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Dalal RS, Clarke LM, Carlin A, Cabral H, Allegretti JR. Real-World Comparison of Effectiveness, Treatment Persistence, and Safety of First-Line Advanced Therapies at 1 Year for Ulcerative Proctitis. Inflamm Bowel Dis 2025; 31:1174-1177. [PMID: 39301678 DOI: 10.1093/ibd/izae215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Indexed: 09/22/2024]
Abstract
Lay Summary
In this retrospective cohort study, vedolizumab was associated with higher odds of steroid-free clinical remission at 1 year compared to anti-TNF agents for bio-naïve patients with ulcerative proctitis.
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Affiliation(s)
- Rahul S Dalal
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lindsay M Clarke
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Alex Carlin
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Heidy Cabral
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jessica R Allegretti
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Dubian S, Yzet C, Brazier F, Yzet T, Hautefeuille V, Decrombecque C, Bocquillon Q, Richard N, Buisson A, Meynier J, Fumery M. Fecal calprotectin, intestinal ultrasound, and their combination for the diagnosis of inflammatory bowel disease. Clin Res Hepatol Gastroenterol 2025; 49:102549. [PMID: 39909306 DOI: 10.1016/j.clinre.2025.102549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 01/30/2025] [Accepted: 02/03/2025] [Indexed: 02/07/2025]
Abstract
BACKGROUND We aimed to evaluate the diagnostic accuracy of fecal calprotectin (FC) and intestinal ultrasound (IUS), independently and in combination, as screening tools for adults with suspected IBD to reduce the number of unnecessary endoscopic procedures. METHODS We conducted a retrospective monocentric study that included consecutive adult patients with (i) ileocolonoscopy for suspected IBD between January 2021 and June 2023 who had either (ii) IUS and/or (iii) a FC test within 6 weeks. Bowel wall thickness (BWT) and the color Doppler signal (CDS) were evaluated for all segments. The presence of lymphadenopathy, loss of stratification, stricture, and fistula were also recorded. RESULTS In total, 119 patients with a median age of 32 years (IQR, 24.0-41.0) were included. The most common symptoms were abdominal pain (n = 88, 75 %) and chronic diarrhea (n = 89, 75 %). Among the 119 patients, 74 (62 %) had IUS, 101 (82 %) had a FC test, and 56 (47 %) had both. Forty patients (34 %) had a diagnosis of IBD, including 31 (26 %) with CD and 9 (8 %) with UC. By ROC curve analysis, the best threshold of FC to diagnose IBD was 117 ug/g (Se 97 %, Sp 73 %, PPV 67 %, NPV 98 %, AUC 0.88, 95 %CI [0.81; 0.94], p = 0.006). Using this threshold, only 3 % of patients were misclassified as non-IBD. Screening by measuring FC levels would result in a 48 % reduction in the number of adults requiring endoscopy. Abnomal IUS was significantly associated with a diagnosis of IBD (OR 5.6, 95 %IC [2.1;16.2], P = 0.0008). The association of a BWT>3 mm and a positive CDS was associated with a Se, Sp, PPV, and NPV of 48 %, 100 %, 100 %, and 75 %, respectively, but 52 % of patients were misclassified as non-IBD. The combination of a BWT>3 mm, CDS, and FC>117 ug/g had a Se, Sp, PPV, and NPV of 44 %, 100 %, 100 %, and 69 %, respectively. For patients with a normal IUS and FC<117 ug/g, 4 % were misclassified as non-IBD. CONCLUSIONS The combination of FC and IUS is a useful screening strategy to identify patients who truly require endoscopy for suspected IBD. Calprotectin is a highly effective test for ruling out IBD. Conversely, relying solely on IUS lacks the discriminative power to safely rule out IBD. However, it shows a high PPV and is a potent tool for diagnosing IBD.
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Affiliation(s)
- Serge Dubian
- Department of Gastroenterology, Amiens University hospital, and Université de Picardie, France
| | - Clara Yzet
- Department of Gastroenterology, Amiens University hospital, and Université de Picardie, France
| | - Franck Brazier
- Department of Gastroenterology, Amiens University hospital, and Université de Picardie, France
| | - Thierry Yzet
- Department of Radiology, Amiens University hospital, and Université de Picardie, France
| | - Vincent Hautefeuille
- Department of Gastroenterology, Amiens University hospital, and Université de Picardie, France
| | - Catherine Decrombecque
- Department of Gastroenterology, Amiens University hospital, and Université de Picardie, France
| | - Quentin Bocquillon
- Department of Gastroenterology, Amiens University hospital, and Université de Picardie, France
| | - Nicolas Richard
- Department of Gastroenterology, Amiens University hospital, and Université de Picardie, France
| | - Anthony Buisson
- Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Service d'Hépato-Gastroentérologie, Clermont-Ferrand, France
| | | | - Mathurin Fumery
- Department of Gastroenterology, Amiens University hospital, and Université de Picardie, France.
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Richard N, Leroyer A, Ley D, Dupont C, Bertrand V, Wils P, Gower-Rousseau C, Turck D, Guillon N, Sarter H, Savoye G, Fumery M. Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study. Dig Liver Dis 2025; 57:584-594. [PMID: 39322448 DOI: 10.1016/j.dld.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/03/2024] [Accepted: 09/04/2024] [Indexed: 09/27/2024]
Abstract
INTRODUCTION Patients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis. METHODS All patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included. RESULTS A total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002). CONCLUSION The risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.
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Affiliation(s)
- Nicolas Richard
- Univ Rouen Normandie, INSERM, ADEN UMR1073, "Nutrition, Inflammation and microbiota-gut-brain axis", CHU Rouen, Department of Gastroenterology, F-76000 Rouen, France.
| | - Ariane Leroyer
- Department of Public Health, Epidemiology, and Economic Health, EPIMAD Registry, Regional House of Clinical Research, Lille University Hospital, Lille, France; Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research, in Inflammation, F-59000 Lille, France
| | - Delphine Ley
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research, in Inflammation, F-59000 Lille, France; Department of Paediatrics, Lille University Hospital, F-59000 Lille, France
| | - Claire Dupont
- Gastroenterology Unit, Caen University Hospital, Caen, France
| | | | - Pauline Wils
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research, in Inflammation, F-59000 Lille, France; Lille University Hospital, Gastroenterology, Lille, France
| | | | - Dominique Turck
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research, in Inflammation, F-59000 Lille, France; Department of Paediatrics, Lille University Hospital, F-59000 Lille, France
| | - Nathalie Guillon
- Department of Public Health, Epidemiology, and Economic Health, EPIMAD Registry, Regional House of Clinical Research, Lille University Hospital, Lille, France
| | - Hélène Sarter
- Department of Public Health, Epidemiology, and Economic Health, EPIMAD Registry, Regional House of Clinical Research, Lille University Hospital, Lille, France; Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research, in Inflammation, F-59000 Lille, France
| | - Guillaume Savoye
- Univ Rouen Normandie, INSERM, ADEN UMR1073, "Nutrition, Inflammation and microbiota-gut-brain axis", CHU Rouen, Department of Gastroenterology, F-76000 Rouen, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens university Hospital, Amiens, France
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Sarter H, Kirschgesner J, Beaugerie L, Buisson A, Gower-Rousseau C, de Pouvourville G. Quality of life of inflammatory bowel diseases patients in france with EQ-5D-5 L: the QALY-MICI study. Qual Life Res 2025; 34:405-416. [PMID: 39470874 DOI: 10.1007/s11136-024-03821-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/21/2024] [Indexed: 11/01/2024]
Abstract
PURPOSE This study aimed to document utility values and the Visual Analog Scale (VAS) with the 5-level version of the EQ-5D questionnaire in a large sample of patients with inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). METHODS QALY-MICI was a cross-sectional survey across three sources in France. Data were collected between 2019 and 2022 for patients 18 and over. The EQ-5D-5 L, the EQ-VAS, the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Harvey-Bradshaw Index (HBI) for CD, and the Walmsley Index for UC (SCCAI) were collected. RESULTS A total of 2,841 patients aged over 18 were recruited (1785 with CD, 1056 with UC). The mean age was 40.2 (SD 14.3). The time since diagnosis was 6 years and over for 61.9% of patients. The most impacted dimensions were usual activities, anxiety/ depression, and pain/ discomfort. The mean utility value was 0.863 (SD 0.172) versus 0.905 (SD 0.158) in the French population (p = 0.007). The mean VAS value was 68 (SD 19.2) versus 73.4 (SD 22.2) in the general population (p = 0.016). Utility values and VAS were similar for CD and UC and higher for men. There was a strong positive correlation between utility values, the VAS, and the SIBDQ score, and a negative correlation between the HBI and the SCCAI. The SIBDQ score and disease activity were the main predictors of utility and VAS. CONCLUSION The QALY-MICI is, to our knowledge, the first study documenting utility values and VAS using the EQ-5D-5 L questionnaire on a large sample, with a comparison to the general population.
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Affiliation(s)
- H Sarter
- Public Health, Epidemiology and Economic Health Unit, CHU Lille, EPIMAD Registry, Maison Régionale de la Recherche Clinique, Lille, F-59000, France
| | - J Kirschgesner
- Department of Gastroenterology, Hôpital Saint-Antoine, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
| | - L Beaugerie
- Department of Gastroenterology, Hôpital Saint-Antoine, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
| | | | - C Gower-Rousseau
- Public Health Unit, Hôpital Robert Debré, Reims University Hospital, Reims, France
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Sarter H, Crétin T, Savoye G, Fumery M, Leroyer A, Dauchet L, Paupard T, Coevoet H, Wils P, Richard N, Turck D, Ley D, Gower-Rousseau C. Incidence, prevalence and clinical presentation of inflammatory bowel diseases in Northern France: a 30-year population-based study. THE LANCET REGIONAL HEALTH. EUROPE 2024; 47:101097. [PMID: 39478988 PMCID: PMC11522416 DOI: 10.1016/j.lanepe.2024.101097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/27/2024] [Accepted: 09/30/2024] [Indexed: 11/02/2024]
Abstract
Background In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn's disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 105 person-years, respectively. The incidence of CD increased from 5.1/105 in 1988-1990 to 7.9/105 in 2015-2017 (annual percent change (APC): +1.9%, p < 0.0001). The incidence of UC increased from 4.5/105 to 6.1/105 (APC: +1.3%, p < 0.0001). The largest increase was observed in children (+4.3% in CD, p < 0.0001; +5.4% in UC, p < 0.0001) followed by young adults aged 17-39 years (+1.9% in CD, p < 0.0001; +1.5% in UC, p < 0.0001). The increase in UC incidence was significantly higher in women than in men (+1.9% in women, +0.8% in men; p = 0.006). We estimated that in our area, by 2030, nearly 0.6% of the population will have IBD. Interpretation The persistent increase of IBD incidence among children and young adults but also in women with UC in Northern France, suggests the persistence of substantial predisposing environmental factors. Funding Santé Publique France; INSERM; Amiens, Lille and Rouen University Hospitals.
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Affiliation(s)
- Hélène Sarter
- CHU Lille, Public Health, Epidemiology and Economic Health Unit, EPIMAD Registry, Maison Régionale de la Recherche Clinique, F-59000 Lille, France
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille F-59000, France
| | - Thibaut Crétin
- Gastroenterology Unit, CHU Lille, University of Lille, Lille F-59000, France
- Gastroenterology Unit, Saint Philibert Hospital, Catholic University, Lille, France
| | - Guillaume Savoye
- Univ Rouen Normandie, INSERM, ADEN UMR1073, “Nutrition, Inflammation and Microbiota-gut-brain axis”, CHU Rouen, Department of Gastroenterology, Rouen F-76000, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Hospital, and Peritox, UMRI01, Université de Picardie Jules Verne, Amiens, France
| | - Ariane Leroyer
- CHU Lille, Public Health, Epidemiology and Economic Health Unit, EPIMAD Registry, Maison Régionale de la Recherche Clinique, F-59000 Lille, France
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille F-59000, France
| | - Luc Dauchet
- CHU Lille, Public Health, Epidemiology and Economic Health Unit, EPIMAD Registry, Maison Régionale de la Recherche Clinique, F-59000 Lille, France
- Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement, Lille F-59000, France
| | | | - Hugues Coevoet
- Gastroenterology Unit, Les Bonnettes Private Hospital, Arras, France
| | - Pauline Wils
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille F-59000, France
- Gastroenterology Unit, CHU Lille, University of Lille, Lille F-59000, France
| | - Nicolas Richard
- Univ Rouen Normandie, INSERM, ADEN UMR1073, “Nutrition, Inflammation and Microbiota-gut-brain axis”, CHU Rouen, Department of Gastroenterology, Rouen F-76000, France
| | - Dominique Turck
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille F-59000, France
- CHU Lille, Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, Lille F-59000, France
| | - Delphine Ley
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille F-59000, France
- CHU Lille, Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, Lille F-59000, France
| | - Corinne Gower-Rousseau
- Research and Public Health Unit, Robert Debré Hospital, Reims University Hospital, France
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Peyrin-Biroulet L, Dubinsky MC, Sands BE, Panés J, Schreiber S, Reinisch W, Feagan BG, Danese S, Yarur AJ, D’Haens GR, Goetsch M, Wosik K, Keating M, Lazin K, Wu J, Modesto I, McDonnell A, Bartolome L, Vermeire S. Efficacy and Safety of Etrasimod in Patients with Moderately to Severely Active Isolated Proctitis: Results From the Phase 3 ELEVATE UC Clinical Programme. J Crohns Colitis 2024; 18:1270-1282. [PMID: 38613425 PMCID: PMC11324338 DOI: 10.1093/ecco-jcc/jjae038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/08/2024] [Indexed: 04/15/2024]
Abstract
BACKGROUND AND AIMS Pivotal trials in ulcerative colitis have historically excluded patients with isolated proctitis. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis. This post hoc analysis assessed efficacy and safety of etrasimod 2 mg once daily in patients with isolated proctitis (centrally read) from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. METHODS Patients, including those with isolated proctitis (<10 cm rectal involvement) who met all other inclusion criteria in ELEVATE UC 52 and ELEVATE UC 12, were randomised 2:1 to receive etrasimod or placebo. Primary, secondary and other identified efficacy endpoints and safety were assessed. RESULTS We analysed data from 64 and 723 patients at Week 12 (both trials pooled), and 36 and 397 patients at Week 52 (ELEVATE UC 52 only) with isolated proctitis and more extensive colitis (≥10 cm rectal involvement), respectively. Patients with isolated proctitis receiving etrasimod demonstrated significant improvements versus placebo, including clinical remission rates at Weeks 12 (42.9% vs 13.6%) and 52 (44.4% vs 11.1%), endoscopic improvement (52.4% vs 22.7%) at Week 12 and bowel urgency numerical rating scale score at Week 12 (all p < 0.01). Generally similar trends were observed in patients with more extensive colitis. Safety was consistent across subgroups, with no new findings. CONCLUSIONS Etrasimod demonstrated significant improvements versus placebo in patients with isolated proctitis, and those with more extensive disease, in most efficacy endpoints at Week 12 and 52. Clinicaltrials.gov: NCT03945188; NCT03996369.
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Affiliation(s)
- Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada
| | - Marla C Dubinsky
- Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Julian Panés
- Formerly Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Stefan Schreiber
- Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany
| | - Walter Reinisch
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Brian G Feagan
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
- Alimentiv Inc, London, ON, Canada
| | - Silvio Danese
- Division of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita Salute San Raffaele University, Milan, Italy
| | - Andres J Yarur
- Inflammatory Bowel Disease Center and Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Geert R D’Haens
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | | | | | | | | | | | | | | | | | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
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Fumery M, Dupont C, Ley D, Savoye G, Bertrand V, Guillon N, Wils P, Gower-Rousseau C, Sarter H, Turck D, Leroyer A. Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study. Dig Liver Dis 2024; 56:21-28. [PMID: 37137808 DOI: 10.1016/j.dld.2023.04.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 04/13/2023] [Accepted: 04/14/2023] [Indexed: 05/05/2023]
Abstract
BACKGROUND Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. METHODS All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. RESULTS Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. CONCLUSION In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.
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Affiliation(s)
- Mathurin Fumery
- Amiens University Hospital, Gastroenterology, Amiens, France.
| | - Claire Dupont
- Caen University hospital, Pediatrics, Gastroenterology, France
| | - Delphine Ley
- CHU Lille, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Lille, France; Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | | | | | - Nathalie Guillon
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France; Reims University Hospital, Gastroenterology, Reims, France
| | - Pauline Wils
- Lille University Hospital, Gastroenterology, EPIMAD registry, Regional house of clinical research, F-59000 Lille, France
| | | | - Helene Sarter
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France; Lille Hospital and University, Public Health, Epidemiology and Economic Health, France
| | - Dominique Turck
- CHU Lille, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Lille, France; Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Ariane Leroyer
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France; Lille Hospital and University, Public Health, Epidemiology and Economic Health, France
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Sarter H, Savoye G, Marot G, Ley D, Turck D, Hugot JP, Vasseur F, Duhamel A, Wils P, Princen F, Colombel JF, Gower-Rousseau C, Fumery M. A Novel 8-Predictors Signature to Predict Complicated Disease Course in Pediatric-onset Crohn's Disease: A Population-based Study. Inflamm Bowel Dis 2023; 29:1793-1804. [PMID: 37266570 DOI: 10.1093/ibd/izad090] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Indexed: 06/03/2023]
Abstract
BACKGROUND The identification of patients at high risk of a disabling disease course would be invaluable in guiding initial therapy in Crohn's disease (CD). Our objective was to evaluate a combination of clinical, serological, and genetic factors to predict complicated disease course in pediatric-onset CD. METHODS Data for pediatric-onset CD patients, diagnosed before 17 years of age between 1988 and 2004 and followed more than 5 years, were extracted from the population-based EPIMAD registry. The main outcome was defined by the occurrence of complicated behavior (stricturing or penetrating) and/or intestinal resection within the 5 years following diagnosis. Lasso logistic regression models were used to build a predictive model based on clinical data at diagnosis, serological data (ASCA, pANCA, anti-OmpC, anti-Cbir1, anti-Fla2, anti-Flax), and 369 candidate single nucleotide polymorphisms. RESULTS In total, 156 children with an inflammatory (B1) disease at diagnosis were included. Among them, 35% (n = 54) progressed to a complicated behavior or an intestinal resection within the 5 years following diagnosis. The best predictive model (PREDICT-EPIMAD) included the location at diagnosis, pANCA, and 6 single nucleotide polymorphisms. This model showed good discrimination and good calibration, with an area under the curve of 0.80 after correction for optimism bias (sensitivity, 79%, specificity, 74%, positive predictive value, 61%, negative predictive value, 87%). Decision curve analysis confirmed the clinical utility of the model. CONCLUSIONS A combination of clinical, serotypic, and genotypic variables can predict disease progression in this population-based pediatric-onset CD cohort. Independent validation is needed before it can be used in clinical practice.
