for predetermined thresholds of 7 to 11 for the MARIA score, 8.5 to 12.5 for the Clermont score and 1 to 2 for the MARIAs score. The duration of the analysis was reported for each reading. Isolated colonic CD were excluded from the study. Results One hundred and twenty-one CD were included (65 in clinical and biological activity, 33% ileal phenotype, mean age: 38.5 years, sex ratio M/F = 54.5%). The agreement between the MARIA score between 7 and 11, the Clermont score between 8.5 and 12.5 and the MARIAs score between 1 and 2 was 0.92 (Fleiss kappa test). The correlation between the MARIA score and its simplified score was very strong (r = 0.93; 95% CI: 0.9–0.95) as well as between the Clermont score and the MARIAs score (r = 0.92 95% CI: 0.89–0.95). Inter-observer agreement was significantly higher in the calculation of the MARIAs score (96%) compared with 80% for the MARIA and Clermont scores (p = 0.04). Reading time was significantly faster for the MARIAs score (3.45 ± 0.4 min) compared with the MARIA (10.05 ± 1.2 min) and Clermont (13.5 ± −3.5 min) scores (p < 0.01). Positive predictive values for deep remission (clinical remission and calprotectin < 250 µg/g stool) were 95% at thresholds Conclusion In this independent cohort, we confirm the very strong correlation between the simplified MARIA score and the two reference scores (MARIA and Clermont) in the analysis of MC luminal activity as well as its rapid calculation and strong inter-observer agreement.
Published: 2020

33. OP04 Long-term outcomes after ileocolonic resection in Crohn’s disease according to the severity of early endoscopic recurrence

Author: M L Tran Minh, Claire Auzolle, Lionel Le Bourhis, Benjamin Pariente, Xavier Treton, P. Seksik, Mathurin Fumery, A Buisson, Stéphane Nancey, Nassim Hammoudi, Gilles Boschetti, Madeleine Bezault, and Mathieu Allez
Subjects: medicine.medical_specialty, Crohn's disease, medicine.diagnostic_test, business.industry, Gastroenterology, General Medicine, Gold standard (test), medicine.disease, Surgery, Endoscopy, Resection, Long term outcomes, Medicine, business
Abstract: Background Early ileocolonoscopy within the first year after surgery is the gold standard to evaluate post-operative recurrence after ileocolonic resection for Crohn’s disease (CD). The aim of the study was to evaluate the association between lesions at ileocolonoscopy 6 months after surgery and long-term outcomes. Methods The REMIND group conducted a prospective multicentre study. Patients operated for ileal or ileocolonic CD were included. An ileocolonoscopy was performed 6 months after surgery. An endoscopic classification separating anastomotic and ileal lesions was built (Ax for anastomotic lesions; Ix for neo-terminal ileum lesions evaluated according to the Rutggerts score). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy or therapeutic intensification, CD-related complication or subsequent surgery. Results A total of 225 patients were included. Long-term data were available for 193 patients (86%). Median follow-up was 3.82 years (IQR:2.56–5.41) from surgery. Median clinical recurrence-free survival was 47.6 months. Clinical recurrence-free survival was significantly shorter in patients with ileal lesions at early post-operative endoscopy whatever their severity (I1 or I2I3I4) compared with patients without (I0) (median survivals: 68.5, 33.0 and 39.1 months, respectively, for I0, I1 and I2I3I4; I0 vs. I2I3I4: p = 0.0003; I0 vs. I1: p = 0.0008 and I1 vs. I2I3I4: p = 0.43). Patients with at least semi-circumferential anastomotic ulcerations (A2 or A3) had more anastomotic occlusive manifestations than patients without (A0 or A1) (A0 vs. A2A3: p = 0.01; A0 vs. A1: p = 0.83; A1 vs. A2A3: p = 0.05). Conclusion A classification separating anastomotic and ileal lesions might be more appropriate to define post-operative endoscopic recurrence. Patients with ileal lesions, including mild ones (I1), could beneficiate from treatment step up to improve long-term outcome.
Published: 2020