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Affiliation(s)
- Hélène Sarter
- Lille Hospital and University, Public Health, Epidemiology and Economic Health, EPIMAD registry, Regional house of clinical research, F-59000 Lille, France
- University of Lille, Inserm, CHU Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Guillaume Savoye
- Rouen Hospital and University, Gastroenterology Unit, EPIMAD registry, Rouen, France
| | - Guillemette Marot
- University of Lille, CHU Lille, ULR 2694-METRICS: Evaluation des Technologies de Santé et des Pratiques Médicales, F-59000 Lille, France
- Inria Lille Nord Europe, Modal, Lille, France
| | - Delphine Ley
- University of Lille, Inserm, CHU Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, F-59000 Lille, France
- Lille University Jeanne de Flandre Children's Hospital and Faculty of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille, France
| | - Dominique Turck
- University of Lille, Inserm, CHU Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, F-59000 Lille, France
- Lille University Jeanne de Flandre Children's Hospital and Faculty of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille, France
| | - Jean-Pierre Hugot
- Centre de Recherche sur l'Inflammation, UMR1149 INSERM et Université de Paris, France
- Department of Pediatric Gastroenterology, Hôpital Robert Debré, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France
| | - Francis Vasseur
- University of Lille, CHU Lille, ULR 2694-METRICS: Evaluation des Technologies de Santé et des Pratiques Médicales, F-59000 Lille, France
| | - Alain Duhamel
- University of Lille, CHU Lille, ULR 2694-METRICS: Evaluation des Technologies de Santé et des Pratiques Médicales, F-59000 Lille, France
| | - Pauline Wils
- University of Lille, Inserm, CHU Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, F-59000 Lille, France
- Gastroenterology Unit, Lille Hospital and University, Lille, France
| | | | | | - Corinne Gower-Rousseau
- Lille Hospital and University, Public Health, Epidemiology and Economic Health, EPIMAD registry, Regional house of clinical research, F-59000 Lille, France
- University of Lille, Inserm, CHU Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, F-59000 Lille, France
- Research and Public Health Unit, Reims University & Hospital, Robert-Debré Hospital, Reims, France
| | - Mathurin Fumery
- Amiens Hospital and University, Gastroenterology Unit, EPIMAD Registry, and PeriTox, UMR I-01, Amiens, France
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9
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Ley D, Leroyer A, Dupont C, Sarter H, Bertrand V, Spyckerelle C, Guillon N, Wils P, Savoye G, Turck D, Gower-Rousseau C, Fumery M. New Therapeutic Strategies Are Associated With a Significant Decrease in Colectomy Rate in Pediatric Ulcerative Colitis. Am J Gastroenterol 2023; 118:1997-2004. [PMID: 37141541 DOI: 10.14309/ajg.0000000000002316] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 04/27/2023] [Indexed: 05/06/2023]
Abstract
INTRODUCTION We evaluated the impact of immunosuppressants (IS) and antitumor necrosis factor (TNF) introduction on long-term outcomes of ulcerative colitis (UC) in a large population-based pediatric-onset cohort. METHODS All patients included in the EPIMAD registry with a diagnosis of UC made before the age of 17 years between 1988 and 2011 were followed up retrospectively until 2013. Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). RESULTS A total of 337 patients (female, 57%) diagnosed with UC were followed up during a median duration of 7.2 years (interquartile range 3.8-13.0). The IS and anti-TNF exposure rates at 5 years increased over time from 7.8% (P1) to 63.8% (P3) and from 0% (P1) to 37.2% (P3), respectively. In parallel, the risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P -trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) ( P = 0.013). The risk of disease extension at 5 years remained stable over time (P1, 36%, P2, 32%, and P3, 34%; P = 0.31, P -trend = 0.52) and between the pre-anti-TNF era (P1 + P2, 34%) and the anti-TNF era (P3, 34%) ( P = 0.92). The risk of flare-related hospitalization at 5 years significantly increased over time (P1, 16%; P2, 27%; P3, 42%; P = 0.0012, P -trend = 0.0006) and between the pre-anti-TNF era (P1 + P2, 23%) and the anti-TNF era (P3, 42%) ( P = 0.0004). DISCUSSION In parallel with the increased use of IS and anti-TNF, an important decline in the risk of colectomy in pediatric-onset UC was observed at the population level.
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Affiliation(s)
- Delphine Ley
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, CHU Lille, Lille, France
- Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Univ. Lille, Lille, France
| | - Ariane Leroyer
- Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Univ. Lille, Lille, France
- Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison Régionale de la Recherche Clinique, CHU Lille, Lille, France
| | - Claire Dupont
- Department of Pediatrics, Caen University Hospital, Caen, France
| | - Hélène Sarter
- Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Univ. Lille, Lille, France
- Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison Régionale de la Recherche Clinique, CHU Lille, Lille, France
| | | | - Claire Spyckerelle
- Department of Pediatrics, St Vincent de Paul Hospital and Lille Catholic University, Lille, France
| | - Nathalie Guillon
- Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison Régionale de la Recherche Clinique, CHU Lille, Lille, France
| | - Pauline Wils
- Gastroenterology Unit, CHU Lille, University of Lille, Lille, France
| | - Guillaume Savoye
- Gastroenterology Unit, Rouen University Hospital, UMR 1073, University of Rouen Normandy, Rouen, France
| | - Dominique Turck
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, CHU Lille, Lille, France
- Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Univ. Lille, Lille, France
| | - Corinne Gower-Rousseau
- Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Univ. Lille, Lille, France
- Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison Régionale de la Recherche Clinique, CHU Lille, Lille, France
- Research Unit and Public Health, Reims University Hospital, Reims, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Hospital, and Peritox, UMRI01, Université de Picardie Jules Verne, Amiens, France
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10
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Mortreux P, Leroyer A, Dupont C, Ley D, Bertrand V, Spyckerelle C, Guillon N, Wils P, Gower-Rousseau C, Savoye G, Fumery M, Turck D, Siproudhis L, Sarter H. Natural History of Anal Ulcerations in Pediatric-Onset Crohn's Disease: Long-Term Follow-Up of a Population-Based Study. Am J Gastroenterol 2023; 118:1671-1678. [PMID: 37104674 DOI: 10.14309/ajg.0000000000002301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023]
Abstract
INTRODUCTION Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. METHODS All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. RESULTS Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. DISCUSSION Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration.
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Affiliation(s)
| | - Ariane Leroyer
- Lille University Hospital, Public Health, Epidemiology, and Economic Health, EPIMAD Registry, Regional House of Clinical Research, Lille, France
- Lille University, Inserm, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France
| | - Claire Dupont
- Department of Pediatrics, Gastroenterology, Caen University Hospital, Caen, France
| | - Delphine Ley
- Lille University, Inserm, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France
- Department of Pediatrics, Lille University Hospital, Lille, France
| | | | | | - Nathalie Guillon
- Lille University Hospital, Public Health, Epidemiology, and Economic Health, EPIMAD Registry, Regional House of Clinical Research, Lille, France
- Lille University, Inserm, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France
| | - Pauline Wils
- Lille University Hospital, Gastroenterology, Lille, France
- Lille University, Inserm, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France
| | | | - Guillaume Savoye
- Department of Gastroenterology, Rouen University Hospital, Rouen, France
| | - Mathurin Fumery
- Department of Gastroenterology, Amiens University Hospital, Amiens, France
| | - Dominique Turck
- Lille University, Inserm, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France
- Department of Pediatrics, Lille University Hospital, Lille, France
| | - Laurent Siproudhis
- Department of Gastroenterology, Rennes University Hospital, Rennes, France
| | - Hélène Sarter
- Lille University Hospital, Public Health, Epidemiology, and Economic Health, EPIMAD Registry, Regional House of Clinical Research, Lille, France
- Lille University, Inserm, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France
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11
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Diagnostic Delay in Pediatric Inflammatory Bowel Disease: A Systematic Review. Dig Dis Sci 2022; 67:5444-5454. [PMID: 35288834 DOI: 10.1007/s10620-022-07452-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 02/14/2022] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Delays in diagnosing pediatric inflammatory bowel disease (IBD) are common, but the extent of this delay remains unclear due to variations in reported time-periods between studies. The objectives of this systematic review were to examine the extent of diagnostic delay in pediatric IBD and examine any association between specific characteristics and length of diagnostic delay. METHODS We identified studies from several medical bibliographical databases (EMBASE, Medline and CINAHL) from their inception to April 2021. Studies examining pediatric cohorts (< 18 years old) defined as having a diagnosis of Crohn's Disease (CD), ulcerative colitis (UC), or by the more general definition of IBD, and reporting a median time-period between the onset of symptoms and a final diagnosis (diagnostic delay) were included. Two reviewers selected each study, extracted data, and assessed their quality using the Newcastle-Ottawa scale. Narrative synthesis was then used to examine the extent of overall diagnostic delay and delay associated with specific sample characteristics. RESULTS Of the 10,119 studies initially identified, 24 were included in the review. The overall median diagnostic delay range was 2-10.4 months for IBD, 2.0-18.0 months for UC and 4.0-24.0 months for CD. However, for approximately two thirds of UC (68.8%) and CD (66.7%) studies, delay ranged from 2.0-3.0 and 4.0-6.3 months, respectively. A longer delay was significantly associated with several sample characteristics; however, these were too infrequently examined to draw robust conclusion on their role. CONCLUSION Children continue to wait several months for a final diagnosis of IBD, and those with CD experience longer delay than those with UC. The role of specific characteristics on delay needs further exploration.
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12
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Ley D, Leroyer A, Dupont C, Sarter H, Bertrand V, Spyckerelle C, Guillon N, Wils P, Savoye G, Turck D, Gower-Rousseau C, Fumery M. New Therapeutic Strategies Have Changed the Natural History of Pediatric Crohn's Disease: A Two-Decade Population-Based Study. Clin Gastroenterol Hepatol 2022; 20:2588-2597.e1. [PMID: 35131345 DOI: 10.1016/j.cgh.2022.01.051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 01/25/2022] [Accepted: 01/26/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We evaluated the impact of immunosuppressants (IS) and anti-tumor necrosis factor (TNF) introduction on Crohn's disease (CD) long-term outcomes in a large population-based, pediatric-onset cohort. METHODS All patients included in the EPIMAD registry with a diagnosis of CD occurring when they were younger than age 17 years and between 1988 and 2011 were followed up retrospectively until 2013. Three diagnostic periods were defined: 1988 to 1993 (period [P]1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). Medication exposure and disease outcomes were compared between the 3 diagnostic periods. RESULTS A total of 1007 patients diagnosed with CD were followed up for a median duration of 8.8 years (interquartile range, 4.6-14.2 y). The IS and anti-TNF exposure rate at 5 years increased over time from 33.9% (in P1) to 76.5% (in P3) and from 0% (in P1) to 50.5% (in P3), respectively. In parallel, the risk for intestinal resection at 5 years decreased significantly over time (P1, 35%; P2, 31%; and P3, 22%; P = .0003, Ptrend < .0001), and between the pre-anti-TNF era (P1 + P2, 32%) and the anti-TNF era (P3, 22%) (P = .0007). The risk for progression from inflammatory to stricturing behavior decreased significantly over time (P1, 27%; P2, 28%; and P3, 20%; P = .11, Ptrend = .041) and between the pre-anti-TNF era (P1 + P2, 28%) and the anti-TNF era (P3, 20%) (P = .040). The risk for a CD flare-related hospitalization at 5 years remained stable over time (P1, 31%; P2, 31%; and P3, 29%; P = .76, Ptrend = .53). CONCLUSIONS In parallel with the increased use of IS and anti-TNF, positive changes in the natural history of pediatric-onset CD were observed at the population level. A decreased risk of both intestinal resections and stricturing complications were observed during the anti-TNF era.
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Affiliation(s)
- Delphine Ley
- Centre Hospitalier et Universitaire Lille, Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, Lille, France; Univ. Lille, Inserm, Centre Hospitalier et Universitaire Lille, U1286 INFINITE-Institute for Translational Research in Inflammation, Lille, France.
| | - Ariane Leroyer
- Univ. Lille, Inserm, Centre Hospitalier et Universitaire Lille, U1286 INFINITE-Institute for Translational Research in Inflammation, Lille, France; Centre Hospitalier et Universitaire Lille, Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison Régionale de la Recherche Clinique, Lille, France
| | - Claire Dupont
- Department of Paediatrics, Caen University Hospital, Caen, France
| | - Hélène Sarter
- Univ. Lille, Inserm, Centre Hospitalier et Universitaire Lille, U1286 INFINITE-Institute for Translational Research in Inflammation, Lille, France; Centre Hospitalier et Universitaire Lille, Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison Régionale de la Recherche Clinique, Lille, France
| | | | - Claire Spyckerelle
- Department of Paediatrics, St Vincent de Paul Hospital, Lille Catholic University, Lille, France
| | - Nathalie Guillon
- Centre Hospitalier et Universitaire Lille, Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison Régionale de la Recherche Clinique, Lille, France
| | - Pauline Wils
- Centre Hospitalier et Universitaire Lille, Gastroenterology Unit, Lille, France
| | - Guillaume Savoye
- Gastroenterology Unit, Rouen University Hospital, Unité Mixte de Recherche 1073, University of Rouen Normandy, Rouen, France
| | - Dominique Turck
- Centre Hospitalier et Universitaire Lille, Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, Lille, France; Univ. Lille, Inserm, Centre Hospitalier et Universitaire Lille, U1286 INFINITE-Institute for Translational Research in Inflammation, Lille, France
| | - Corinne Gower-Rousseau
- Univ. Lille, Inserm, Centre Hospitalier et Universitaire Lille, U1286 INFINITE-Institute for Translational Research in Inflammation, Lille, France; Centre Hospitalier et Universitaire Lille, Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison Régionale de la Recherche Clinique, Lille, France; Epidemiology Unit, Robert Debré Hospital, Reims University Hospital, Reims, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Hospital, Peritox, Unité Mixte de Recherche I01, Université de Picardie Jules Verne, Amiens, France
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13
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Dupont-Lucas C, Leroyer A, Ley D, Spyckerelle C, Bertrand V, Turck D, Savoye G, Maunoury V, Guillon N, Fumery M, Sarter H, Gower-Rousseau C. Increased risk of cancer and mortality in a large French population-based paediatric-onset inflammatory bowel disease retrospective cohort. J Crohns Colitis 2022; 17:524-534. [PMID: 36316987 DOI: 10.1093/ecco-jcc/jjac166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND AND AIMS Paediatric-onset IBD (pIBD) is associated with an increased risk of cancer and mortality in adulthood. The aims of this study were to measure the incidence of cancer and mortality in patients with pIBD and identify factors associated with mortality and cancer. METHODS All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 years between 1988 and 2011 in the EPIMAD registry, were retrospectively followed until 2013 for cancer and 2015 for mortality. Standardized incidence (SIR) and mortality ratios (SMR) were estimated compared to the general population. Cox regression was used to compare effect of exposures on cancer and mortality among IBD patients. RESULTS We included 1,344 patients (52% males, 75% CD), totalising 12,957 patient-years for cancer incidence and 18,817 patient-years for mortality. There were 14 cases of cancer (median age 27.8 years) and 15 deaths (median age 28.8 years). The incidence of cancer and of mortality were increased compared to the general population: all-cancer SIR = 2.7 (95%CI: 1.5-4.8), SMR = 1.7 (95%CI: 1.0-2.8). Colorectal cancer had the highest SIR and SMR: SIR=41.2 (95%CI: 17.2-99.0), SMR=70.4 (95%CI 22.7-218.2). Cancer was associated with (HR, 95%CI): active smoking at diagnosis (5.5, 1.8-16.5), p=0.002, any exposure to anti-TNF (6.1, 1.7-22.3), p=0.0065 and exposure to combination therapy (7.4, 1.8-29.7), p=0.0047. Mortality was associated with extraintestinal manifestations (HR 4.9 (95% CI: 1.7-13.8), p=0.003). CONCLUSIONS In this large population-based cohort, patients with pIBD had an increased risk of both cancer (2.7-fold) and mortality (1.7-fold), particularly for colorectal cancer.
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Affiliation(s)
- Claire Dupont-Lucas
- Department of Paediatrics, Caen University Hospital, F-14000 Caen, France.,INSERM UMR 1073 ADEN, Institute for Biomedical Research, F-76000 Rouen, France
| | - Ariane Leroyer
- Lille Hospital and University, Public Health, Epidemiology and Economic Health, EPIMAD registry, Regional house of clinical research, F-59000 Lille, France.,Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Delphine Ley
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France.,CHU Lille, Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, F-59000 Lille, France
| | - Claire Spyckerelle
- Department of Paediatrics, St Vincent de Paul Hospital and Lille Catholic University, F-59000 Lille, France
| | - Valérie Bertrand
- Department of Paediatrics, Jacques Monod Hospital, F-76600 Le Havre, France
| | - Dominique Turck
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France.,CHU Lille, Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, F-59000 Lille, France
| | - Guillaume Savoye
- INSERM UMR 1073 ADEN, Institute for Biomedical Research, F-76000 Rouen, France.,Department of Gastroenterology, Rouen University Hospital, F-76000 Rouen, France
| | - Vincent Maunoury
- Department of Gastroenterology, Claude Huriez Hospital, Lille University Hospital, F- 59000 Lille, France
| | - Nathalie Guillon
- Lille Hospital and University, Public Health, Epidemiology and Economic Health, EPIMAD registry, Regional house of clinical research, F-59000 Lille, France.,Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Mathurin Fumery
- Department of Gastroenterology, Amiens University Hospital, F-80000 Amiens, France.,INSERM UMR I01, PERITOX, Jules Verne University of Picardy, F-80000 Amiens, France
| | - Hélène Sarter
- Lille Hospital and University, Public Health, Epidemiology and Economic Health, EPIMAD registry, Regional house of clinical research, F-59000 Lille, France.,Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Corinne Gower-Rousseau
- Lille Hospital and University, Public Health, Epidemiology and Economic Health, EPIMAD registry, Regional house of clinical research, F-59000 Lille, France.,Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France.,Epidemiology Unit, Robert Debré Hospital, Reims University Hospital, F-51100 Reims, France
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14
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Rabilloud ML, Bajeux E, Siproudhis L, Hamonic S, Pagenault M, Brochard C, Gerfaud A, Dabadie A, Viel JF, Tron I, Robaszkiewicz M, Bretagne JF, Bouguen G. Long-term outcomes and predictors of disabling disease in a population-based cohort of patients with incident Crohn's disease diagnosed between 1994 and 1997. Clin Res Hepatol Gastroenterol 2022; 46:101974. [PMID: 35691599 DOI: 10.1016/j.clinre.2022.101974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 06/05/2022] [Accepted: 06/08/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND The identification of early prognostic factors during Crohn's disease (CD) remains needed for physician decision-making to minimize structural bowel damage, which this study aimed to assess in a population-based setting. METHODS All incident cases of CD were prospectively registered from 1994 to 1997 in Brittany, a limited area of France. All charts of patients were reviewed from the diagnosis to the last clinic visit in 2015. Disabling CD course was defined according to the Saint-Antoine criteria. RESULTS Among the 331 incident cases of CD, 272 (82%) were followed-up for a median time of 12.8 years. The cumulative probability of developing stricturing or fistulizing CD was 66% at 15 years, and 107 (39%) patients underwent surgery. The cumulative probabilities of immunosuppressant and TNF antagonist use at 15 years were 37% and 22%, respectively. The cumulative risks for disabling disease and bowel damage were 74% and 71% at 15 years, respectively. Systemic symptoms and perianal lesions at diagnosis were independently associated with a disabling disease course. Perianal disease and short disease extension were associated with the onset of bowel damage. Deep ulcers was not predictive of any outcome. CONCLUSIONS A disabling disease course and bowel damage occurred early in the course of CD, which suggests the need for early diagnosis and early treatment, particularly for patients with systematic symptoms and perianal disease.
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Affiliation(s)
| | - Emma Bajeux
- Department of Public Health, University Hospital of Pontchaillou, Rennes, France
| | - Laurent Siproudhis
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), F-35000 Rennes, France
| | - Stéphanie Hamonic
- Department of Public Health, University Hospital of Pontchaillou, Rennes, France
| | | | - Charlène Brochard
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), F-35000 Rennes, France
| | - Agathe Gerfaud
- CHU Rennes, Paediatric unit, Hôpital Sud, Rennes, France
| | - Alain Dabadie
- CHU Rennes, Paediatric unit, Hôpital Sud, Rennes, France
| | - Jean-François Viel
- Department of Public Health, University Hospital of Pontchaillou, Rennes, France
| | - Isabelle Tron
- Observatoire Regional De Santé Bretagne, Rennes, France
| | | | | | - Guillaume Bouguen
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), F-35000 Rennes, France.
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15
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Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure. Dermatol Ther (Heidelb) 2022; 12:1431-1446. [PMID: 35624407 PMCID: PMC9209552 DOI: 10.1007/s13555-022-00743-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/05/2022] [Indexed: 11/03/2022] Open
Abstract
INTRODUCTION We report a comprehensive summary of the safety outcomes in adult patients with moderate-to-severe psoriasis with up to 5 years of exposure to ixekizumab. METHODS Long-term safety of the IL-17A antagonist ixekizumab was assessed from 17 randomized trials. Treatment-emergent adverse events (TEAEs)-adjusted incidence rates (IRs) per 100 patient-years (PY) within 1-year time periods through 19 March 2021 were calculated for all patients treated with at least one dose of ixekizumab. Reported cases of major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) were adjudicated. RESULTS A total of 6892 adult patients with a cumulative exposure of 18,025.7 PY were included. The IRs per 100 PY for any TEAE and serious adverse events (AEs) were 32.5 and 5.4. IR of discontinuation because of AE was 2.9. A total of 36 deaths were reported. IR of serious infections was low (1.3). There were no confirmed cases of reactivation of tuberculosis (TB). IR of Candida infections (IR 1.9) was low; most cases of Candida were localized, and no systemic cases were reported. IRs of injection site reactions and allergic/hypersensitivity were 5.9 and 5.6, respectively. No confirmed cases of anaphylaxis were observed. IRs were low for malignancies, depression, cytopenia, and MACE (all ≤ 1.2). IBD events were uncommon, although a total of 31 patients (IR 0.2) had confirmed IBD (ulcerative colitis, n = 18; Crohn disease, n = 13). Across safety topics, IRs decreased or remained constant over time. CONCLUSIONS The long-term safety profile for ixekizumab is consistent with that previously reported in patients with psoriasis. No new or unexpected safety events were detected.
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16
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Elmahdi R, Lemser CE, Thomsen SB, Allin KH, Agrawal M, Jess T. Development of Cancer Among Patients With Pediatric-Onset Inflammatory Bowel Disease: A Meta-analysis of Population-Based Studies. JAMA Netw Open 2022; 5:e220595. [PMID: 35230438 PMCID: PMC8889462 DOI: 10.1001/jamanetworkopen.2022.0595] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
IMPORTANCE Because the incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing, knowledge of the long-term risk of cancer in this patient population is required. OBJECTIVE To evaluate the relative rate of cancer among patients with pediatric-onset IBD. DATA SOURCES A comprehensive systematic search was performed of MEDLINE and Embase from the date of database inception to October 31, 2021. STUDY SELECTION All unselected, population-based cohort studies of pediatric-onset IBD assessing the risk of cancer were included. Tertiary center referrals and insurance database studies were excluded. All articles were assessed by 2 independent reviewers. DATA EXTRACTION AND SYNTHESIS The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline for data extraction and used the Newcastle-Ottawa Scale for assessment of the risk of bias and the quality of included articles. MAIN OUTCOMES AND MEASURES A random-effects model meta-analysis was conducted of included studies using the inverse-variance method to assess the relative rate of cancer overall and by IBD subtype (Crohn disease or ulcerative colitis), sex, and thiopurine exposure among patients with pediatric-onset IBD. Pooled relative rates (pRRs) along with 95% CIs were calculated for combined studies. RESULTS Of 4628 articles screened, 5 population-based studies from North America and Europe were eligible for inclusion. These studies comprised 19 812 individuals with pediatric-onset IBD followed up for 283 540 person-years in which 715 cases of cancer were identified. Meta-analysis of pRR estimates showed a 2.4-fold increased rate of cancer among patients with pediatric-onset IBD (pRR, 2.46; 95% CI, 2.06-2.93), seen among patients with Crohn disease (pRR, 2.03; 95% CI, 1.67-2.46) and those with ulcerative colitis (pRR, 2.61; 95% CI, 2.00-3.40). This increased rate is primarily due to an increased rate of liver (pRR, 55.45; 95% CI, 19.59-156.99), colorectal (pRR, 20.29; 95% CI, 15.90-25.90), and small bowel (pRR, 16.20; 95% CI, 3.52-74.66) cancers. The incidence rate of cancer among patients with pediatric-onset IBD was reported by 4 studies and ranged from 1.0 to 3.3 cases per 1000 person-years. CONCLUSIONS AND RELEVANCE This meta-analysis of unselected, population-based studies showed a greater than 2-fold increased rate of cancer among patients with pediatric-onset IBD compared with the general pediatric populations, primarily owing to an increased rate of gastrointestinal cancers.
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Affiliation(s)
- Rahma Elmahdi
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Camilla E. Lemser
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Sandra B. Thomsen
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Kristine H. Allin
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Manasi Agrawal
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York
| | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Copenhagen, Denmark
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17
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Vanhelst J, Béghin L, Turck D, Labreuche J, Coopman S, Gottrand F, Ley D. Daily physical activity patterns in children and adolescents with inflammatory bowel disease. Pediatr Res 2021; 90:847-852. [PMID: 33469176 DOI: 10.1038/s41390-020-01313-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 11/14/2020] [Accepted: 11/19/2020] [Indexed: 01/30/2023]
Abstract
BACKGROUND The aim of this study was to assess PA patterns among children and adolescents with inflammatory bowel disease (IBD). METHODS Sixty participants with IBD (42 Crohn's disease [CD], 10 ulcerative colitis [UC], and 8 IBD-unclassified [IBD-U], 30 male patients) in remission (n = 45) or with mild disease (n = 15) were compared with 60 healthy age- and sex-matched controls. Each participant wore a triaxial accelerometer during 4 consecutive days for objective daily PA quantification. RESULTS Overall, there was no significant difference in daily PA patterns between patients with IBD and healthy controls, with 31.7% of patients with IBD and 38.3% of healthy controls fulfilling the recommendation of 60 min of moderate-to-vigorous physical activity (MVPA) daily (NS). Male patients with IBD spent significantly less time in MVPA compared with matched healthy controls (mean difference, 16.2 min day-1; p < 0.05). No difference was observed for female patients with IBD. No difference in sedentary pattern between male patients with IBD and controls was found. CONCLUSIONS Children and adolescents with inactive or mildly active IBD have similar PA patterns compared with healthy controls, except for male patients who have reduced moderate-to-vigorous PA. By far, most patients with IBD do not fulfill the MVPA recommendations for health benefits. IMPACT There is few data on PA patterns in pediatric patients with IBD. Methodological issues to assess PA limit the strengths of these studies. Pediatric IBD patients with inactive or mildly active IBD have similar physical activity patterns compared with healthy controls, except for male patients who have reduced moderate-to-vigorous PA. Most patients with IBD do not fulfill the MVPA recommendations for health benefits.
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Affiliation(s)
- Jérémy Vanhelst
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France. .,CIC 1403 - Clinical Investigation Center, CHU Lille, 59000, Lille, France.
| | - Laurent Béghin
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.,CIC 1403 - Clinical Investigation Center, CHU Lille, 59000, Lille, France
| | - Dominique Turck
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000, Lille, France
| | - Julien Labreuche
- Univ. Lille, CHU Lille, ULR 2694 - METRICS: Evaluation des technologies de santé et des pratiques médicales, 59000, Lille, France
| | - Stéphanie Coopman
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000, Lille, France
| | - Frédéric Gottrand
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000, Lille, France
| | - Delphine Ley
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000, Lille, France
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18
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Abstract
Data on long-term natural history of microscopic colitis (MC), including collagenous (CC) and lymphocytic colitis (LC), are lacking.
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19
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Roberts SE, Thorne K, Thapar N, Broekaert I, Benninga MA, Dolinsek J, Mas E, Miele E, Orel R, Pienar C, Ribes-Koninckx C, Thomson M, Tzivinikos C, Morrison-Rees S, John A, Williams JG. A Systematic Review and Meta-analysis of Paediatric Inflammatory Bowel Disease Incidence and Prevalence Across Europe. J Crohns Colitis 2020; 14:1119-1148. [PMID: 32115645 DOI: 10.1093/ecco-jcc/jjaa037] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease [IBD] is often one of the most devastating and debilitating chronic gastrointestinal disorders in children and adolescents. The main objectives here were to systematically review the incidence and prevalence of paediatric IBD across all 51 European states. METHODS We undertook a systematic review and meta-analysis based on PubMed, CINAHL, the Cochrane Library, searches of reference lists, grey literature and websites, covering the period from 1970 to 2018. RESULTS Incidence rates for both paediatric Crohn's disease [CD] and ulcerative colitis [UC] were higher in northern Europe than in other European regions. There have been large increases in the incidence of both paediatric CD and UC over the last 50 years, which appear widespread across Europe. The largest increases for CD have been reported from Sweden, Wales, England, the Czech Republic, Denmark and Hungary, and for UC from the Czech Republic, Ireland, Sweden and Hungary. Incidence rates for paediatric CD have increased up to 9 or 10 per 100 000 population in parts of Europe, including Scandinavia, while rates for paediatric UC are often slightly lower than for CD. Prevalence reported for CD ranged from 8.2 per 100 000 to approximately 60 and, for UC, from 8.3 to approximately 30. CONCLUSIONS The incidence of paediatric IBD continues to increase throughout Europe. There is stronger evidence of a north-south than an east-west gradient in incidence across Europe. Further prospective studies are needed, preferably multinational and based on IBD registries, using standardized definitions, methodology and timescales.
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Affiliation(s)
- S E Roberts
- Medical School, Swansea University, Swansea, Wales, UK
| | - K Thorne
- Medical School, Swansea University, Swansea, Wales, UK
| | - N Thapar
- Neurogastroenterology and Motility Unit, Department of Gastroenterology, Great Ormond Street Hospital, London, UK
- Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, UK
- Prince Abdullah Ben Khalid Celiac Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
| | - I Broekaert
- Department of Paediatrics, University Children's Hospital, University of Cologne, Cologne, Germany
| | - M A Benninga
- Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands
| | - J Dolinsek
- Department of Pediatrics, University Medical Center Maribor, Maribor, Slovenia
| | - E Mas
- Unité de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires, du Métabolisme, Hôpital des Enfants, CHU de Toulouse, Toulouse, France
- IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France
| | - E Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples 'Federico II', Naples, Italy
| | - R Orel
- Department of Gastroenterology, Hepatology and Nutrition, Children's Hospital, University Medical Centre, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - C Pienar
- Department of Pediatrics, 'Victor Babes' University of Medicine and Pharmacy, Timisoara, Romania
| | - C Ribes-Koninckx
- Department of Paediatric Gastroenterology, Hepatology & Nutrition, La FE University Hospital, Valencia, Spain
| | - M Thomson
- Centre for Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, UK
| | - C Tzivinikos
- Department of Paediatric Gastroenterology, Al Jalila Children's Specialty Hospital, Dubai, UAE
| | | | - A John
- Medical School, Swansea University, Swansea, Wales, UK
| | - J G Williams
- Medical School, Swansea University, Swansea, Wales, UK
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20