34. DOP06 Non-invasive identification of adherent-invasive E. coli in patients with Crohn’s disease

Author: Stéphane Nancey, Stéphanie Rodriguez, Nicolas Barnich, Xavier Hébuterne, N Ballet, Emilie Vazeille, Mathieu Allez, Bruno Pereira, Elisabeth Billard, Mathurin Fumery, P. Seksik, A Buisson, L Peyrin-Biroulet, and Benjamin Pariente
Subjects: medicine.medical_specialty, Crohn's disease, medicine.diagnostic_test, business.industry, Non invasive, Gastroenterology, Mucous membrane, General Medicine, medicine.disease, medicine.anatomical_structure, Internal medicine, Biopsy, medicine, Microbial colonization, In patient, business
Abstract: Background Medications limiting the adhesion of ‘adherent and invasive E. coli’ (AIEC) represent potential strategies to treat Crohn’s disease (CD). However, the ileal AIEC identification is a time-consuming procedure, and the number of AIEC strains which colonise ileal CD mucosa remains unknown. There is an unmet need for non-invasive biomarkers to identify patients colonised by AIEC. We aimed to evaluate non-invasive biomarker of ileal AIEC colonisation in patients with CD. Methods This prospective and multi-centre study included CD patients requiring ileocoloscopy. Saliva, serum, stools and ileal biopsies were collected. Abundance and global invasive ability of ileal or faecal E. coli were performed. Isolated E. coli were characterised as AIEC or non-AIEC on I407 epithelial cells and THP1 macrophages. The ERIC-PCR profiles of ileal E. coli were performed. Ileal E. coli/CEACAM6 interaction was analysed by a yeast aggregation test and T84 assays (CEACAM6 protein expression, adhesion inhibition test with D-mannose). Quantification of serum anti-E. coli and ileal or salivary CEACAM6 was realised by ELISA. Results Overall, 102 CD patients were enrolled in this study and 25.8% of them exhibited ileal AIEC colonisation (AIEC+). The abundance and global invasive ability of ileal mucosa-associated E. coli were higher in AIEC+ CD patients compared with CD patients without AIEC (AIEC−) (p = 0.0065 and p = 0.0007, respectively). There was no difference between faecal abundance and invasive ability of E. coli between AIEC+ and AIEC− patients. The ERIC-PCR profiles of ileal E. coli showed that CD AIEC+ were for 78% of them colonised by not more than 2 clonal AIEC strains. In addition, AIEC were able to interact with CEACAM6 by binding D-mannose residues and to induce CEACAM6 expression in T84 cells (p = 0.0009 and p = 0.0185, vs. non-AIEC; respectively). This was also supported by adhesion inhibition test. Serum anti-E. coli level was higher for CD AIEC+ (vs. CD AIEC-). Ileal CEACAM6 level were positively correlated with abundance of ileal associated E. coli in AIEC+ patients (r = 0.4000; p = 0.0362) and with salivary CEACAM6 level (r = 0.4690; p < 0.0001). The non-invasive biomarker ‘serum anti-E.coli/salivary CEACAM6’ index was higher for CD AIEC+ (p = 0.0174; vs. CD AIEC-). A cut-off value < 1.34 × 10−6 eliminated the presence of ileal AIEC with a high negative predictive value (90% CI95% [69%–95%]). Conclusion Our study reported that identification of faecal AIEC cannot replace identification of AIEC from ileal biopsies, most of AIEC infection are mono or bi-clonal (≤ 2 strains) and that non-invasive biomarker such as ‘serum anti-E.coli/salivary CEACAM6’ index could be helpful to screen CD patients for AIEC infection.
Published: 2020

35. P136 Faecal calprotectin as therapeutic target in patients with Crohn’s disease treated with anti-TNF: a meta-analysis of individual data

Author: Pauliina Molander, A Buisson, A Mami, I Nogueira, Gilles Boschetti, Daniela Pugliese, Stéphane Nancey, and Bruno Pereira
Subjects: medicine.medical_specialty, Crohn's disease, business.industry, Gastroenterology, General Medicine, medicine.disease, Faecal calprotectin, Crohn's Disease Activity Index, Inflammatory bowel disease, Infliximab, 3. Good health, Internal medicine, medicine, Adalimumab, Certolizumab pegol, business, Irritable bowel syndrome, medicine.drug
Abstract: Background Faecal calprotectin (Fcal) could be a non-invasive alternative to endoscopy to assess therapeutic efficacy in patients with Crohn’s disease (CD). We performed a systematic review and meta-analysis of individual data to assess the performances of FCal after anti-TNF induction therapy to predict mid-term steroids-free clinical remission (CFREM) in CD. Methods We included all the studies reporting patients with CD receiving anti-TNF agents with Fcal measurement before and after induction therapy (from 8 to 14 weeks) with follow-up > 6 months, no therapeutic intervention based on FCal during the follow-up and mid-term clinical evaluation between week 32 and week 54. CFREM was defined as CDAI < 150 and continuation of the same anti-TNF agent without steroids. Results We identified five articles including 165 patients with CD (mean age = 34.5 ± 12.8 years, median CD duration 5 years [2–12], female gender = 52.7%, active smokers = 33.3%, prior bowel resection = 25.6%, CD location (L1 = 32.1%, L2 = 15.8%, L3 = 52.1%), perianal lesions = 22.4%). The patients were treated with infliximab (50.9%), adalimumab (47.3%) or certolizumab (1.8%), and received concomitant immunosuppressants in 48.5% of the patients. Mid-term CFREM was achieved in 57.3% of the patients. Fcal level after anti-TNF induction therapy was lower in patients who achieved mid-term CFREM (100 µg/g [48–267] compared with those who did not (491 µg/g [165–856]; p < 0.001). The relative decrease of Fcal between before and after induction therapy was also associated with mid-term CFREM (p = 0.022). In multivariable analysis adjusted on CDAI, CRP and disease duration, FCal level (p = 0.014) and relative decrease of anti-TNF (p = 0.025) after induction were associated with mid-term CFREM. Cut-off values between 200 and 400 µg/g showed close performances to predict mid-term CFREM. FCal Conclusion The improvement of Fcal after anti-TNF induction therapy is predictive of mid-term CFREM in patients with IBD. The combination of clinical remission, CRP normalisation and FCal improvement should be a therapeutic target in patients with CD. Our work highlighted the need of international standardisation of Fcal measurement.
Published: 2020

36. Costs of Crohnʼs Disease According to Severity States in France

Author: Bernard Flourié, Guillaume Cadiot, Edouard Louis, Benjamin Pariente, Fady Daniel, Philippe Marteau, Jacques Moreau, Stéphane Nancey, Mathurin Fumery, Eric Lerebours, Bernard Duclos, Gilles Boschetti, Yoram Bouhnik, Arnaud Bourreille, Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Registre EPIMAD, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Departement de Gastroentérologie, Hôpital de Hautepierre [Strasbourg], Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), CIC Plurithématique de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ministère des Affaires sociales et de la Santé-Direction générale de l'offre de soins (DGOS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépato-gastroentérologie (CHU Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université de Liège, Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Total cost, [SDV]Life Sciences [q-bio], clinical course, costs, Severity of Illness Index, Young Adult, 03 medical and health sciences, Indirect costs, 0302 clinical medicine, Cost of Illness, Crohn Disease, Gastrointestinal Agents, Severity of illness, medicine, health economics, Humans, Immunology and Allergy, Prospective Studies, Child, Prospective cohort study, health care economics and organizations, Aged, Crohn's disease, Gastrointestinal agent, Models, Statistical, business.industry, severity states, Gastroenterology, Health Care Costs, Middle Aged, medicine.disease, Infliximab, Hospitalization, Child, Preschool, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Observational study, France, business, medicine.drug
Abstract: International audience; Background: To describe the medico-economic characteristics of Crohn's disease (CD), we implemented a multicenter study in France. Methods: From 2004 to 2006, disease severity states, direct (hospital and extra hospital) and indirect costs were prospectively collected over 1 year in patients with CD naive from anti-tumor necrosis factor alpha (infliximab) at inclusion. Economic valorization was performed from the French Social Insurance perspective, and a statistical modeling over 10 years was performed. Results: In 341 patients, the mean total costs of management were epsilon 6024 per year (epsilon 4675 for direct costs). As compared to patients in remission, costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery (SURG). The most important expense items were medical and surgical hospitalizations (56% of total costs), including cost of infliximab (36% of hospitalization costs, i.e., 20% of total costs), indirect costs (22%), and drugs (11%). The statistical modeling over 10 years showed that most of the clinical course was spent in drug-responsive state (54%) with 26% of costs or in remission (32%) with 11% of costs; time spent in a SURG state was small (3.2%) but generated 48% of total costs. Conclusions: Before the introduction of self-injectable anti-tumor necrosis factor alpha, the most important expenses were supported by hospitalizations, explaining why the most costly states were for patients requiring SURG or dependent on inhospital administrated drugs. Projected data show that most time is spent in a stabilized state with appropriate treatments or in remission, and that costs associated with SURG are high.
Published: 2016

37. Association Between Microscopic Lesions at Ileal Resection Margin and Recurrence After Surgery in Patients With Crohn’s Disease

Author: Alexandra Traverse-Glehen, Nassim Hammoudi, Olivier Corcos, Philippe Marteau, Julien Loreau, Mariane Maillet, Martine Leconte, Jonathan Catry, Yves Francois, Najim Chafai, Xavier Dray, Marjolaine Ngollo, Philippe Seksik, Pierre Cattan, Benjamin Pariente, Nicolas Munoz-Bongrand, Peggy Falgon, Stéphane Nancey, Nathan Beaupel, Isabelle Nion-Larmurier, Andrée Nisard, Christophe Attencourt, Emmanuel Tiret, Ulrika Chaput, Denis Chatelain, Marion Chauvenet, Dominique Cazals-Hatem, Eddy Cotte, Laurent Beaugerie, Madeleine Bezault, Mircea Chirica, Gilles Boschetti, Sarah Boyer, Loic Brot, Julien Kirchgesner, Hugo Bottois, Anne Dubois, Magali Svrcek, Yoram Bouhnik, Jean-Marc Gornet, Rachid Kaci, Brice Gergaud, Carmen Stefanescu, Helene Corte, Claire Auzolle, Jean-Louis Dupas, Juliette Joubert Zakeyh, Leila Chedouba, Amine Rahili, Elodie Quévrain, Charles Sabbagh, Lionel Le Bourhis, Maria Nachury, Anne Bourrier, Nathalie Guedj, Florence Renaud, Helena Hadjisavvas, Charlotte Gardair, Gilles Bommelaer, Céline Grand, Xavier Treton, Xavier Jouven, Anthony Buisson, Jérémie H. Lefevre, Paul Hofmann, Stéphanie Patouraux, Jérôme Filippi, Xavier Hébuterne, Driffa Moussata, Clotilde Baudry, Nelson Lourenco, Marion Goutte, Harry Sokol, Victor Chardiny, My-Linh Tran-Minh, Bernard Flourié, Pierre Desreumaux, Catherine Godfraind, Coralie Sommeville, Mathurin Fumery, Nicolas Barnich, Joëlle Bonnet, Anne-Laure Charlois, Dilek Coban, Leon Magiorri, Yves Panis, Matthieu Allez, Jean-François Fléjou, Franck Brazier, M. Ferron, Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Département de Pathologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Hôpital Beaujon [AP-HP], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Cryptitis, Ileum, REMIND Trial, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Recurrence, Interquartile range, medicine, Humans, Prospective Studies, Colectomy, Digestive System Surgical Procedures, Outcome, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Prognostic Factor, IBD Surgery, Anastomosis, Surgical, Gastroenterology, Margins of Excision, Histology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Odds ratio, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Endoscopy, Surgery, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Complication, business
Abstract: International audience; Background and AimsDifferent types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn’s disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence.MethodsWe collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery.ResultsSix months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026).ConclusionIn patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.
Published: 2019