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Danielou M, Sarter H, Pariente B, Fumery M, Ley D, Mamona C, Barthoulot M, Charpentier C, Siproudhis L, Savoye G, Gower-Rousseau C, Andre JM, Antonietti M, Aouakli A, Armand A, Aroichane I, Assi F, Aubet JP, Auxenfants E, Ayafi-Ramelot F, Azzouzi K, Bankovski D, Barbry B, Bardoux N, Baron P, Baudet A, Bazin B, Bebahani A, Becqwort JP, Benet V, Benali H, Benguigui C, Ben Soussan E, Bental A, Berkelmans I, Bernet J, Bernou K, Bernou-Dron C, Bertot P, Bertiaux-Vandaële N, Bertrand V, Billoud E, Biron N, Bismuth B, Bleuet M, Blondel F, Blondin V, Bohon P, Boniface E, Bonnière P, Bonvarlet E, Bonvarlet P, Boruchowicz A, Bostvironnois R, Boualit M, Bouche B, Boudaillez C, Bourgeaux C, Bourgeois M, Bourguet A, Bourienne A, Branche J, Bray G, Brazier F, Breban P, Bridenne M, Brihier H, Brung-Lefebvre V, Bulois P, Burgiere P, Butel J, Canva JY, Canva-Delcambre V, Capron JP, Cardot F, Carpentier P, Cartier E, Cassar JF, Cassagnou M, Castex JF, Catala P, Cattan S, Catteau S, Caujolle B, Cayron G, Chandelier C, Chantre M, Charles J, Charneau T, Chavance-Thelu M, Chirita D, Choteau A, Claerbout JF, Clergue PY, Coevoet H, Cohen G, Collet R, Colombel JF, Coopman S, Corvisart J, et alDanielou M, Sarter H, Pariente B, Fumery M, Ley D, Mamona C, Barthoulot M, Charpentier C, Siproudhis L, Savoye G, Gower-Rousseau C, Andre JM, Antonietti M, Aouakli A, Armand A, Aroichane I, Assi F, Aubet JP, Auxenfants E, Ayafi-Ramelot F, Azzouzi K, Bankovski D, Barbry B, Bardoux N, Baron P, Baudet A, Bazin B, Bebahani A, Becqwort JP, Benet V, Benali H, Benguigui C, Ben Soussan E, Bental A, Berkelmans I, Bernet J, Bernou K, Bernou-Dron C, Bertot P, Bertiaux-Vandaële N, Bertrand V, Billoud E, Biron N, Bismuth B, Bleuet M, Blondel F, Blondin V, Bohon P, Boniface E, Bonnière P, Bonvarlet E, Bonvarlet P, Boruchowicz A, Bostvironnois R, Boualit M, Bouche B, Boudaillez C, Bourgeaux C, Bourgeois M, Bourguet A, Bourienne A, Branche J, Bray G, Brazier F, Breban P, Bridenne M, Brihier H, Brung-Lefebvre V, Bulois P, Burgiere P, Butel J, Canva JY, Canva-Delcambre V, Capron JP, Cardot F, Carpentier P, Cartier E, Cassar JF, Cassagnou M, Castex JF, Catala P, Cattan S, Catteau S, Caujolle B, Cayron G, Chandelier C, Chantre M, Charles J, Charneau T, Chavance-Thelu M, Chirita D, Choteau A, Claerbout JF, Clergue PY, Coevoet H, Cohen G, Collet R, Colombel JF, Coopman S, Corvisart J, Cortot A, Couttenier F, Crinquette JF, Crombe V, Dadamessi I, Dapvril V, Davion T, Dautreme S, Debas J, Degrave N, Dehont F, Delatre C, Delcenserie R, Delette O, Delgrange T, Delhoustal L, Delmotte JS, Demmane S, Deregnaucourt G, Descombes P, Desechalliers JP, Desmet P, Desreumaux P, Desseaux G, Desurmont P, Devienne A, Devouge E, Devred M, Devroux A, Dewailly A, Dharancy S, Di Fiore A, Djeddi D, Djedir R, Dreher-Duwat ML, Dubois R, Dubuque C, Ducatillon P, Duclay J, Ducrocq B, Ducrot F, Ducrotte P, Dufilho A, Duhamel C, Dujardin D, Dumant-Forest C, Dupas JL, Dupont F, Duranton Y, Duriez A, El Achkar K, El Farisi M, Elie C, Elie-Legrand MC, Elkhaki A, Eoche M, Evrard D, Evrard JP, Fatome A, Filoche B, Finet L, Flahaut M, Flamme C, Foissey D, Fournier P, Foutrein-Comes MC, Foutrein P, Fremond D, Frere T, Fumery M, Gallet P, Gamblin C, Ganga S, Gerard R, Geslin G, Gheyssens Y, Ghossini N, Ghrib S, Gilbert T, Gillet B, Godard D, Godard P, Godchaux JM, Godchaux R, Goegebeur G, Goria O, Gottrand F, Gower P, Grandmaison B, Groux M, Guedon C, Guillard JF, Guillem L, Guillemot F, Guimberd D, Haddouche B, Hakim S, Hanon D, Hautefeuille V, Heckestweiller P, Hecquet G, Hedde JP, Hellal H, Henneresse PE, Heyman B, Heraud M, Herve S, Hochain P, Houssin-Bailly L, Houcke P, Huguenin B, Iobagiu S, Ivanovic A, Iwanicki-Caron I, Janicki E, Jarry M, Jeu J, Joly JP, Jonas C, Katherin F, Kerleveo A, Khachfe A, Kiriakos A, Kiriakos J, Klein O, Kohut M, Kornhauser R, Koutsomanis D, Laberenne JE, Laffineur G, Lagarde M, Lalanne A, Lannoy P, Lapchin J, Laprand M, Laude D, Leblanc R, Lecieux P, Leclerc N, Le Couteulx C, Ledent J, Lefebvre J, Lefiliatre P, Legrand C, Le Grix A, Lelong P, Leluyer B, Lenaerts C, Lepileur L, Leplat A, Lepoutre-Dujardin E, Leroi H, Leroy MY, Lesage JP, Lesage X, Lesage J, Lescanne-Darchis I, Lescut J, Lescut D, Leurent B, Levy P, Lhermie M, Lion A, Lisambert B, Loire F, Louf S, Louvet A, Luciani M, Lucidarme D, Lugand J, Macaigne O, Maetz D, Maillard D, Mancheron H, Manolache O, Marks-Brunel AB, Marti R, Martin F, Martin G, Marzloff E, Mathurin P, Mauillon J, Maunoury V, Maupas JL, Mesnard B, Metayer P, Methari L, Meurisse B, Meurisse F, Michaud L, Mirmaran X, Modaine P, Monthe A, Morel L, Mortier PE, Moulin E, Mouterde O, Mudry J, Nachury M, N’Guyen Khac E, Notteghem B, Ollevier V, Ostyn A, Ouraghi A, Ouvry D, Paillot B, Panien-Claudot N, Paoletti C, Papazian A, Parent B, Pariente B, Paris JC, Patrier P, Paupart L, Pauwels B, Pauwels M, Petit R, Piat M, Piotte S, Plane C, Plouvier B, Pollet E, Pommelet P, Pop D, Pordes C, Pouchain G, Prades P, Prevost A, Prevost JC, Quesnel B, Queuniet AM, Quinton JF, Rabache A, Rabelle P, Raclot G, Ratajczyk S, Rault D, Razemon V, Reix N, Revillon M, Richez C, Robinson P, Rodriguez J, Roger J, Roux JM, Rudelli A, Saber A, Savoye G, Schlosseberg P, Segrestin M, Seguy D, Serin M, Seryer A, Sevenet F, Shekh N, Silvie J, Simon V, Spyckerelle C, Talbodec N, Techy A, Thelu JL, Thevenin A, Thiebault H, Thomas J, Thorel JM, Tielman G, Tode M, Toisin J, Tonnel J, Touchais JY, Touze Y, Tranvouez JL, Triplet C, Turck D, Uhlen S, Vaillant E, Valmage C, Vanco D, Vandamme H, Vanderbecq E, Vander Eecken E, Vandermolen P, Vandevenne P, Vandeville L, Vandewalle A, Vandewalle C, Vaneslander P, Vanhoove JP, Vanrenterghem A, Varlet P, Vasies I, Verbiese G, Vernier-Massouille G, Vermelle P, Verne C, Vezilier-Cocq P, Vigneron B, Vincendet M, Viot J, Voiment YM, Wacrenier A, Waeghemaecker L, Wallez JY, Wantiez M, Wartel F, Weber J, Willocquet JL, Wizla N, Wolschies E, Zalar A, Zaouri B, Zellweger A, Ziade C. Natural History of Perianal Fistulising Lesions in Patients With Elderly-onset Crohn's Disease: A Population-based Study. J Crohns Colitis 2020; 14:501-507. [PMID: 31637413 DOI: 10.1093/ecco-jcc/jjz173] [Show More Authors] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Most studies of elderly-onset Crohn's disease [CD; diagnosed in patients aged 60 or over] have described a mild course. However, data on the natural history of perianal fistulising CD [pfCD] in this population are scarce. In a population-based cohort study, we described the prevalence, natural history, and treatment of pfCD in patients with elderly-onset CD vs patients with paediatric-onset CD. METHOD All patients diagnosed with CD at or after the age of 60 between 1988 and 2006, were included [n = 372]. Logistic regression, Cox models, and a nested case-control method were used to identify factors associated with pfCD. RESULTS A total of 34 elderly patients [9% of the 372] had pfCD at diagnosis. After a median follow-up of 6 years (interquartile range [IQR]: 3; 10), 59 patients [16%] had pfCD; the same prevalence [16%] was observed in paediatric-onset patients. At last follow-up, anal incontinence was more frequent in elderly patients with pfCD than in elderly patients without pfCD [22% vs 4%, respectively; p < 10-4]. Rectal CD at diagnosis was associated with pfCD: hazard ratio (95% confidence interval [CI] = 2.8 [1.6-5.0]). Although 37% of the patients received immunosuppressants and 17% received anti-tumour necrosis factor agents, 24% [14 out of 59] had a definitive stoma at last follow-up. CONCLUSION During the first 6 years of disease, the prevalence of pfCD was similar in elderly and paediatric patients. Rectal involvement was associated with the appearance of pfCD in elderly-onset patients. Around a quarter of patients with elderly-onset CD will have a stoma. Our results suggest that treatment with biologics should be evaluated in these patients.
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Affiliation(s)
- Marie Danielou
- Gastroenterology Unit, EPIMAD Registry, University of Rouen and Rouen University Hospital, Rouen, France
| | - Hélène Sarter
- Public Health, Epidemiology and Economic Health Unit, EPIMAD Registry, Maison Régionale de la Recherche Clinique, University of Lille and Lille University Hospital, Lille, France.,LIRIC UMR 995, Team 5, INSERM and University of Lille, Lille, France
| | - Benjamin Pariente
- Gastroenterology Unit, EPIMAD Registry, Hôpital Huriez, Lille University Hospital, Lille, France
| | - Mathurin Fumery
- Gastroenterology Unit, EPIMAD Registry, and PeriTox, UMR I-01, University of Amiens and Amiens University Hospital, Amiens, France
| | - Delphine Ley
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Jeanne de Flandre Children's Hospital and University of Lille, Lille, France
| | - Christel Mamona
- Public Health, Epidemiology and Economic Health Unit, EPIMAD Registry, Maison Régionale de la Recherche Clinique, University of Lille and Lille University Hospital, Lille, France
| | - Maël Barthoulot
- Public Health, Epidemiology and Economic Health Unit, EPIMAD Registry, Maison Régionale de la Recherche Clinique, University of Lille and Lille University Hospital, Lille, France
| | - Cloé Charpentier
- Gastroenterology Unit, EPIMAD Registry, University of Rouen and Rouen University Hospital, Rouen, France
| | | | - Guillaume Savoye
- Gastroenterology Unit, EPIMAD Registry, University of Rouen and Rouen University Hospital, Rouen, France
| | - Corinne Gower-Rousseau
- Public Health, Epidemiology and Economic Health Unit, EPIMAD Registry, Maison Régionale de la Recherche Clinique, University of Lille and Lille University Hospital, Lille, France.,LIRIC UMR 995, Team 5, INSERM and University of Lille, Lille, France
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21
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Armstrong A, Paul C, Puig L, Boehncke WH, Freeman M, Torii H, Papp K, Griffiths CEM, Blauvelt A, Reich K, Gooderham M, Terui T, Renda L, Agada N, Xu W, Gallo G, Lebwohl MG. Safety of Ixekizumab Treatment for up to 5 Years in Adult Patients with Moderate-to-Severe Psoriasis: Results from Greater Than 17,000 Patient-Years of Exposure. Dermatol Ther (Heidelb) 2020; 10:133-150. [PMID: 31749092 PMCID: PMC6994584 DOI: 10.1007/s13555-019-00340-3] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of ixekizumab therapy in patients with psoriasis. METHODS Integrated safety data were analyzed from 13 ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies. RESULTS Total ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had ≥ 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2-7.0/100 p-y); serious infections (range 1.3-1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to 0.2/100 p-y in years 4-5); other malignancies (range 0.4-0.6/100 p-y); inflammatory bowel disease including ulcerative colitis and Crohn's disease (IR 0.2/100 p-y); and major adverse cardiovascular events (MACE) (range 0.3-0.7/100 p-y). Candidiasis was reported in 327 patients (IR 1.9/100 p-y), with the majority identified as mucocutaneous. The rate of injection site reactions was 15.5/100 p-y during year 1 and 2.0-2.3/100 p-y by years 3-5. CONCLUSIONS The decrease in rates of TEAEs and the stable rates of SAEs, other malignancies and MACE during up to 5 years of ixekizumab dosing are consistent with previous reports describing a favorable safety profile of ixekizumab following shorter durations of exposure. FUNDING Eli Lilly and Company.
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Affiliation(s)
- April Armstrong
- Department of Clinical Research, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
| | - Carle Paul
- Dermatology Department, Toulouse University Hospital (CHU), Paul Sabatier University, Toulouse, France
| | - Luis Puig
- Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Wolf Henning Boehncke
- Division of Dermatology and Venereology, Geneva University Hospitals, Geneva, Switzerland
- Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland
| | | | - Hideshi Torii
- Division of Dermatology, Tokyo Yamate Medical Center, Tokyo, Japan
| | - Kim Papp
- K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada
| | - Christopher E M Griffiths
- Dermatology Centre, Salford Royal Hospital, University of Manchester, NIHR Manchester Biomedical Research Centre, Manchester, UK
| | | | - Kristian Reich
- Center for Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Skinflammation® Center, Hamburg, Germany
| | - Melinda Gooderham
- Centre for Dermatology and Probity Medical Research, Peterborough, ON, Canada
| | - Tadashi Terui
- Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Lisa Renda
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Noah Agada
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Wen Xu
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Gaia Gallo
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Mark G Lebwohl
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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22
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Dougados M, Wei JCC, Landewé R, Sieper J, Baraliakos X, Van den Bosch F, Maksymowych WP, Ermann J, Walsh JA, Tomita T, Deodhar A, van der Heijde D, Li X, Zhao F, Bertram CC, Gallo G, Carlier H, Gensler LS. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis 2020; 79:176-185. [PMID: 31685553 PMCID: PMC7025731 DOI: 10.1136/annrheumdis-2019-216118] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 10/03/2019] [Accepted: 10/05/2019] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W). METHODS Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52. RESULTS In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks. CONCLUSION The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab. TRIAL REGISTRATION NUMBER NCT02696785/NCT02696798.
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Affiliation(s)
- Maxime Dougados
- Paris Descartes University; Department of Rheumatology, Hôpital Cochin; Assistance Publique - Hôpitaux de Paris; INSERM (U1153), Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University; Department of Internal Medicine, Chung Shan Medical University Hospital; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
| | - Robert Landewé
- Amsterdam Rheumatology and Clinical Immunology Center, Amsterdam, The Netherlands
| | | | | | | | | | - Joerg Ermann
- Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Jessica A Walsh
- Division of Rheumatology, University of Utah and Salt Lake City Veterans Affairs Medical Centers, Salt Lake City, Utah, USA
| | - Tetsuya Tomita
- Department of Orthopaedic Biomaterial Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Atul Deodhar
- Oregon Health and Science University, Portland, Oregon, USA
| | | | - Xiaoqi Li
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | - Fangyi Zhao
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | | | - Gaia Gallo
- Eli Lilly and Company, Indianapolis, Indiana, USA
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23
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Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis. Arthritis Res Ther 2020; 22:14. [PMID: 31964419 PMCID: PMC6975022 DOI: 10.1186/s13075-020-2099-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 01/09/2020] [Indexed: 02/08/2023] Open
Abstract
Background The long-term safety was assessed in patients with psoriatic arthritis who were treated with ixekizumab in three clinical trials (SPIRIT-P1/-P2/-P3). Methods Integrated safety data from three trials (controlled and uncontrolled), including two pivotal phase 3, randomized, double-blind clinical trials: SPIRIT-P1 and SPIRIT-P2, were assessed. Safety data were integrated from the all ixekizumab exposure safety population (defined as all patients receiving ≥ 1 dose of ixekizumab). We report exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at 1-year intervals up to 3 years for adverse events. Results Total exposure to IXE reached 1822.2 PY (1118 patients). The IRs/100 PY for the following treatment discontinuations were as follows: adverse events (5.3); serious infections (1.3); injection-site reactions (12.7); infections (34.2); and deaths (0.3). The IRs for treatment-emergent adverse events decreased or remained stable over time, the most common being upper respiratory tract infection, nasopharyngitis, and injection-site reactions. The IRs for serious adverse events and serious infections remained stable over time, whereas for injection-site reactions and general infections, IRs decreased with longer ixekizumab exposure. Opportunistic infections were limited to oral and esophageal candida and localized herpes zoster. No suicide or self-injury-related behaviors were reported. The IRs/100 PY for safety topics of special interest included inflammatory bowel disease (adjudicated; 0.1), depression (1.6), malignancies (0.7), and major adverse cardiovascular events (0.6). Conclusions The findings of this integrated safety analysis in patients with psoriatic arthritis are consistent with the known safety profile of ixekizumab. No unexpected safety signals were observed with ixekizumab treatment in patients with psoriatic arthritis. Trial registration SPIRIT-P1 (NCT01695239; Registered August 08, 2012), SPIRIT-P2 (NCT02349295; September 23, 2014), and SPIRIT-P3 (NCT02584855; August 04, 2015).
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24
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Mease PJ, Smolen JS, Behrens F, Nash P, Liu Leage S, Li L, Tahir H, Gooderham M, Krishnan E, Liu-Seifert H, Emery P, Pillai SG, Helliwell PS. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann Rheum Dis 2020; 79:123-131. [PMID: 31563894 PMCID: PMC6937408 DOI: 10.1136/annrheumdis-2019-215386] [Citation(s) in RCA: 209] [Impact Index Per Article: 41.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 07/23/2019] [Accepted: 08/29/2019] [Indexed: 12/19/2022]
Abstract
OBJECTIVES To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs). METHODS Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24. RESULTS The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients. CONCLUSIONS IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.
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Affiliation(s)
- Philip J Mease
- Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, Washington, USA
| | - Josef S Smolen
- Department of Medicine 3, Medical University of Vienna, Vienna, Austria
| | - Frank Behrens
- Rheumatology and Fraunhofer IME - Translational Medicine and Pharmacology, Goethe University, Frankfurt, Germany
| | - Peter Nash
- University of Queensland, Brisbane, Queensland, Australia
| | | | - Lingnan Li
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | | | | | | | | | - Paul Emery
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | - Philip S Helliwell
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
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25
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Genin M, Fumery M, Occelli F, Savoye G, Pariente B, Dauchet L, Giovannelli J, Vignal C, Body-Malapel M, Sarter H, Gower-Rousseau C, Ficheur G. Fine-scale geographical distribution and ecological risk factors for Crohn's disease in France (2007-2014). Aliment Pharmacol Ther 2020; 51:139-148. [PMID: 31588597 DOI: 10.1111/apt.15512] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 07/14/2019] [Accepted: 09/09/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Geographical variations in Crohn's disease (CD) suggest that the environment has a role in the pathogenesis of this condition. AIMS To describe the spatial distribution and the clustering of CD cases in France, and to assess the relationship between the prevalence of CD and environmental risk factors. METHODS We identified all patients with CD included in the French hospital discharge database from 2007 to 2014. Age- and gender-smoothed standardised prevalence ratios over this period were computed for 5610 spatial units. An ecological regression analysis was used to assess the relationship between the risk of CD and ecological variables (health care, latitude, socio-economic deprivation, urbanisation, proportion of agricultural surfaces and density of industries). Local spatial clusters of high-CD prevalence were searched for using elliptic spatial scan statistics and characterised in a hierarchical ascendant classification based on the same ecological variables. RESULTS About 129 089 patients with CD were identified, yielding a crude prevalence of 203 per 100 000 inhabitants. The overall spatial heterogeneity was statistically significant (P < .001). An elevated risk of CD was found to be significantly associated with high-social deprivation (relative risk [95% confidence interval] = 1.05 [1.02-1.08]) and high urbanisation (1.09 [1.04-1.14]). Sixteen significant spatial clusters of high-CD prevalence were identified; there were no common ecological variables. CONCLUSIONS The geographical distribution of CD prevalence in France is not uniform, and is associated with high levels of social deprivation and urbanisation. Larger ecological databases integrating more detailed environmental and clinical information are needed.