38. Dose de-escalation to adalimumab 40 mg every three weeks in patients with inflammatory bowel disease—A multicenter, retrospective, observational study

Author: Camille Zallot, Aurelien Amiot, Mathurin Fumery, Lucine Vuitton, Laurent Peyrin-Biroulet, Benjamin Pariente, Stéphane Nancey, Cédric Baumann, Anne Lamoureux, Hélène Rousseau, Guillaume Pineton de Chambrun, Gaspard Dufour, Lieven Pouillon, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Imelda General Hospital, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Claude Huriez [Lille], CHU Lille, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Université de Montpellier (UM)-CHU Saint-Eloi, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CCSD, Accord Elsevier
Subjects: Adult, Male, musculoskeletal diseases, Crohn’s disease, medicine.medical_specialty, Anti-Inflammatory Agents, Inflammatory bowel disease, Drug Administration Schedule, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Internal medicine, medicine, Adalimumab, Humans, skin and connective tissue diseases, Crohn's disease, Dose-Response Relationship, Drug, Hepatology, business.industry, Remission Induction, Gastroenterology, Endoscopy, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Ulcerative colitis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, humanities, De-escalation, 3. Good health, Discontinuation, Intestines, Treatment Outcome, 030220 oncology & carcinogenesis, Every Three Weeks, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, Drug Monitoring, business, medicine.drug
Abstract: Background Data about the outcomes after adalimumab dose de-escalation in inflammatory bowel disease (IBD) are scarce. Objectives To assess the outcomes after adalimumab dose de-escalation, and to identify potential factors associated with failure. Methods Retrospective, observational study including all IBD patients who had undergone adalimumab dose de-escalation to 40 mg every three weeks across seven GETAID centers, between June 2011 and September 2017. Failure of adalimumab dose de-escalation was defined as the need for treatment re-escalation, discontinuation of adalimumab, or clinical, biochemical and/or morphologic disease relapse. Results Fifty-six patients were identified (n = 46 Crohn’s disease, n = 10 ulcerative colitis). Median (IQR) duration of follow-up after adalimumab dose de-escalation was 15.9 (7.9–30.6) months. Adalimumab dose de-escalation was a failure in 21/56 (37.5%) patients and successful in 35/56 (62.5%) patients. Median (IQR) time until failure was 8.9 (4.6–15.6) months. At multivariate analysis, inactive disease at magnetic resonance imaging and/or endoscopy in the year before adalimumab dose de-escalation decreased the risk of failure with a factor five (P = 0.02). Conclusions Adalimumab dose de-escalation to 40 mg every three weeks is possible in almost two thirds of IBD patients. Objective morphologic signs of active disease should be ruled out before considering a de-escalation strategy with adalimumab.
Published: 2019

39. Crohn's Disease Mucosal Transcriptomes Highlight JAK/STAT Pathway Involvement in Postoperative Recurrence

Author: Marjolaine Ngollo, Kevin Perez, Nassim Hammoudi, Yuri Gorelik, Marc Delord, Claire Auzolle, Hugo Bottois, Dominique Cazals-Hatem, Madeleine Bezault, Stéphane Nancey, Benjamin Pariente, Xavier Treton, Mathurin Fumery, Antony Buisson, Nicolas Barnich, Philippe Seksik, REMIND Study Group Invertigators, Shai S. Shen-Orr, Lionel Le Bourhis, and Matthieu Allez
Subjects: medicine.medical_specialty, Crohn's disease, business.industry, JAK-STAT signaling pathway, medicine.disease, Gastroenterology, Ileal resection, Resection, Internal medicine, medicine, Clinical endpoint, Intestinal resection, Prospective cohort study, business, Trial registration
Abstract: Background: Crohn's disease displays heterogeneity in terms of disease location, progression and response to treatment. Most patients require an intestinal resection due to complicated disease, and a majority of them will experience disease recurrence. We aimed to characterize biological pathways driving postoperative recurrence and to identify predictors which could guide therapeutic management. Methods: In this multicentre prospective study, we conducted transcriptome analysis on ileal mucosa of CD patients undergoing ileocolonic resection. Samples were collected from the most inflamed part of the ileum (n=200), from the ileal resection margin (n=149) and in the neo-terminal ileum 6 months after surgery (n=122). The primary endpoint was postoperative endoscopic recurrence at month 6. We applied a regression model to identify gene signatures predicting for endoscopic recurrence. Findings: Molecular patterns of early endoscopic recurrence significantly differed from those observed in chronic inflammation. Gene expression analysis of the inflamed area of the surgical specimens identified clusters of CD patients. However, pathway gene signatures at the ileal margin were superior to those of the inflamed area to predict postoperative outcome. Several pathways, including JAK/STAT signalling, cell adhesion molecules and extracellular matrix protein were associated with a higher risk of endoscopic recurrence. JAK/STAT pathway activation at the ileal margin predicted early postoperative endoscopic recurrence (AUC of 0*74) and was associated with a higher of clinical relapse on the long term. A significant increase of p-STAT3 levels at the ileal margin was associated with severe endoscopic recurrence (i3, i4) compared to no recurrence (i0) (p=0*02) and moderate recurrence (i1, i2) (p=0*04). Interpretation: Gene expression analysis at the ileal margin of the surgical specimen may strongly predict postoperative outcome. The inflammatory processes associated with postoperative recurrence differ from those engaged in chronic inflammation. Activation of JAK/STAT signalling at the ileal margin of the surgical specimen is predictive of postoperative recurrence and should be specifically targeted. Trial Registration: ClinicalTrials.gov (NCT03458195). Funding Statement: This work was supported by Helmsley Charitable Trust and the Institut national de sante et de la recherche biomedical (INSERM). Declaration of Interests: SN received honoraria from MSD, Abbvie, Takeda, Janssen, HAC Pharma, Tillots, Ferring, and Novartis. BP received honoraria from AbbVie, MSD, Takeda, Janssen, Bioagaran, and Ferring. AB received honoraria from MSD, Abbvie, Ferring, Takeda, Vifor Pharma, Sanofi-Aventis, Hospira, and Janssen. XT received honoraria from Abbvie, MSD, Takeda, Ferring, Norgine, and Janssen. MF received honoraria from AbbVie, MSD, Takeda, Janssen, Pfizer, Ferring, and Boehringer. PS received honoraria from Takeda, MSD, Biocodex, Ferring and Abbvie and financial support from Takeda. MA received honoraria from Janssen, Takeda, Pfizer, MSD, Abbvie, Ferring, Amgen, Biogen, Celgene, and Genentech/Roche. All other authors have no conflict of interest regarding this study. Ethics Approval Statement: All patients provided an informed written consent. The study was approved by AFFSAPS (IDRCB: 2009-A00205-52) and the French Ethic Committee (CPP 2009/17).
Published: 2019

40. Male gender, active smoking and previous intestinal resection are risk factors for post-operative endoscopic recurrence in Crohn's disease: results from a prospective cohort study

Author: Xavier Treton, Mathurin Fumery, Claire Auzolle, Xavier Jouven, Benjamin Pariente, Philippe Marteau, Nassim Hammoudi, Carmen Stefanescu, Philippe Seksik, Anthony Buisson, My-Linh Tran-Minh, Matthieu Allez, Stéphane Nancey, INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Service d'hépato-gastroentérologie, Hospices Civils de Lyon (HCL), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pole des maladies de l'appareil digestif, gastroentérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), AP-HP Hôpital Beaujon, CHU Saint-Antoine [APHP], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Multivariate analysis, Disease, Anastomosis, Lower risk, 03 medical and health sciences, 0302 clinical medicine, medicine, Pharmacology (medical), Prospective cohort study, Male gender, ComputingMilieux_MISCELLANEOUS, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Surgery, Endoscopy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business
Abstract: BACKGROUND After ileocaecal resection for Crohn's disease (CD), inflammatory lesions frequently recur on the anastomosis and/or on the neo-terminal ileum. AIM To identify predictors of early post-operative endoscopic recurrence. METHODS From September 2010 to September 2017, the REMIND group conducted a prospective nationwide study in nine French academic centres. Data were collected at the time of surgery and endoscopy, performed 6-12 months after surgery. Endoscopic recurrence was defined as a Rutgeerts score ≥i2. Baseline factors associated with endoscopic recurrence were searched by univariate and multivariate regression analysis. RESULTS Two hundred and eighty-nine CD patients were included. Endoscopy within 1 year following surgery was performed in 225 (78%) patients (104M/121F). Mean age and disease duration were 35 (12.2) and 8.8 (8.9) years respectively. Seventy (32%) patients were active smokers at surgery. One hundred and forty-two (63%) patients received at least one anti-TNF therapy before surgery. After surgery, 40 (18%) patients received thiopurines and 66 (29%) received an anti-TNF agent. Endoscopic recurrence occurred in 107 (47%) patients. In multivariate analysis, male gender (OR = 2.48 [IC 95% 1.40-4.46]), active smoking at surgery (OR = 2.65 [IC 95% 1.44-4.97]) and previous resection (OR = 3.03 [IC 95% 1.36-7.12]) were associated with a higher risk of endoscopic recurrence. Inversely, post-operative anti-TNF treatment decreased the risk of endoscopic recurrence (OR = 0.50 [IC 95% 0.25-0.96]). CONCLUSIONS Male gender, active smoking at surgery and previous intestinal resection are associated with a higher risk of endoscopic post-operative recurrence, while post-operative anti-TNF treatment is associated with a lower risk.
Published: 2018