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Affiliation(s)
- Michaël Genin
- EA2694 - Santé Publique: épidémiologie et qualité des soins, University of Lille, Lille, France.,Department of Methodology and Biostatistics, Maison régionale de la Recherche Clinique, CHU Lille, Lille, France
| | - Mathurin Fumery
- Gastroenterology Unit, Epimad Registry, Amiens University Hospital, Amiens, France
| | - Florent Occelli
- EA 4483, Faculté de Pharmacie de Lille, Université Lille Nord de France, Lille, France
| | - Guillaume Savoye
- Gastroenterology Unit, Epimad Registry, Rouen University Hospital, Rouen, France
| | - Benjamin Pariente
- Gastroenterology Unit, Epimad Registry, Lille University Hospital, Lille, France
| | - Luc Dauchet
- Univ. Lille , U116 7 - RID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France
| | - Jonathan Giovannelli
- Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison régionale de la Recherche Clinique, Lille University Hospital, Lille, France
| | - Cécile Vignal
- Inserm, LIRIC UMR 995, Lille University, Lille, France
| | | | - Hélène Sarter
- Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison régionale de la Recherche Clinique, Lille University Hospital, Lille, France.,Inserm, LIRIC UMR 995, Lille University, Lille, France
| | - Corinne Gower-Rousseau
- Public Health, Epidemiology and Economic Health Unit, Epimad Registry, Maison régionale de la Recherche Clinique, Lille University Hospital, Lille, France.,Inserm, LIRIC UMR 995, Lille University, Lille, France
| | - Grégoire Ficheur
- EA2694 - Santé Publique: épidémiologie et qualité des soins, University of Lille, Lille, France.,Department of Methodology and Biostatistics, Maison régionale de la Recherche Clinique, CHU Lille, Lille, France
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26
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Ghaly S, Hart PH, Lawrance IC. Inflammatory bowel diseases: interrelationships between dietary vitamin D, exposure to UV radiation and the fecal microbiome. Expert Rev Gastroenterol Hepatol 2019; 13:1039-1048. [PMID: 31657973 DOI: 10.1080/17474124.2019.1685874] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Introduction: Environmental factors and an altered fecal microbiome are believed to be central to the pathogenesis of inflammatory bowel diseases (IBD). Vitamin D and ultraviolet radiation (UVR) are environmental factors that are associated by several pathways, including changes to the gastrointestinal microbiome, with the development and course of IBD.Area covered: This review explores the interaction of vitamin D, and UVR, with the intestinal innate and adaptive immune systems, and how they may influence the gut microbiome and the subsequent development, and progression, of IBD.Expert opinion: Vitamin D and UVR both regulate innate and adaptive immunity through a combination of common and independent mechanisms, with the overall effect being the promotion of immune tolerance. Vitamin D, and to a lesser extent UVR, can modify the gastrointestinal microbiome either directly, or through immune-mediated mechanisms and this may explain the effect on intestinal inflammation in animal models of IBD and some clinical studies. Thus, both vitamin D and UVR exposure can be considered potential 'master regulators' of gastrointestinal immunity, fine-tuning the complex interaction between genetics, host immunity and the gut microbiome. Further research and increased understanding of environment-host interactions is essential to achieving the ultimate goal of preventing and curing IBD.
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Affiliation(s)
- Simon Ghaly
- Department of Gastroenterology, St Vincent's Hospital, Sydney, Australia.,St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia.,Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.,Inflammation, Telethon Kids Institute, Nedlands, Australia
| | - Prue H Hart
- Inflammation, Telethon Kids Institute, Nedlands, Australia
| | - Ian C Lawrance
- Inflammation, Telethon Kids Institute, Nedlands, Australia.,Centre for Inflammatory Bowel Disease, St John of God Hospital, Subiaco, Australia
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27
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Agin M, Yucel A, Gumus M, Yuksekkaya HA, Tumgor G. The Effect of Enteral Nutrition Support Rich in TGF-β in the Treatment of Inflammatory Bowel Disease in Childhood. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:620. [PMID: 31546703 PMCID: PMC6843769 DOI: 10.3390/medicina55100620] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/16/2019] [Accepted: 09/18/2019] [Indexed: 01/07/2023]
Abstract
Background and Objective: Malnutrition is a major complication of inflammatory bowel disease (IBD). Our aim of the study was to examine the effects of Modulen IBD supplementation, which was administered to IBD patients without limiting their daily diet in addition to medical treatment, on the clinical, laboratory, anthropometric values, and disease activities of these patients. Materials and Methods: Seventy three children with IBD were evaluated retrospectively. The cases were classified as those who had Crohn disease receiving (CD-M; n = 16) or not receiving Modulen IBD (CD; n = 19) and those who had ulcerative colitis receiving (UC-M; n = 13) or not receiving Modulen IBD (UC; n = 25). Disease activities, laboratory values, remission rates, and anthropometric measurements of the groups were compared. In addition to IBD treatment, Modulen IBD in which half of the daily calorie requirement was provided was given for eight weeks. Results: In the third month of treatment, 14 (88%) patients were in remission in CD-M group and eight (42%) patients were in remission in CD group. The height and weight z scores, which were low at the time of diagnosis, improved in the first week in CD-M group. Inflammatory parameters (UC) were significantly lower in the UC-M group compared to the UC group in first and third months. In the third month, eight (62%) patients in the UC-M group and four (16%) in the UC group were remitted clinically and in terms of laboratory values. Conclusions: TGF-β-rich enteral nutrition support in children with IBD is an easy, effective, and reliable approach. It was shown that TGF-β-rich enteral nutritional supplementation enabled the disease to enter the remission earlier, and contributed to the early recovery of weight and height scores.
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Affiliation(s)
- Mehmet Agin
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Cukurova University Medical Faculty, Saricam, 01380 Adana, Turkey.
| | - Aylin Yucel
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Necmettin Erbakan University Medical Faculty, Meram, 42080 Konya, Turkey.
| | - Meltem Gumus
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Necmettin Erbakan University Medical Faculty, Meram, 42080 Konya, Turkey.
| | - Hasan Ali Yuksekkaya
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Necmettin Erbakan University Medical Faculty, Meram, 42080 Konya, Turkey.
| | - Gokhan Tumgor
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Cukurova University Medical Faculty, Saricam, 01380 Adana, Turkey.
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28
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Long-term outcome of pediatric-onset Crohn's disease: A population-based cohort study. Dig Liver Dis 2019; 51:496-502. [PMID: 30611597 DOI: 10.1016/j.dld.2018.11.033] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 11/23/2018] [Accepted: 11/26/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pediatric-onset Crohn's disease (CD) may represent a more severe form of disease. The aim of this study was to describe long-term outcome and identify associated risk factors of complicated behavior in a large population-based pediatric-onset CD cohort. PATIENTS AND METHODS Cases included all patients recorded in the EPIMAD registry diagnosed with definite or probable CD between January 1988 and December 2004, under the age of 17 years at the time of diagnosis, with at least two years of follow-up. RESULTS Five hundred and thirty-five patients were included. Median follow-up was 11.1 years [IQR, 7.3-15.0]. At the end of follow-up, 8% (n = 44) of patients had pure ileal disease (L1), 8% (n = 44) had pure colonic disease (L2), and 83% (n = 439) had ileocolonic disease (L3). L4 disease and perianal disease were observed in 42% (n = 227) and 16% (n = 85) of patients, respectively. At the end of follow-up, 58% (n = 308) of patients presented complicated disease behavior (B2, 39% and B3, 19%), and 42% (n = 163) of patients with inflammatory behavior at diagnosis had evolved to complicated behavior. During follow-up, 86% of patients (n = 466) received at least one course of corticosteroids, 67% (n = 357) of patients had been exposed to immunosuppressants and 35% (n = 187) of patients received at least one anti-TNF agent. Forty-three percent (n = 230) of patients underwent at least one intestinal resection. The overall mortality rate was 0.93% and the SMR was 1.6 [0.5-3.8] (p = 0.20). Five cancers were reported with a crude cancer incidence rate of 1.1% and an SIR of 3.3 [1.2-7.0] (p = 0.01). In a multivariate Cox model, ileal (HR, 1.87 [1.09-3.21], p = 0.022) or ileocolonic (HR, 1.54 [1.01-2.34], p = 0.042) and perianal lesions at diagnosis (HR, 1.81 [1.13- 2.89], p = 0.013) were significantly associated with complicated behavior. CONCLUSION About 80% of patients with pediatric-onset CD presented extensive ileocolonic disease during follow-up. The majority of patients evolved to complicated behavior. Surgery, cancer and mortality were observed in 43%, 0.9% and 0.9% of patients, respectively.
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A Novel Rare Missense Variation of the NOD2 Gene: Evidencesof Implication in Crohn's Disease. Int J Mol Sci 2019; 20:ijms20040835. [PMID: 30769939 PMCID: PMC6412783 DOI: 10.3390/ijms20040835] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 01/23/2019] [Accepted: 02/03/2019] [Indexed: 11/17/2022] Open
Abstract
The NOD2 gene, involved in innate immune responses to bacterial peptidoglycan, has been found to be closely associated with Crohn’s Disease (CD), with an Odds Ratio ranging from 3–36. Families with three or more CD-affected members were related to a high frequency of NOD2 gene variations, such as R702W, G908R, and 1007fs, and were reported in the EPIMAD Registry. However, some rare CD multiplex families were described without identification of common NOD2 linked-to-disease variations. In order to identify new genetic variation(s) closely linked with CD, whole exome sequencing was performed on available subjects, comprising four patients in two generations affected with Crohn’s disease without R702W and G908R variation and three unaffected related subjects. A rare and, not yet, reported missense variation of the NOD2 gene, N1010K, was detected and co-segregated across affected patients. In silico evaluation and modelling highlighted evidence for an adverse effect of the N1010K variation with regard to CD. Moreover, cumulative characterization of N1010K and 1007fs as a compound heterozygous state in two, more severe CD family members strongly suggests that N1010K could well be a new risk factor involved in Crohn’s disease genetic susceptibility.
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Egeberg A, Thyssen JP, Burisch J, Colombel JF. Incidence and Risk of Inflammatory Bowel Disease in Patients with Psoriasis—A Nationwide 20-Year Cohort Study. J Invest Dermatol 2019; 139:316-323. [DOI: 10.1016/j.jid.2018.07.029] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 07/24/2018] [Accepted: 07/25/2018] [Indexed: 12/20/2022]
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Duricova D, Sarter H, Savoye G, Leroyer A, Pariente B, Armengol-Debeir L, Bouguen G, Ley D, Turck D, Templier C, Buche S, Peyrin-Biroulet L, Gower-Rousseau C, Fumery M. Impact of Extra-Intestinal Manifestations at Diagnosis on Disease Outcome in Pediatric- and Elderly-Onset Crohn's Disease: A French Population-Based Study. Inflamm Bowel Dis 2019; 25:394-402. [PMID: 30085159 DOI: 10.1093/ibd/izy254] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Extraintestinal manifestations (EIM) have been associated with more severe course of inflammatory bowel disease. The aim was to study the frequency of EIM in pediatric- and elderly-onset Crohn's disease (CD) and the factors associated with EIM and their impact on long-term disease outcome. METHODS Pediatric- (age at diagnosis younger than 17 years) and elderly-onset CD patients (age at diagnosis 60 years or older) from a prospective population-based registry (EPIMAD) were recruited. Data on EIM and clinical factors at diagnosis and at maximal follow-up were collected. RESULTS We included 535 pediatric- and 370 elderly-onset patients (median age 14.5 and 69.9 years; median follow-up 11.1 and 5.9 years). Extraintestinal manifestations presented in 23.5% of childhood-onset and 4.9% of elderly-onset individuals at diagnosis, while in 29.8% and 5.9% of patients, EIM developed newly during the follow-up (hazard ration [HR] 4.4, 95% CI, 2.7-7.0, P < 0.001). The most frequently involved organ in both age cohorts, either at diagnosis or during disease course, were joints (pediatric: 11.2% and 22.6%; elderly: 3.2% and 3.5%, respectively) followed by skin (pediatric: 15.9% and 13.6%; elderly: 2.7% and 2.7%, respectively). Extraintestinal manifestations at diagnosis were associated with increased risk for corticosteroids (HR 1.42, 95% CI, 1.14-1.78 and HR 3.38, 95% CI, 1.88-6.08) and immunosuppressive therapy (HR 1.30, 95% CI, 1.02-1.65 and HR 4.24, 95% CI, 1.91-9.42), in both age populations. CONCLUSIONS Extraintestinal manifestations occurred at lower frequency in elderly-onset compared with pediatric-onset patients. In both age populations, presence of EIM at diagnosis independently increased the need for corticosteroid and immunosuppressive treatment.
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Affiliation(s)
- Dana Duricova
- Public Health, Epidemiology and Economic Health, Register Epimad, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France.,IBD clinical and research centre, ISCARE, Prague, Czech Republic
| | - Hélène Sarter
- Public Health, Epidemiology and Economic Health, Register Epimad, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France.,Lille Inflammation Research International Centre LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - Guillaume Savoye
- Gastroenterology Unit, Epimad Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
| | - Ariane Leroyer
- Public Health, Epidemiology and Economic Health, Register Epimad, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France
| | - Benjamin Pariente
- Gastroenterology Unit, Hôpital Huriez, Lille University Hospital, Lille, France
| | - Laura Armengol-Debeir
- Gastroenterology Unit, Epimad Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
| | | | - Delphine Ley
- Lille Inflammation Research International Centre LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, University of Lille, Lille, France
| | - Dominique Turck
- Lille Inflammation Research International Centre LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, University of Lille, Lille, France
| | - Carole Templier
- Dermatology Unit, Hôpital Huriez, Lille University Hospital, Lille, France
| | - Sebastien Buche
- Dermatology Unit, Hôpital Huriez, Lille University Hospital, Lille, France
| | | | - Corinne Gower-Rousseau
- Public Health, Epidemiology and Economic Health, Register Epimad, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France.,Lille Inflammation Research International Centre LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - Mathurin Fumery
- Lille Inflammation Research International Centre LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France.,Gastroenterology Unit, Epimad Registry, CHU Amiens Sud, l, Amiens University Hospital, Amiens, France
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Duricova D, Pariente B, Sarter H, Fumery M, Leroyer A, Charpentier C, Armengol-Debeir L, Peyrin-Biroulet L, Savoye G, Gower-Rousseau C. Impact of age at diagnosis on natural history of patients with elderly-onset ulcerative colitis: A French population-based study. Dig Liver Dis 2018; 50:903-909. [PMID: 29739650 DOI: 10.1016/j.dld.2018.04.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2017] [Revised: 04/04/2018] [Accepted: 04/10/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Recent population-based study of elderly-onset Crohn's disease patients reported age-related differences in disease phenotype and outcome. AIMS The aim was to assess the impact of age at diagnosis on natural history of elderly-onset ulcerative colitis patients with emphasis on disease presentation, phenotype and treatment. METHODS Elderly-onset patients with ulcerative colitis (≥60 years at diagnosis) registered in a French population-based Registry EPIMAD (1988-2006) were included. Demographic and clinical data at diagnosis and at maximal follow-up were collected using predefined questionnaire. RESULTS Four-hundred and sixty-five elderly-onset ulcerative colitis patients were included (median follow-up 6.2 years); 276 (59%) were <70 and 189 (41%) ≥70 years at diagnosis. Patients aged <70 years presented with more rectal bleeding (86% vs. 79%, p = .06) and abdominal pain (44% vs. 34%, p = .04) while those ≥70 years had higher rate of left-sided colitis (62% vs. 49%; p = .02). Cumulative exposure to 5-ASA, corticosteroids and immunosuppressants was similar between the groups as well as surgery rate. However, patients <70 years were significantly more steroid-resistant than older individuals (12% vs. 3%, p < .05) while no significant difference in steroid-dependency was observed. CONCLUSION Patients with elderly-onset ulcerative colitis differed in presentation, disease phenotype and response to medication with respect to age at diagnosis.
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Affiliation(s)
- Dana Duricova
- Public Health, Epidemiology and Economic Health, Epimad Registry, Hospital & University Centre of Clinical Research, Lille University and Hospital, France; IBD Clinical and Research Centre, ISCARE I.V.F., a.s., Charles University, Prague
| | - Benjamin Pariente
- Gastroenterology Unit, Hôpital Huriez, Lille University Hospital, France
| | - Hélène Sarter
- Public Health, Epidemiology and Economic Health, Epimad Registry, Hospital & University Centre of Clinical Research, Lille University and Hospital, France; Lille Inflammation Research International Center LIRIC-UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - Mathurin Fumery
- Gastroenterology Unit, Epimad Registry, CHU Amiens Sud, Amiens University Hospital, France; Lille Inflammation Research International Center LIRIC-UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - Ariane Leroyer
- Public Health, Epidemiology and Economic Health, Epimad Registry, Hospital & University Centre of Clinical Research, Lille University and Hospital, France
| | - Cloe Charpentier
- Gastroenterology Unit, Epimad Registry, Charles Nicolle Hospital, Rouen University Hospital, France
| | - Laura Armengol-Debeir
- Gastroenterology Unit, Epimad Registry, Charles Nicolle Hospital, Rouen University Hospital, France
| | | | - Guillaume Savoye
- Gastroenterology Unit, Epimad Registry, Charles Nicolle Hospital, Rouen University Hospital, France
| | - Corinne Gower-Rousseau
- Public Health, Epidemiology and Economic Health, Epimad Registry, Hospital & University Centre of Clinical Research, Lille University and Hospital, France; Lille Inflammation Research International Center LIRIC-UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France.
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Ghaly S, Kaakoush NO, Lloyd F, Gordon L, Forest C, Lawrance IC, Hart PH. Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of Vitamin D in Mice. Nutrients 2018; 10:nu10081069. [PMID: 30103486 PMCID: PMC6116187 DOI: 10.3390/nu10081069] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 08/02/2018] [Accepted: 08/06/2018] [Indexed: 01/01/2023] Open
Abstract
Reduced sunlight exposure has been associated with an increased incidence of Crohn’s disease and ulcerative colitis. The effect of ultraviolet radiation (UVR) on the faecal microbiome and susceptibility to colitis has not been explored. C57Bl/6 female mice were fed three different vitamin D-containing diets for 24 days before half of the mice in each group were UV-irradiated (1 kJ/m2) for each of four days, followed by twice-weekly irradiation of shaved dorsal skin for 35 days. Faecal DNA was extracted and high-throughput sequencing of the 16S RNA gene performed. UV irradiation of skin was associated with a significant change in the beta-diversity of faeces compared to nonirradiated mice, independently of vitamin D. Specifically, members of phylum Firmicutes, including Coprococcus, were enriched, whereas members of phylum Bacteroidetes, such as Bacteroidales, were depleted. Expression of colonic CYP27B1 increased by four-fold and IL1β decreased by five-fold, suggesting a UVR-induced anti-inflammatory effect. UV-irradiated mice, however, were not protected against colitis induced by dextran sodium sulfate (DSS), although distinct faecal microbiome differences were documented post-DSS between UV-irradiated and nonirradiated mice. Thus, skin exposure to UVR alters the faecal microbiome, and further investigations to explore the implications of this in health and disease are warranted.