41. Endoscopic Detection of Small Bowel Dysplasia and Adenocarcinoma in Crohn’s Disease: A Prospective Cohort-Study in High-Risk Patients

Author: Sylvie Chevret, Marion Simon, Jean-Marc Gornet, Maria Nachury, Carmen Stefanescu, Stéphane Nancey, A Blain, David Laharie, G. D'Haens, Lucine Vuitton, Benjamin Pariente, P. Seksik, Jérôme Filippi, Jacques Cosnes, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology and Hepatology
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Adenocarcinoma, Sensitivity and Specificity, Gastroenterology, Endoscopy, Gastrointestinal, Chromoendoscopy, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Risk Factors, Internal medicine, Intestinal Neoplasms, Intestine, Small, Biopsy, medicine, Humans, Prospective Studies, Prospective cohort study, Crohn's disease, medicine.diagnostic_test, business.industry, General Medicine, Bowel resection, Middle Aged, medicine.disease, Surgery, Dysplasia, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, business, Cohort study
Abstract: Background and Aims: Crohn’s disease [CD] is associated with an increased risk of small bowel adenocarcinoma [SBA]. There are no recommendations on endoscopic screening of SBA in CD patients. The aim of this study was to evaluate the feasibility and value of endoscopic screening for SBA in CD patients at high-risk of SBA. Methods: We performed an exploratory multi-centre study in a prospective cohort of CD patients at high-risk of SBA defined as long-term small bowel disease without bowel resection for the past 10 years. Depending on the location of the disease, baseline upper and/or lower enteroscopies were performed. Random and targeted biopsies using chromoendoscopy were taken. Patients were followed-up for at least 1 year after inclusion. Results: In total, 101 patients [62 men; median age: 48 years; median duration of disease: 19 years] were recruited in ten centres. The endoscopic procedure was incomplete in 47 cases because of impassable strictures and dilation was performed in four patients. Indeterminate small bowel dysplasia was identified in two patients at endoscopic screening; SBA was confirmed in one after surgical resection. With an at least 1-year follow-up duration, two additional cases of SBA were identified in patients who underwent surgery for obstruction, resulting in a 33% sensitivity rate for SBA endoscopic screening. Conclusion: In a cohort of high-risk patients, the prevalence of dysplasia and SBA on CD was 4%. Because of its low sensitivity, endoscopic screening cannot be recommended for surveillance in CD patients at high-risk of SBA.
Published: 2016

42. Su1933 FAECAL CALPROTECTIN AS THERAPEUTIC TARGET IN PATIENTS WITH CROHN'S DISEASE TREATED WITH ANTI-TNF: A META-ANALYSIS OF INDIVIDUAL DATA

Author: Gilles Boschetti, Stéphane Nancey, Bruno Pereira, Anthony Buisson, Daniela Pugliese, Pauliina Molander, Alia Mami, and Islaine Nogueira
Subjects: medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Gastroenterology, medicine.disease, Faecal calprotectin, Internal medicine, Meta-analysis, Individual data, Medicine, Tumor necrosis factor alpha, In patient, business
Published: 2020

43. P675 CT-Scout platform, the digital solution to boost patient recruitment in inflammatory bowel disease clinical trials: A multicentre prospective observational comparative study