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Affiliation(s)
- Simon Ghaly
- Telethon Kids Institute, The University of Western Australia, Perth, WA 6008, Australia.
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6009, Australia.
- Department of Gastroenterology and Hepatology, St. Vincent's Hospital, Sydney, NSW 2010, Australia.
| | - Nadeem O Kaakoush
- School of Medical Sciences, UNSW Sydney, Kensington, NSW 2033, Australia.
| | - Frances Lloyd
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6009, Australia.
| | - Lavinia Gordon
- Australian Genome Research Facility, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia.
| | - Cynthia Forest
- Department of Anatomical Pathology, PathWest, Fiona Stanley Hospital, Murdoch, WA 6150, Australia.
| | - Ian C Lawrance
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6009, Australia.
- Centre for Inflammatory Bowel Disease, St. John of God Hospital, Subiaco, WA 6008, Australia.
| | - Prue H Hart
- Telethon Kids Institute, The University of Western Australia, Perth, WA 6008, Australia.
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Sacleux SC, Sarter H, Fumery M, Charpentier C, Guillon-Dellac N, Coevoet H, Pariente B, Peyrin-Biroulet L, Gower-Rousseau C, Savoye G. Post-operative complications in elderly onset inflammatory bowel disease: a population-based study. Aliment Pharmacol Ther 2018; 47:1652-1660. [PMID: 29737553 DOI: 10.1111/apt.14790] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 08/06/2017] [Accepted: 04/08/2018] [Indexed: 12/29/2022]
Abstract
BACKGROUND IBD diagnosed after the age of 60 is increasing. Data on post-operative complications in elderly onset IBD are scarce. AIM To describe the incidence of and factors associated with post-operative complications in elderly onset IBD, diagnosed after the age of 60. METHODS Using EPIMAD Cohort (1988-2006), among 841 incident IBD patients, 139 (17%) underwent intestinal surgery, including 100 Crohn's disease (CD) and 39 ulcerative colitis (UC). RESULTS After a median post-operative follow-up of 6 years (2-10), 50 (36%) patients experienced at least 1 complication with a total of 69. During the first 30 post-operative days, the mortality rate was 4%. Thirty-two early complications (<30 days) were observed in 23 patients (17%), with 15 infectious, without significant difference between CD and UC. More than half early post-operative complications (n = 19, 59%) were severe (>grade 2) without significant difference between CD and UC (P = 0.28). Thirty-seven long-term adverse effects of surgical therapy (≥30 days) were observed in 33 patients (24%). Multivariate analysis found (1) acute severe colitis (OR = 7.84 [2.15-28.52]) and emergency surgery (OR = 4.46 [1.75-11.36]) were associated with early post-operative complications, and (2) Female gender (HR = 2.10 [1.01-4.37]) and delay before surgery >3 months (HR = 2.09 [1.01-4.31]) with long-term adverse effects of surgical therapy. CONCLUSIONS One-third of elderly IBD patients experienced at least 1 post-operative complication. Half of the early complications were severe, and infectious. Emergency surgery was the key driver for post-operative complication.
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Affiliation(s)
- S-C Sacleux
- Epimad Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
| | - H Sarter
- Public Health, Epidemiology and Economic Health, Epimad Registry, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France.,Lille Inflammation Research International Center LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - M Fumery
- Epimad Registry, CHU Amiens Sud, Avenue Laennec-Salouel, Amiens University Hospital, Amiens, France
| | - C Charpentier
- Epimad Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
| | - N Guillon-Dellac
- Public Health, Epidemiology and Economic Health, Epimad Registry, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France.,Lille Inflammation Research International Center LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - H Coevoet
- Clinique des Bonnettes, Arras, France
| | - B Pariente
- Hôpital Huriez, Lille University Hospital, Lille, France
| | | | - C Gower-Rousseau
- Public Health, Epidemiology and Economic Health, Epimad Registry, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France.,Lille Inflammation Research International Center LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - G Savoye
- Epimad Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
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The treatment of refractory ulcerative colitis. Best Pract Res Clin Gastroenterol 2018; 32-33:49-57. [PMID: 30060939 DOI: 10.1016/j.bpg.2018.05.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 04/25/2018] [Accepted: 05/10/2018] [Indexed: 02/08/2023]
Abstract
Ulcerative proctitis is defined as a mucosal inflammation limited to the rectum. Ulcerative proctitis is responsible for distressing symptoms and alteration of patient quality of life. Effective treatment is important to prevent or delay proximal extension of the disease and to improve quality of life. Refractory ulcerative proctitis is defined as the failure of topical and oral 5-aminosalicylic acid and corticosteroids. Medical management of refractory ulcerative proctitis may be challenging as there is little evidence regarding drug efficacy in this clinical situation. Data are currently available for azathioprine, topical tacrolimus and anti-TNF monoclonal antibodies as rescue treatment for refractory ulcerative proctitis. Other biologics may be of benefit despite a lack of dedicated clinical trials. Ultimately, experimental therapies such as epidermal growth factor enemas, appendectomy or fecal transplantation may be tried before restorative proctocolectomy with J pouch anastomosis, which has demonstrated good results with regards to clinical remission and quality of life.
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Ghione S, Sarter H, Fumery M, Armengol-Debeir L, Savoye G, Ley D, Spyckerelle C, Pariente B, Peyrin-Biroulet L, Turck D, Gower-Rousseau C, Andre JM, Antonietti M, Aouakli A, Armand A, Aroichane I, Assi F, Aubet JP, Auxenfants E, Ayafi-Ramelot F, Bankovski D, Barbry B, Bardoux N, Baron P, Baudet A, Bazin B, Bebahani A, Becqwort JP, Benet V, Benali H, Benguigui C, Soussan BE, Bental A, Berkelmans I, Bernet J, Bernou K, Bernou-Dron C, Bertot P, Bertiaux-Vandaële N, Bertrand V, Billoud E, Biron N, Bismuth B, Bleuet M, Blondel F, Blondin V, Bohon P, Boniface E, Bonnière P, Bonvarlet E, Bonvarlet P, Boruchowicz A, Bostvironnois R, Boualit M, Bouche B, Boudaillez C, Bourgeaux C, Bourgeois M, Bourguet A, Bourienne A, Branche J, Bray G, Brazier F, Breban P, Brihier H, Brung-Lefebvre V, Bulois P, Burgiere P, Butel J, Canva JY, Canva-Delcambre V, Capron JP, Cardot F, Carpentier P, Cartier E, Cassar JF, Cassagnou M, Castex JF, Catala P, Cattan S, Catteau S, Caujolle B, Cayron G, Chandelier C, Chantre M, Charles J, Charneau T, Chavance-Thelu M, Chirita D, Choteau A, Claerbout JF, Clergue PY, Coevoet H, Cohen G, Collet R, Colombel JF, Coopman S, Corvisart J, Cortot A, Couttenier F, et alGhione S, Sarter H, Fumery M, Armengol-Debeir L, Savoye G, Ley D, Spyckerelle C, Pariente B, Peyrin-Biroulet L, Turck D, Gower-Rousseau C, Andre JM, Antonietti M, Aouakli A, Armand A, Aroichane I, Assi F, Aubet JP, Auxenfants E, Ayafi-Ramelot F, Bankovski D, Barbry B, Bardoux N, Baron P, Baudet A, Bazin B, Bebahani A, Becqwort JP, Benet V, Benali H, Benguigui C, Soussan BE, Bental A, Berkelmans I, Bernet J, Bernou K, Bernou-Dron C, Bertot P, Bertiaux-Vandaële N, Bertrand V, Billoud E, Biron N, Bismuth B, Bleuet M, Blondel F, Blondin V, Bohon P, Boniface E, Bonnière P, Bonvarlet E, Bonvarlet P, Boruchowicz A, Bostvironnois R, Boualit M, Bouche B, Boudaillez C, Bourgeaux C, Bourgeois M, Bourguet A, Bourienne A, Branche J, Bray G, Brazier F, Breban P, Brihier H, Brung-Lefebvre V, Bulois P, Burgiere P, Butel J, Canva JY, Canva-Delcambre V, Capron JP, Cardot F, Carpentier P, Cartier E, Cassar JF, Cassagnou M, Castex JF, Catala P, Cattan S, Catteau S, Caujolle B, Cayron G, Chandelier C, Chantre M, Charles J, Charneau T, Chavance-Thelu M, Chirita D, Choteau A, Claerbout JF, Clergue PY, Coevoet H, Cohen G, Collet R, Colombel JF, Coopman S, Corvisart J, Cortot A, Couttenier F, Crinquette JF, Crombe V, Dadamessi I, Dapvril V, Davion T, Dautreme S, Debas J, Degrave N, Dehont F, Delatre C, Delcenserie R, Delette O, Delgrange T, Delhoustal L, Delmotte JS, Demmane S, Deregnaucourt G, Descombes P, Desechalliers JP, Desmet P, Desreumaux P, Desseaux G, Desurmont P, Devienne A, Devouge E, Devred M, Devroux A, Dewailly A, Dharancy S, Di Fiore A, Djeddi D, Djedir R, Dreher-Duwat ML, Dubois R, Dubuque C, Ducatillon P, Duclay J, Ducrocq B, Ducrot F, Ducrotte P, Dufilho A, Duhamel C, Dujardin D, Dumant-Forest C, Dupas JL, Dupont F, Duranton Y, Duriez A, El Achkar K, El Farisi M, Elie C, Elie-Legrand MC, Elkhaki A, Eoche M, Evrard D, Evrard JP, Fatome A, Filoche B, Finet L, Flahaut M, Flamme C, Foissey D, Fournier P, Foutrein-Comes MC, Foutrein P, Fremond D, Frere T, Fumery M, Gallet P, Gamblin C, Ganga-Zandzou PS, Gérard R, Geslin G, Gheyssens Y, Ghossini N, Ghrib S, Gilbert T, Gillet B, Godard D, Godard P, Godchaux JM, Godchaux R, Goegebeur G, Goria O, Gottrand F, Gower P, Grandmaison B, Groux M, Guedon C, Guillard JF, Guillem L, Guillemot F, Guimber D, Haddouche B, Hakim S, Hanon D, Hautefeuille V, Heckestweiller P, Hecquet G, Hedde JP, Hellal H, Henneresse PE, Heyman B, Heraud M, Herve S, Hochain P, Houssin-Bailly L, Houcke P, Huguenin B, Iobagiu S, Ivanovic A, Iwanicki-Caron I, Janicki E, Jarry M, Jeu J, Joly JP, Jonas C, Katherin F, Kerleveo A, Khachfe A, Kiriakos A, Kiriakos J, Klein O, Kohut M, Kornhauser R, Koutsomanis D, Laberenne JE, Laffineur G, Lagarde M, Lannoy P, Lapchin J, Lapprand M, Laude D, Leblanc R, Lecieux P, Leclerc N, Le Couteulx C, Ledent J, Lefebvre J, Lefiliatre P, Legrand C, Le Grix A, Lelong P, Leluyer B, Lenaerts C, Lepileur L, Leplat A, Lepoutre-Dujardin E, Leroi H, Leroy MY, Lesage JP, Lesage X, Lesage J, Lescanne-Darchis I, Lescut J, Lescut D, Leurent B, Levy P, Lhermie M, Lion A, Lisambert B, Loire F, Louf S, Louvet A, Luciani M, Lucidarme D, Lugand J, Macaigne O, Maetz D, Maillard D, Mancheron H, Manolache O, Marks-Brunel AB, Marti R, Martin F, Martin G, Marzloff E, Mathurin P, Mauillon J, Maunoury V, Maupas JL, Mesnard B, Metayer P, Methari L, Meurisse B, Meurisse F, Michaud L, Mirmaran X, Modaine P, Monthe A, Morel L, Mortier PE, Moulin E, Mouterde O, Mudry J, Nachury M, Khac NE, Notteghem B, Ollevier V, Ostyn A, Ouraghi A, Ouvry D, Paillot B, Panien-Claudot N, Paoletti C, Papazian A, Parent B, Pariente B, Paris JC, Patrier P, Paupart L, Pauwels B, Pauwels M, Petit R, Piat M, Piotte S, Plane C, Plouvier B, Pollet E, Pommelet P, Pop D, Pordes C, Pouchain G, Prades P, Prevost A, Prevost JC, Quesnel B, Queuniet AM, Quinton JF, Rabache A, Rabelle P, Raclot G, Ratajczyk S, Rault D, Razemon V, Reix N, Revillon M, Richez C, Robinson P, Rodriguez J, Roger J, Roux JM, Rudelli A, Saber A, Savoye G, Schlosseberg P, Segrestin M, Seguy D, Serin M, Seryer A, Sevenet F, Shekh N, Silvie J, Simon V, Spyckerelle C, Talbodec N, Techy A, Thelu JL, Thevenin A, Thiebault H, Thomas J, Thorel JM, Tielman G, Tode M, Toisin J, Tonnel J, Touchais JY, Touze Y, Tranvouez JL, Triplet C, Turck D, Uhlen S, Vaillant E, Valmage C, Vanco D, Vandamme H, Vanderbecq E, Eecken VE, Vandermolen P, Vandevenne P, Vandeville L, Vandewalle A, Vandewalle C, Vaneslander P, Vanhoove JP, Vanrenterghem A, Varlet P, Vasies I, Verbiese G, Vernier-Massouille G, Vermelle P, Verne C, Vezilier-Cocq P, Vigneron B, Vincendet M, Viot J, Voiment YM, Wacrenier A, Waeghemaecker L, Wallez JY, Wantiez M, Wartel F, Weber J, Willocquet JL, Wizla N, Wolschies E, Zalar A, Zaouri B, Zellweger A, Ziade C. Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents. Am J Gastroenterol 2018; 113:265-272. [PMID: 28809388 DOI: 10.1038/ajg.2017.228] [Show More Authors] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 06/08/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. METHODS Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. RESULTS 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/105 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/105 (+126%; P<0.001) and for UC, from 1.6 to 4.1/105 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. CONCLUSIONS In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.
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Affiliation(s)
- Silvia Ghione
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital and Faculty of Medicine, Lille, France
| | - Hélène Sarter
- Public Health, Epidemiology and Economic Health, Epimad registry, Regional house of clinical research, Lille Hospital and University, Lille, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm-"IBD and environmental factors: epidemiology and functional analyses", Lille University, Lille, France
| | - Mathurin Fumery
- Gastroenterology Unit, Epimad registry, Amiens Hospital and University, Amiens, France
| | - Laura Armengol-Debeir
- Gastroenterology Unit, Epimad registry, Rouen Hospital and University, Rouen, France
| | - Guillaume Savoye
- Gastroenterology Unit, Epimad registry, Rouen Hospital and University, Rouen, France
| | - Delphine Ley
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital and Faculty of Medicine, Lille, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm-"IBD and environmental factors: epidemiology and functional analyses", Lille University, Lille, France
| | - Claire Spyckerelle
- Department of Pediatrics, St Vincent de Paul Hospital and Lille Catholic University, Lille, France
| | - Benjamin Pariente
- Lille Inflammation Research International Center LIRIC-UMR 995 Inserm-"IBD and environmental factors: epidemiology and functional analyses", Lille University, Lille, France.,Gastroenterology Unit, Epimad registry, Lille Hospital and University, Lille, France
| | | | - Dominique Turck
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital and Faculty of Medicine, Lille, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm-"IBD and environmental factors: epidemiology and functional analyses", Lille University, Lille, France
| | - Corinne Gower-Rousseau
- Public Health, Epidemiology and Economic Health, Epimad registry, Regional house of clinical research, Lille Hospital and University, Lille, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm-"IBD and environmental factors: epidemiology and functional analyses", Lille University, Lille, France
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Hochart A, Gower-Rousseau C, Sarter H, Fumery M, Ley D, Spyckerelle C, Peyrin-Biroulet L, Laberenne JE, Vasseur F, Savoye G, Turck D. Ulcerative proctitis is a frequent location of paediatric-onset UC and not a minor disease: a population-based study. Gut 2017; 66:1912-1917. [PMID: 27489240 DOI: 10.1136/gutjnl-2016-311970] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 06/29/2016] [Accepted: 07/14/2016] [Indexed: 12/08/2022]
Abstract
OBJECTIVE Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC. PATIENTS AND METHODS All patients with UC diagnosed <17 years from 1988 to 2004, and followed during >2 years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models. RESULTS 158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5 years (Q1: 11.4-Q3: 16.1) have been identified and followed during a median of 11.4 years (8.2-15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1 year, 45% at 5 years and 52% at 10 years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13% at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2-E3-E4 group. CONCLUSIONS UP is frequent in paediatric-onset UC and should not be considered as a minor disease. Compared with more extensive UC locations, risks for colonic extension, anti-TNF-α therapy and colectomy were similar in UP, whereas the risk for use of IM was lower.