Author: Aurelien Amiot, Y. Bouhnik, D. Laharie, Xavier Hébuterne, C Tanasa Stefanescu, Xavier Roblin, Stéphane Nancey, N Sabbah, M Raith, L Peyrin Biroulet, and Arnaud Bourreille
Subjects: Crohn's disease, medicine.medical_specialty, Surrogate endpoint, business.industry, Gastroenterology, General Medicine, medicine.disease, Inflammatory bowel disease, Ulcerative colitis, Patient recruitment, Clinical trial, Internal medicine, Etrolizumab, medicine, Observational study, business
Abstract: Background The main issue to validating new molecules in the field of IBD is insufficient patient enrollment into clinical trials, resulting in premature trials termination and cost increase. CT-SCOUT™ platform is a web-based solution to help clinicians to pre-screen potential candidates and facilitating the coordination of the research team. Our aim was to compare the number of patients enrolled in IBD clinical trials in sites equipped or not with CT-SCOUT™. Methods We conducted a prospective, multicenter, open-label, observational study in sites participating to phase 3 trials evaluating the efficacy and safety of etrolizumab in ulcerative colitis (UC, Hickory) and in Crohn’s disease (CD, Bergamot). Recruitment figures were provided by the sponsor, and we considered the 21 French sites equipped with CTscout and 134 sites in other countries not equipped with CT-SCOUT™. The primary endpoint was the mean number of patients randomised per site in both trials. Secondary endpoints included a mean number of patients randomised in each study. Patients screened and those finally randomised were compared in sites equipped and non-equipped using one-way ANOVA followed by post-hoc Tukey test and Mann–Whitney test. Results During the observational period of 40 months (September 2015–December 2018), 644 and 289 patients were screened and randomised in Hickory and/or Gardenia, respectively. There were 307 and 149 patients in 78 sites for Hickory, and 337 and 140 patients for Bergamot in 102 sites. The mean numbers of screened and randomised patients in CT-SCOUT™ equipped sites vs. non-equipped are given in the table. The mean number of patients randomised in Hickory in CT-SCOUT™ sites increased by 4.0 folds as compared with non-equipped sites (p < 0.001). The mean number of patients randomised in Bergamot in CT-SCOUT™ equipped sites has been increased by 1.9-folds as compared with non-equipped sites (p = 0.009). Conclusion This multicentric study demonstrated a significant increase in patient recruitment in IBD clinical trials. Randomisation rates were twice to four times higher in equipped sites compared with non-equipped ones. CT-SCOUT™ appears to be a promising digital solution to the global issue of patient enrollment in clinical trials.
Published: 2020

44. Prevalence of

Author: Guillaume, Le Baut, Claire, O'Brien, Paul, Pavli, Maryline, Roy, Philippe, Seksik, Xavier, Tréton, Stéphane, Nancey, Nicolas, Barnich, Madeleine, Bezault, Claire, Auzolle, Dominique, Cazals-Hatem, Jérome, Viala, Matthieu, Allez, Jean-Pierre, Hugot, and Anne, Dumay
Subjects: Yersinia Infections, gut microbiota, ileal mucosa, molecular test, Polymerase Chain Reaction, Yersinia, Crohn's disease, Cellular and Infection Microbiology, Crohn Disease, DNA Gyrase, Ileum, Prevalence, Humans, mucosal immune system, innate immunity, Original Research
Abstract: Yersinia are common contaminants of food products, but their prevalence in the human gut is poorly documented. Yersinia have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gyrB gene of Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and the inv gene of Y. pseudotuberculosis. We analyzed a total of 470 ileal samples taken from 338 participants (262 CD patients and 76 controls) belonging to three independent cohorts. All patients and controls were phenotyped and genotyped for the main CD susceptibility variants: NOD2, ATG16L1, and IRGM. Yersinia were found in 7.7% of ileal samples (respectively 7.9 and 7.6% in controls and CD patients) corresponding to 10% of participants (respectively 11.8 and 9.5% in controls and CD patients). Y. enterocolitica, Y. pseudotuberculosis and Y. intermedia were the most frequently identified species. The bacteria were more frequent in resected specimens, lymph nodes and Peyer's patches. Yersinia were no more likely to be detected in CD tissues than tissues from inflammatory and non-inflammatory controls. CD patients treated with immunosuppressants were less likely to be Yersinia carriers. In conclusion, this work shows that Yersinia species are frequently found at low levels in the human ileum in health and disease. The role of Yersinia species in this ecosystem should now be explored.
Published: 2018

45. IBD-INFO Questionnaire: A Multicenter French Up-to-Date Survey of Patient Knowledge in Inflammatory Bowel Disease

Author: Anne-Laure Charlois, Nicolas Mathieu, Emilie Del Tedesco, Joshua N Borgerding, Stéphane Nancey, Gilles Boschetti, Nicolas Williet, Pauline Danion, Xavier Roblin, Bernard Flourié, Anthony Buisson, Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'Hépato-gastroentérologie [CHU Saint-Etienne], Hepato-Gastroenterology, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), and Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)
Subjects: Adult, Male, Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Multivariate analysis, Cross-sectional study, Disease, Logistic regression, Inflammatory bowel disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Patient Education as Topic, Pregnancy, Risk Factors, Surveys and Questionnaires, Internal medicine, Humans, Immunology and Allergy, Medicine, Translations, Prospective Studies, Young adult, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Crohn's disease, business.industry, Gastroenterology, Reproducibility of Results, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Middle Aged, Inflammatory Bowel Diseases, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, digestive system diseases, 3. Good health, Cross-Sectional Studies, Logistic Models, 030220 oncology & carcinogenesis, Multivariate Analysis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, 030211 gastroenterology & hepatology, France, business
Abstract: International audience; Background: It has been demonstrated in many chronic conditions, including inflammatory bowel disease (IBD), that better patient knowledge about pathology and treatment improves the course and management of disease. The aim of this study was to develop an updated self-questionnaire to assess patients' level of knowledge of IBD. Methods: The IBD-INFO included 3 parts: an original part (Q1) and 2 parts from the translation of the preexisting questionnaires Crohn's and Colitis Knowledge score (CCKNOW) (Q2) and Crohn's and Colitis Pregnancy Knowledge score (CCPKNOW) (Q3). The reliability and discriminatory ability of the questionnaire were validated in 3 groups of non-IBD volunteers with various theoretical knowledge levels. The final questionnaire (64 validated questions) was then tested on 364 in- and out- IBD patients from 4 French university hospitals. The score for each part of the questionnaire was calculated, and factors associated with low scores were identified by univariate and multivariate logistic regression analyses. Results: The scores obtained by the 3 non-IBD volunteer groups differed significantly (P \textless 0.0001), and the IBD-INFO questionnaire showed excellent internal reliability and consistency (α = 0.98). The median total score obtained by the IBD patients was 27/64 (range, 0-59), and scores for Q1, Q2, and Q3 were, respectively, 10/23 (range, 0-21), 11/24 (range, 0-23), and 4/17 (range, 0-16). In multivariate analysis, lack of a university degree, not being a member of a patient association, not receiving anti-tumor necrosis factor alpha (anti-TNFα) treatment, duration of IBD
Published: 2018

46. P167 The variation of faecal calprotectin level within the first months after bowel resection is predictive of endoscopic postoperative recurrence in patients with Crohn’s disease

Author: L Peyrin-Biroulet, Bruno Pereira, Benjamin Pariente, Mathurin Fumery, A Buisson, Xavier Roblin, Mathilde Boube, Maud Reymond, Xavier Hébuterne, R Minet-Quinard, Stéphane Nancey, D. Laharie, Gilles Bommelaer, and C. Allimant
Subjects: medicine.medical_specialty, Crohn's disease, business.industry, medicine.medical_treatment, Gastroenterology, General Medicine, Bowel resection, medicine.disease, Faecal calprotectin, Internal medicine, medicine, In patient, business
Published: 2019

47. P115 Monitoring faecal calprotectin at 3 months post-surgery is useful to predict further postoperative endoscopic recurrence in Crohn's disease

Author: Stéphane Nancey, Marion Chauvenet, F Veyre, Camille Meunier, Xavier Roblin, P Danion, Gilles Boschetti, Bernard Flourié, C Cuerq, and A Mialon
Subjects: Crohn's disease, medicine.medical_specialty, business.industry, Internal medicine, Gastroenterology, medicine, General Medicine, Post surgery, medicine.disease, business, Faecal calprotectin
Published: 2019

48. P226 Systematic review with meta-analysis of individual data: impact of cut-off values on the performance of faecal calprotectin to detect endoscopic recurrence after intestinal resection in patients with Crohn’s disease

Author: L Peyrin-Biroulet, A Buisson, Mathieu Uzzan, T Yamamoto, Gilles Boschetti, Julien Kirchgesner, E Domenech, and Stéphane Nancey
Subjects: medicine.medical_specialty, Crohn's disease, business.industry, Gastroenterology, General Medicine, medicine.disease, Faecal calprotectin, Internal medicine, Meta-analysis, Individual data, medicine, In patient, Intestinal resection, business
Published: 2019

49. Predictive Models of Therapeutic Response to Vedolizumab: A Novel Step into Personalized Medicine in Crohn's Disease?

Author: Pauline Veyrard, Gilles Boschetti, Xavier Roblin, and Stéphane Nancey
Subjects: Crohn's disease, business.industry, Gastroenterology, Bioinformatics, medicine.disease, Antibodies, Monoclonal, Humanized, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, Clinical Trials, Phase III as Topic, Crohn Disease, Predictive Value of Tests, Immunology and Allergy, Medicine, Humans, 030211 gastroenterology & hepatology, 030212 general & internal medicine, Personalized medicine, Precision Medicine, business, medicine.drug
Published: 2017

50. Anti-TNF for post-operative prevention in Crohn's disease: the detection of anti-drug antibodies at time of surgery is associated with an increased risk of endoscopic recurrence

Author: Pascal Houzé, Anthony Buisson, Yoram Bouhnik, Mathurin Fumery, Fayçal Djenidi, Philippe Marteau, Claire Auzolle, Benjamin Pariente, Stéphane Nancey, My-Linh Tran-Minh, Matthieu Allez, Philippe Seksik, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Biochimie [AP-HP Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Hôpital Claude Huriez [Lille], CHU Lille, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], and European Crohn’s and Colitis Organisation
Subjects: Drug, medicine.medical_specialty, Crohn's disease, Hepatology, biology, business.industry, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, Increased risk, 030220 oncology & carcinogenesis, medicine, biology.protein, 030211 gastroenterology & hepatology, Tumor necrosis factor alpha, Post operative, Antibody, business, ComputingMilieux_MISCELLANEOUS, media_common
Abstract: P420; International audience
Published: 2017

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