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Affiliation(s)
- A Hochart
- Gastroenterology, Hepatology and Nutrition Unit, Department of Pediatrics, Lille University and Hospital, France et Univ. Lille CHU Lille, Lille, France
| | - C Gower-Rousseau
- Lille Inflammation Research International Center LIRIC-UMR 995 Team 5, Inserm/Université Lille 2/CHRU de Lille, Lille, France.,Public Health, Epidemiology and Economic Health, Registre Epimad, Maison Régionale de la Recherche Clinique, Centre Hospitalier Universitaire Régional, Lille, Cedex, France
| | - H Sarter
- Lille Inflammation Research International Center LIRIC-UMR 995 Team 5, Inserm/Université Lille 2/CHRU de Lille, Lille, France.,Public Health, Epidemiology and Economic Health, Registre Epimad, Maison Régionale de la Recherche Clinique, Centre Hospitalier Universitaire Régional, Lille, Cedex, France
| | - M Fumery
- Lille Inflammation Research International Center LIRIC-UMR 995 Team 5, Inserm/Université Lille 2/CHRU de Lille, Lille, France.,Gastroenterology Unit, Epimad Registry, CHU Amiens Sud, Avenue Laennec-Salouel, Amiens University Hospital, France
| | - D Ley
- Gastroenterology, Hepatology and Nutrition Unit, Department of Pediatrics, Lille University and Hospital, France et Univ. Lille CHU Lille, Lille, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Team 5, Inserm/Université Lille 2/CHRU de Lille, Lille, France
| | - C Spyckerelle
- Gastroenterology, Hepatology and Nutrition Unit, Department of Pediatrics, Saint Vincent de Paul Hospital and Lille Catholic University, Lille, France
| | - L Peyrin-Biroulet
- Hepato-Gastroenterology Unit, Inserm, U954, Nancy University Hospital, France
| | - J-E Laberenne
- Hepato-Gastroenterology Unit, Epimad Registry, General Hospital, Seclin, France
| | - F Vasseur
- Department of Biostatistics, EA 2694, Lille University Hospital, France
| | - G Savoye
- Gastroenterology Unit, Epimad Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
| | - D Turck
- Gastroenterology, Hepatology and Nutrition Unit, Department of Pediatrics, Lille University and Hospital, France et Univ. Lille CHU Lille, Lille, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Team 5, Inserm/Université Lille 2/CHRU de Lille, Lille, France
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Hager CL, Ghannoum MA. The mycobiome: Role in health and disease, and as a potential probiotic target in gastrointestinal disease. Dig Liver Dis 2017; 49:1171-1176. [PMID: 28988727 DOI: 10.1016/j.dld.2017.08.025] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 07/27/2017] [Accepted: 08/07/2017] [Indexed: 12/11/2022]
Abstract
The human gastrointestinal (GI) tract is home to trillions of microorganisms, some beneficial and others potentially harmful. Recent advances in science have allowed us to identify the multitude of organisms inhabiting the GI tract and parse out those that play a role in inflammatory bowel disease (IBD). Unfortunately, most research has focused on studying only the bacteria while ,overlooking a key player, fungus. In order to address this issue, we have focused our efforts on studying the fungal community in the GI tract known as the mycobiome. We found that patients with Crohn's disease (CD) tend to have much higher levels of the fungus Candida tropicalis compared to their healthy family members, as well as two bacteria, Escherichia coli and Serratia marcescens. Furthermore, we showed that these three organisms worked together to form robust biofilms capable of exacerbating intestinal inflammation. Herein, we discuss the role of the mycobiome in health and disease, and highlight the importance of maintaining balance of the GI microbiota. Additionally, taking into consideration recent next generation sequencing data, we provide insight into potentially new therapeutic approaches in the treatment of IBD through the use of antifungals and/or probiotics aimed at establishing and maintaining a healthy balance of the GI total microbial community including fungi and bacteria.
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Affiliation(s)
- Christopher L Hager
- Center for Medical Mycology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Mahmoud A Ghannoum
- Center for Medical Mycology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, United States.
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Duricova D, Leroyer A, Savoye G, Sarter H, Pariente B, Aoucheta D, Armengol-Debeir L, Ley D, Turck D, Peyrin-Biroulet L, Gower-Rousseau C, Fumery M, Antonietti M, Aouakli A, Armand A, Aroichane I, Assi F, Aubet JP, Auxenfants E, Ayafi-Ramelot F, Bankovski D, Barbry B, Bardoux N, Baron P, Baudet A, Bazin B, Bebahani A, Becqwort JP, Benet V, Benali H, Benguigui C, Ben Soussan E, Bental A, Berkelmans I, Bernet J, Bernou K, Bernou-Dron C, Bertot P, Bertiaux-Vandaële N, Bertrand V, Billoud E, Biron N, Bismuth B, Bleuet M, Blondel F, Blondin V, Bohon P, Boniface E, Bonnière P, Bonvarlet E, Bonvarlet P, Boruchowicz A, Bostvironnois R, Boualit M, Bouche B, Boudaillez C, Bourgeaux C, Bourgeois M, Bourguet A, Bourienne A, Branche J, Bray G, Brazier F, Breban P, Brihier H, Brung-Lefebvre V, Bulois P, Burgiere P, Butel J, Canva JY, Canva-Delcambre V, Capron JP, Cardot F, Carpentier P, Cartier E, Cassar JF, Cassagnou M, Castex JF, Catala P, Cattan S, Catteau S, Caujolle B, Cayron G, Chandelier C, Chantre M, Charles J, Charneau T, Chavance-Thelu M, Chirita D, Choteau A, Claerbout JF, Clergue PY, Coevoet H, Cohen G, Collet R, Colombel JF, Coopman S, Corvisart J, Cortot A, Couttenier F, et alDuricova D, Leroyer A, Savoye G, Sarter H, Pariente B, Aoucheta D, Armengol-Debeir L, Ley D, Turck D, Peyrin-Biroulet L, Gower-Rousseau C, Fumery M, Antonietti M, Aouakli A, Armand A, Aroichane I, Assi F, Aubet JP, Auxenfants E, Ayafi-Ramelot F, Bankovski D, Barbry B, Bardoux N, Baron P, Baudet A, Bazin B, Bebahani A, Becqwort JP, Benet V, Benali H, Benguigui C, Ben Soussan E, Bental A, Berkelmans I, Bernet J, Bernou K, Bernou-Dron C, Bertot P, Bertiaux-Vandaële N, Bertrand V, Billoud E, Biron N, Bismuth B, Bleuet M, Blondel F, Blondin V, Bohon P, Boniface E, Bonnière P, Bonvarlet E, Bonvarlet P, Boruchowicz A, Bostvironnois R, Boualit M, Bouche B, Boudaillez C, Bourgeaux C, Bourgeois M, Bourguet A, Bourienne A, Branche J, Bray G, Brazier F, Breban P, Brihier H, Brung-Lefebvre V, Bulois P, Burgiere P, Butel J, Canva JY, Canva-Delcambre V, Capron JP, Cardot F, Carpentier P, Cartier E, Cassar JF, Cassagnou M, Castex JF, Catala P, Cattan S, Catteau S, Caujolle B, Cayron G, Chandelier C, Chantre M, Charles J, Charneau T, Chavance-Thelu M, Chirita D, Choteau A, Claerbout JF, Clergue PY, Coevoet H, Cohen G, Collet R, Colombel JF, Coopman S, Corvisart J, Cortot A, Couttenier F, Crinquette JF, Crombe V, Dadamessi I, Dapvril V, Davion T, Dautreme S, Debas J, Degrave N, Dehont F, Delatre C, Delcenserie R, Delette O, Delgrange T, Delhoustal L, Delmotte JS, Demmane S, Deregnaucourt G, Descombes P, Desechalliers JP, Desmet P, Desreumaux P, Desseaux G, Desurmont P, Devienne A, Devouge E, Devred M, Devroux A, Dewailly A, Dharancy S, Di Fiore A, Djeddi D, Djedir R, Dreher-Duwat ML, Dubois R, Dubuque C, Ducatillon P, Duclay J, Ducrocq B, Ducrot F, Ducrotté P, Dufilho A, Duhamel C, Dujardin D, Dumant-Forest C, Dupas JL, Dupont F, Duranton Y, Duriez A, El Achkar K, El Farisi M, Elie C, Elie-Legrand MC, Elkhaki A, Eoche M, Evrard D, Evrard JP, Fatome A, Filoche B, Finet L, Flahaut M, Flamme C, Foissey D, Fournier P, Foutrein-Comes MC, Foutrein P, Fremond D, Frere T, Fumery M, Gallet P, Gamblin C, Ganga-Zandzou S, Gerard R, Geslin G, Gheyssens Y, Ghossini N, Ghrib S, Gilbert T, Gillet B, Godard D, Godard P, Godchaux JM, Godchaux R, Goegebeur G, Goria O, Gottrand F, Gower P, Grandmaison B, Groux M, Guedon C, Guillard JF, Guillem L, Guillemot F, Guimber D, Haddouche B, Hakim S, Hanon D, Hautefeuille V, Heckestweiller P, Hecquet G, Hedde JP, Hellal H, Henneresse PE, Heyman B, Heraud M, Herve S, Hochain P, Houssin-Bailly L, Houcke P, Huguenin B, Iobagiu S, Ivanovic A, Iwanicki-Caron I, Janicki E, Jarry M, Jeu J, Joly JP, Jonas C, Katherin F, Kerleveo A, Khachfe A, Kiriakos A, Kiriakos J, Klein O, Kohut M, Kornhauser R, Koutsomanis D, Laberenne JE, Laffineur G, Lagarde M, Lannoy P, Lapchin J, Lapprand M, Laude D, Leblanc R, Lecieux P, Leclerc N, Le Couteulx C, Ledent J, Lefebvre J, Lefiliatre P, Legrand C, Le Grix A, Lelong P, Leluyer B, Lenaerts C, Lepileur L, Leplat A, Lepoutre-Dujardin E, Leroi H, Leroy MY, Lesage JP, Lesage X, Lesage J, Lescanne-Darchis I, Lescut J, Lescut D, Leurent B, Levy P, Lhermie M, Lion A, Lisambert B, Loire F, Louf S, Louvet A, Luciani M, Lucidarme D, Lugand J, Macaigne O, Maetz D, Maillard D, Mancheron H, Manolache O, Marks-Brunel AB, Marti R, Martin F, Martin G, Marzloff E, Mathurin P, Mauillon J, Maunoury V, Maupas JL, Mesnard B, Metayer P, Methari L, Meurisse B, Meurisse F, Michaud L, Mirmaran X, Modaine P, Monthe A, Morel L, Mortier PE, Moulin E, Mouterde O, Mudry J, Nachury M, N’Guyen Khac E, Notteghem B, Ollevier V, Ostyn A, Ouraghi A, Ouvry D, Paillot B, Panien-Claudot N, Paoletti C, Papazian A, Parent B, Pariente B, Paris JC, Patrier P, Paupart L, Pauwels B, Pauwels M, Petit R, Piat M, Piotte S, Plane C, Plouvier B, Pollet E, Pommelet P, Pop D, Pordes C, Pouchain G, Prades P, Prevost A, Prevost JC, Quesnel B, Queuniet AM, Quinton JF, Rabache A, Rabelle P, Raclot G, Ratajczyk S, Rault D, Razemon V, Reix N, Revillon M, Richez C, Robinson P, Rodriguez J, Roger J, Roux JM, Rudelli A, Saber A, Savoye G, Schlosseberg P, Segrestin M, Seguy D, Serin M, Seryer A, Sevenet F, Shekh N, Silvie J, Simon V, Spyckerelle C, Talbodec N, Techy A, Thelu JL, Thevenin A, Thiebault H, Thomas J, Thorel JM, Tielman G, Tode M, Toisin J, Tonnel J, Touchais JY, Touze Y, Tranvouez JL, Triplet C, Turck D, Uhlen S, Vaillant E, Valmage C, Vanco D, Vandamme H, Vanderbecq E, Vander Eecken E, Vandermolen P, Vandevenne P, Vandeville L, Vandewalle A, Vandewalle C, Vaneslander P, Vanhoove JP, Vanrenterghem A, Varlet P, Vasies I, Verbiese G, Vernier-Massouille G, Vermelle P, Verne C, Vezilier-Cocq P, Vigneron B, Vincendet M, Viot J, Voiment YM, Wacrenier A, Waeghemaecker L, Wallez JY, Wantiez M, Wartel F, Weber J, Willocquet JL, Wizla N, Wolschies E, Zalar A, Zaouri B, Zellweger A, Ziade C. Extra-intestinal Manifestations at Diagnosis in Paediatric- and Elderly-onset Ulcerative Colitis are Associated With a More Severe Disease Outcome: A Population-based Study. J Crohns Colitis 2017; 11:1326-1334. [PMID: 28981648 DOI: 10.1093/ecco-jcc/jjx092] [Show More Authors] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 07/05/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Data on extra-intestinal manifestations [EIM] and their impact on the disease course of ulcerative colitis [UC] in population-based cohorts are scarce, particularly in paediatric- and elderly-onset UC patients. The aims of this population-based study were to assess: 1] the occurrence of EIM in paediatric- and elderly-onset UC; 2] the factors associated with EIM; and 3] their impact on long-term disease outcome. METHODS Paediatric-onset [< 17 years at diagnosis] and elderly-onset UC patients [> 60 years at diagnosis] from a French prospective population-based registry [EPIMAD] were included. Data on EIM and other clinical factors at diagnosis and at maximal follow-up were collected. RESULTS In all, 158 paediatric- and 470 elderly-onset patients were included [median age at diagnosis 14.5 and 68.8 years, median follow-up 11.2 and 6.2 years, respectively]. EIM occurred in 8.9% of childhood- and 3% of elderly-onset patients at diagnosis and in 16.7% and 2.2% of individuals during follow-up [p < 0.01], respectively. The most frequent EIM was joint involvement [15.8% of paediatric onset and 2.6% of elderly-onset]. Presence of EIM at diagnosis was associated with more severe disease course [need for immunosuppressants or biologic therapy or colectomy] in both paediatric- and elderly-onset UC (hazard ratio [HR] = 2.0, 95% confidence interval [CI]: 1.0-4.2; and HR = 2.8, 0.9-7.9, respectively). Extensive colitis was another independent risk factor in both age groups. CONCLUSIONS Elderly-onset UC patients had lower risk of EIM either at diagnosis or during follow-up than paediatric-onset individuals. EIM at diagnosis predicted more severe disease outcome, including need for immunosuppressive or biologic therapy or surgery, in both paediatric- and elderly-onset UC.
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Affiliation(s)
- Dana Duricova
- Public Health, Epidemiology and Economic Health, Registre EPIMAD, Lille University and Hospital, Lille, France
| | - Ariane Leroyer
- Public Health, Epidemiology and Economic Health, Registre EPIMAD, Lille University and Hospital, Lille, France
| | - Guillaume Savoye
- Gastroenterology Unit, EPIMAD Registry, Rouen University Hospital, Rouen, France
| | - Hélène Sarter
- Public Health, Epidemiology and Economic Health, Registre EPIMAD, Lille University and Hospital, Lille, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm Lille 2 University, Lille, France
| | - Benjamin Pariente
- Gastroenterology Unit, Hôpital Huriez, Lille University Hospital, Lille, France
| | - Djamila Aoucheta
- Associated Medical Director, Immunology, MSD France, Courbevoie cedex, France
| | | | - Delphine Ley
- Lille Inflammation Research International Center LIRIC-UMR 995 Inserm Lille 2 University, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Lille University Jeanne de Flandre Children's Hospital, University of Lille, Lille, France
| | - Dominique Turck
- Lille Inflammation Research International Center LIRIC-UMR 995 Inserm Lille 2 University, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Lille University Jeanne de Flandre Children's Hospital, University of Lille, Lille, France
| | | | - Corinne Gower-Rousseau
- Public Health, Epidemiology and Economic Health, Registre EPIMAD, Lille University and Hospital, Lille, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm Lille 2 University, Lille, France
| | - Mathurin Fumery
- Lille Inflammation Research International Center LIRIC-UMR 995 Inserm Lille 2 University, Lille, France.,Gastroenterology Unit, EPIMAD Registry, Amiens University Hospital, Amiens, France
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Fumery M, Kohut M, Gower-Rousseau C, Duhamel A, Brazier F, Thelu F, Nagorniewicz F, Lamarche F, Nguyen-Khac E, Sabbagh C, Loreau J, Colombel JF, Savoye G, Chatelain D, Dupas JL. Incidence, Clinical Presentation, and Associated Factors of Microscopic Colitis in Northern France: A Population-Based Study. Dig Dis Sci 2017; 62:1571-1579. [PMID: 27659673 DOI: 10.1007/s10620-016-4306-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 09/07/2016] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To date, there are no epidemiological data on microscopic colitis (MC) in France. The aim of this study was to determine the incidence of MC in the Somme department in Northern France, to evaluate clinical characteristics, and to search for risk factors for both collagenous colitis (CC) and lymphocytic colitis (LC). DESIGN Between January 1, 2005, and December 31, 2007, four pathology units in the Somme department recorded all new cases of MC diagnosed in patients living in the area. Colonic biopsies were reviewed by 4 pathologists together. For each incident case, demographic, clinical, endoscopic, and biological data were collected according to methodology of the EPIMAD registry. RESULTS One hundred and thirty cases of MC, including 87 CC and 43 LC, were recorded during the three-year study. The mean annual incidence for MC was 7.9/105 inhabitants, 5.3/105 inhabitants for CC, and 2.6/105 inhabitants for LC. Annual standardized incidence of Crohn's disease and ulcerative colitis in the EPIMAD registry during the same period (2005-2007) were 7.4/105 and 4.9/105, respectively. Median age at diagnosis was 63 years for MC, 70 for CC, and 48 for LC. The female-to-male gender ratio was 3.5 for MC, 4.1 for CC, and 2.6 for LC. Median time to diagnosis was 8 weeks. Chronic diarrhea and abdominal pain were, respectively, present in 93 and 47 % of the cases. An autoimmune disease was associated in 28 % of MC cases. At diagnosis, proton pump inhibitor treatment was more often reported in CC than in LC (46 vs 16 %; p = 0.003). Budesonide was effective on diarrhea in 77 % of patients, and thirteen percent of patients became steroid dependent. CONCLUSION This population-based study shows that the incidence of MC in France is high and similar to Crohn's disease incidence and confirms that this condition is associated with female gender, autoimmune diseases, and medications.
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Affiliation(s)
- Mathurin Fumery
- Service d'hepatogastroenterologie, Gastroenterology Unit, Amiens University and Hospital, Université de Picardie Jules Verne, Avenue Laennec-Salouel, 80000, Amiens, France. .,EPIMAD registry, Amiens, France.
| | - Mathieu Kohut
- Gastroenterology, St. Isabelle Clinic, Abbeville, France
| | - Corinne Gower-Rousseau
- LIRIC-UMR 995 INSERM, IBD team and Environmental Factors: Epidemiology and Functional Analyses, Lille University, Lille, France.,Public Health, Epidemiology and Economic Health, EPIMAD registry, Regional Clinical Research Center, Lille University and Hospital, Cedex, France
| | - Alain Duhamel
- Biostatistics Unit, CERIM, EA2694, Lille University and Hospital, Lille, France
| | - Franck Brazier
- Service d'hepatogastroenterologie, Gastroenterology Unit, Amiens University and Hospital, Université de Picardie Jules Verne, Avenue Laennec-Salouel, 80000, Amiens, France.,EPIMAD registry, Amiens, France
| | - Francoise Thelu
- Pathology Laboratory, 40 rue Andre Chenier, 80000, Amiens, France
| | | | - Francois Lamarche
- Pathology Laboratory, 13 Rue Sainte-Catherine, 80100, Abbeville, France
| | - Eric Nguyen-Khac
- Service d'hepatogastroenterologie, Gastroenterology Unit, Amiens University and Hospital, Université de Picardie Jules Verne, Avenue Laennec-Salouel, 80000, Amiens, France
| | - Charles Sabbagh
- Department of Digestive Surgery, Amiens University Hospital, Amiens, France
| | - Julien Loreau
- Service d'hepatogastroenterologie, Gastroenterology Unit, Amiens University and Hospital, Université de Picardie Jules Verne, Avenue Laennec-Salouel, 80000, Amiens, France
| | - Jean-Frederic Colombel
- Dr. Henry D Janowitz, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Guillaume Savoye
- Gastroenterology Unit, EPIMAD registry, Rouen University and Hospital, Rouen, France
| | - Denis Chatelain
- Pathology Unit, Amiens University and Hospital, Picardie University Jules Verne, Amiens, France
| | - Jean-Louis Dupas
- Service d'hepatogastroenterologie, Gastroenterology Unit, Amiens University and Hospital, Université de Picardie Jules Verne, Avenue Laennec-Salouel, 80000, Amiens, France.,EPIMAD registry, Amiens, France
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Affiliation(s)
- Nicole M Gentile
- Division of Gastroenterology, NorthShore University HealthSystem, University of Chicago, Pritzker School of Medicine, 2650 Ridge Avenue, Suite G221, Evanston, IL, 60201, USA
| | - Eugene F Yen
- Division of Gastroenterology, NorthShore University HealthSystem, University of Chicago, Pritzker School of Medicine, 2650 Ridge Avenue, Suite G221, Evanston, IL, 60201, USA.
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Bequet E, Sarter H, Fumery M, Vasseur F, Armengol-Debeir L, Pariente B, Ley D, Spyckerelle C, Coevoet H, Laberenne JE, Peyrin-Biroulet L, Savoye G, Turck D, Gower-Rousseau C. Incidence and Phenotype at Diagnosis of Very-early-onset Compared with Later-onset Paediatric Inflammatory Bowel Disease: A Population-based Study [1988-2011]. J Crohns Colitis 2017; 11:519-526. [PMID: 28453757 DOI: 10.1093/ecco-jcc/jjw194] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 10/26/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Very-early-onset inflammatory bowel disease [VEO-IBD] is a form of IBD that is distinct from that of children with an older onset. We compared changes over time in the incidence and phenotype at diagnosis between two groups according to age at IBD diagnosis: VEO-IBD diagnosed before the age of 6 years, and early-onset IBD [EO-IBD] diagnosed between 6 and 16 years of age. METHODS Data were obtained from a cohort enrolled in a prospective French population-based registry from 1988 to 2011. RESULTS Among the 1412 paediatric cases [< 17 years], 42 [3%] were VEO-IBD. In the VEO-IBD group, the incidence remained stable over the study period. In contrast, the incidence of EO-IBD increased from 4.4/105 in 1988-1990 to 9.5/105 in 2009-2011 [+116%; p < 10-4]. Crohn's disease [CD] was the most common IBD, regardless of age, but ulcerative colitis [UC] and unclassified IBD were more common in VEO-IBD cases [40% vs 26%; p = 0.04]. VEO-IBD diagnosis was most often performed in hospital [69% vs 43%; p < 10-3]. Rectal bleeding and mucous stools were more common in patients with VEO-IBD, whereas weight loss and abdominal pain were more frequent in those with EO-IBD. Regarding CD, isolated colonic disease was more common in the VEO-IBD group [39% vs 14%; p = 0.003]. CONCLUSIONS In this large population-based cohort, the incidence of VEO-IBD was low and stable from 1988 to 2011, with a specific clinical presentation. These results suggest a probable genetic origin for VEO-IBD, whereas the increase in EO-IBD might be linked to environmental factors.
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Affiliation(s)
- E Bequet
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Lille University Jeanne de Flandre Children's Hospital, University of Lille, Lille, France
| | - H Sarter
- Public Health, Epidemiology and Economic Health, Registre EPIMAD, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France
- Lille Inflammation Research International Center LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - M Fumery
- Gastroenterology Unit, EPIMAD Registry, CHU Amiens Sud, Amiens University Hospital, Amiens, France
| | - F Vasseur
- Biostatistics Unit, EA 2694, Lille University and Hospital, Lille, France
| | - L Armengol-Debeir
- Gastroenterology Unit, EPIMAD Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
| | - B Pariente
- Gastroenterology Unit, Hôpital Huriez, Lille University Hospital, Lille, France
| | - D Ley
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Lille University Jeanne de Flandre Children's Hospital, University of Lille, Lille, France
- Lille Inflammation Research International Center LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - C Spyckerelle
- Paediatric Unit, St Vincent Hospital, Catholic University, Lille, France
| | - H Coevoet
- Gastroenterology Unit, Les Bonnettes Private Hospital, Arras, France
| | - J E Laberenne
- Gastroenterology Unit, General Hospital, Seclin, France
| | - L Peyrin-Biroulet
- Gastroenterology Unit, Inserm U954, Université de Lorraine, Nancy, France
| | - G Savoye
- Gastroenterology Unit, EPIMAD Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
| | - D Turck
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Lille University Jeanne de Flandre Children's Hospital, University of Lille, Lille, France
- Lille Inflammation Research International Center LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
| | - C Gower-Rousseau
- Public Health, Epidemiology and Economic Health, Registre EPIMAD, Maison Régionale de la Recherche Clinique, Lille University and Hospital, Lille, France
- Lille Inflammation Research International Center LIRIC - UMR 995 Inserm Lille 2 University, CHRU de Lille, Lille, France
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Gower-Rousseau C, Sarter H, Savoye G, Tavernier N, Fumery M, Sandborn WJ, Feagan BG, Duhamel A, Guillon-Dellac N, Colombel JF, Peyrin-Biroulet L. Validation of the Inflammatory Bowel Disease Disability Index in a population-based cohort. Gut 2017; 66:588-596. [PMID: 26646934 DOI: 10.1136/gutjnl-2015-310151] [Citation(s) in RCA: 121] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Revised: 11/07/2015] [Accepted: 11/09/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND IBDs are chronic destructive disorders that negatively affect the functional status of patients. Recently, the Inflammatory Bowel Disease Disability Index (IBD-DI) was developed according to standard WHO processes. The aims of the current study were to validate the IBD-DI in an independent patient cohort, to develop an index-specific scoring system and to describe the disability status of a well-defined population-based cohort of French patients with IBD. METHODS From February 2012 to March 2014, the IBD-DI questionnaire was administered to a random sample of adult patients with an established diagnosis of IBD issued from a French population-based registry. The IBD-DI consists of 28 items that evaluate the four domains of body functions, activity participation, body structures and environmental factors. Validation included item reduction and data structure, construct validity, internal consistency, interobserver and intraobserver reliability evaluations. RESULTS 150 patients with Crohn's disease (CD) and 50 patients with UC completed the IBD-DI validation phase. The intraclass correlation coefficient for interobserver reliability was 0.91 and 0.54 for intraobserver reliability. Cronbach's α of internal consistency was 0.86. IBD-DI scores varied from 0 to 100 with a mean of 35.3 (Q1=19.6; Q3=51.8). IBD-DI scores were highly correlated with Inflammatory Bowel Disease Questionnaire (-0.82; p<0.001) and SF-36 (-0.61; p<0.05) scores. Female gender (p<0.001), clinical disease activity (p<0.0001) and disease duration (p=0.02) were associated with higher IBD-DI scores. CONCLUSIONS The IBD-DI has been validated for use in clinical trials and epidemiological studies. The IBD-DI showed high internal consistency, interobserver reliability and construct validity, and a moderate intraobserver reliability. It comprises 14 questions and ranges from 0 to 100. The mean IBD-DI score was 35.3 and was associated with gender, clinical disease activity and disease duration. Further research is needed to confirm the structural validity and to assess the responsiveness of IBD-DI. TRIAL REGISTRATION NUMBER 2011-A00877-34.
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Affiliation(s)
- Corinne Gower-Rousseau
- Public Health, Epidemiology and Economic Health, Registre Epimad, Maison Régionale de la Recherche Clinique, Centre Hospitalier Universitaire Régional, Lille Cedex, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm/Université Lille 2/CHRU de Lille; Equipe «IBD and environmental factors: epidemiology and functional analyses, Lille University, France
| | - Hélène Sarter
- Public Health, Epidemiology and Economic Health, Registre Epimad, Maison Régionale de la Recherche Clinique, Centre Hospitalier Universitaire Régional, Lille Cedex, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm/Université Lille 2/CHRU de Lille; Equipe «IBD and environmental factors: epidemiology and functional analyses, Lille University, France
| | - Guillaume Savoye
- Gastroenterology Unit, Epimad Registry, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France
| | - Noémie Tavernier
- Gastroenterology Unit, Hôpital Huriez, Lille University Hospital, France
| | - Mathurin Fumery
- Gastroenterology Unit, Epimad Registry, CHU Amiens Sud, Avenue Laennec- Salouel, Amiens University Hospital, France
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | | | - Alain Duhamel
- Univ. Lille, CHU Lille, EA 2694-Santé publique : épidémiologie et qualité des soins, Lille, France
| | - Nathalie Guillon-Dellac
- Public Health, Epidemiology and Economic Health, Registre Epimad, Maison Régionale de la Recherche Clinique, Centre Hospitalier Universitaire Régional, Lille Cedex, France.,Lille Inflammation Research International Center LIRIC-UMR 995 Inserm/Université Lille 2/CHRU de Lille; Equipe «IBD and environmental factors: epidemiology and functional analyses, Lille University, France
| | | | - Laurent Peyrin-Biroulet
- Gastroenterology Department and Inserm U954, Nancy University Hospital, Université de Lorraine, Nancy, France
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Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: A presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials. J Am Acad Dermatol 2017; 76:441-448.e2. [DOI: 10.1016/j.jaad.2016.10.027] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 10/13/2016] [Accepted: 10/16/2016] [Indexed: 02/08/2023]
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Subramanian S, Ekbom A, Rhodes JM. Recent advances in clinical practice: a systematic review of isolated colonic Crohn's disease: the third IBD? Gut 2017; 66:362-381. [PMID: 27802156 DOI: 10.1136/gutjnl-2016-312673] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 09/05/2016] [Accepted: 09/06/2016] [Indexed: 12/13/2022]
Abstract
The genetics of isolated colonic Crohn's disease place it approximately midway between Crohn's disease with small intestinal involvement and UC, making a case for considering it as a separate condition. We have therefore systematically reviewed its epidemiology, pathophysiology and treatment. Key findings include a higher incidence in females (65%) and older average age at presentation than Crohn's disease at other sites, a mucosa-associated microbiota between that found in ileal Crohn's disease and UC, no response to mesalazine, but possibly better response to antitumour necrosis factor than Crohn's disease at other sites. Diagnostic distinction from UC is often difficult and also needs to exclude other conditions including ischaemic colitis, segmental colitis associated with diverticular disease and tuberculosis. Future studies, particularly clinical trials, but also historical cohorts, should assess isolated colonic Crohn's disease separately.
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Affiliation(s)
- Sreedhar Subramanian
- Institute of Translational Medicine, University of Liverpool, The Henry Wellcome Laboratory, Liverpool, UK
| | - Anders Ekbom
- Department of Medicine, Karolinska Institute, Stockholm, Sweden
| | - Jonathan M Rhodes
- Institute of Translational Medicine, University of Liverpool, The Henry Wellcome Laboratory, Liverpool, UK
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Abstract
OBJECTIVES The respective role of disease activity and steroid therapy in growth impairment in paediatric-onset Crohn disease (CD) is still debated. Our aim was to investigate whether the growth pattern of children with CD was correlated with the inflammatory status during the disease course, regardless the cumulative duration of steroid therapy. METHODS One hundred and seven patients with a diagnosis of CD <17 years, followed during ≥2 years and for whom ≥2 height measures were available during follow-up, were identified between 1998 and 2010. Height, C-reactive protein (CRP), orosomucoid, and steroid therapy duration were collected at each visit. The relationship between the evolution of growth velocity and inflammatory status during follow-up was investigated using a linear mixed model with random coefficients. RESULTS Median age at diagnosis was 11.7 years (Q1-Q3: 9.8-13.5). Mean height for age (H/A) z score was 0.14 ± 1.29 at diagnosis and 0.05 ± 1.23 among the 75 patients who had reached their final height at maximal follow-up (median: 4.9 years; Q1-Q3: 3.8-6.4). Growth failure (H/A z score <-2) was present in 7 (8%) patients at diagnosis and 5 (5%) at maximal follow-up. Growth velocity was negatively correlated with the evolution of CRP (P < 0.0001) and orosomucoid (P < 0.0001) during follow-up. After adjustment for the cumulative duration of steroid therapy, these 2 correlations remained significant (CRP: P = 0.0008; orosomucoid: P < 0.0001). CONCLUSIONS Children with CD with uncontrolled inflammatory status have a lower growth velocity. The inflammatory status should be kept as close to normal as possible in paediatric-onset patients with CD to optimize their growth pattern.
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Cancer in Elderly Onset Inflammatory Bowel Disease: A Population-Based Study. Am J Gastroenterol 2016; 111:1428-1436. [PMID: 27481308 DOI: 10.1038/ajg.2016.304] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Accepted: 06/18/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Cancer may be a complication of inflammatory bowel disease (IBD) or its treatment. In elderly onset IBD patients the risk of malignancy is of particular concern. We studied this risk in a population-based cohort of elderly onset IBD patients. METHODS In a French population-based cohort, we identified 844 patients aged >60 years at IBD diagnosis from 1988 to 2006, including 370 Crohn's disease (CD) and 474 ulcerative colitis (UC). We compared incidence of cancer among IBD patients with that observed in the French Network of population-based Cancer Registries (FRANCIM). Confidence interval (CI) was estimated assuming a Poisson-specific law for rare events. Results were expressed using the standardized incidence ratios (SIRs) and their CI 95%. RESULTS Median age at IBD diagnosis was 70 (65-76) years in CD and 69 (64-74) in UC. Median follow-up was 6 (2-11) years for both diseases with a number of person-years of 5,598. Among the 844 elderly onset IBD cases, 98 (11.6%; 42 CD and 56 UC) developed a cancer after IBD diagnosis (67 men and 31 women) corresponding to an overall SIR of 0.97 (0.80-1.18). These cancers occurred at a median age of 77 years (71-80) and 75 years (71-81) in patients with CD and UC, respectively. Median time between IBD diagnosis and cancers was 78 months (40-121). There was no significant increased risk of colorectal cancer in IBD (SIR=1.03 (0.62-1.70), CD (SIR=1.20 (0.57-2.52) nor in UC (SIR=0.91 (0.45-1.82) without significant protective role of 5-aminosalicylic acid (hazard ratio (HR)=0.7 (0.2-2.6)). No significant risk for other intestinal cancers was found, especially for small bowel carcinoma. An increased risk of malignant lymphoproliferative disorders was found in all IBD and in CD: SIR=2.49 (1.25-4.99) and SIR=3.09 (1.16-8.23), respectively. An increased risk of myeloproliferative disorders was found in all IBD (SIR=2.18 (1.09-4.35)). Thiopurines exposure, using a time-dependant Cox model, was not found as associated with an increased risk to develop cancer, HR=0.90 (0.48-1.68). CONCLUSIONS There is no increased risk for developing intestinal cancer among patients with elderly onset IBD in this population-based cohort. There are increased risks of developing lymphoproliferative and myeloproliferative disorders in all IBD. Thiopurines exposure was not found as associated with an increased risk to lymphoproliferative disorders. These data reinforce the difference between elderly onset IBD as compared with patients with younger age at IBD onset.
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Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn's Disease. mBio 2016; 7:mBio.01250-16. [PMID: 27651359 PMCID: PMC5030358 DOI: 10.1128/mbio.01250-16] [Citation(s) in RCA: 305] [Impact Index Per Article: 33.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Crohn’s disease (CD) results from a complex interplay between host genetic factors and endogenous microbial communities. In the current study, we used Ion Torrent sequencing to characterize the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in patients with CD and their nondiseased first-degree relatives (NCDR) in 9 familial clusters living in northern France-Belgium and in healthy individuals from 4 families living in the same area (non-CD unrelated [NCDU]). Principal component, diversity, and abundance analyses were conducted, and CD-associated inter- and intrakingdom microbial correlations were determined. Significant microbial interactions were identified and validated using single- and mixed-species biofilms. CD and NCDR groups clustered together in the mycobiome but not in the bacteriome. Microbiotas of familial (CD and NCDR) samples were distinct from those of nonfamilial (NCDU) samples. The abundance of Serratia marcescens and Escherichia coli was elevated in CD patients, while that of beneficial bacteria was decreased. The abundance of the fungus Candida tropicalis was significantly higher in CD than in NCDR (P = 0.003) samples and positively correlated with levels of anti-Saccharomyces cerevisiae antibodies (ASCA). The abundance of C. tropicalis was positively correlated with S. marcescens and E. coli, suggesting that these organisms interact in the gut. The mass and thickness of triple-species (C. tropicalis plus S. marcescens plus E. coli) biofilm were significantly greater than those of single- and double-species biofilms. C. tropicalis biofilms comprised blastospores, while double- and triple-species biofilms were enriched in hyphae. S. marcescens used fimbriae to coaggregate or attach with C. tropicalis/E. coli, while E. coli was closely apposed with C. tropicalis. Specific interkingdom microbial interactions may be key determinants in CD. Here, we characterized the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in multiplex families with CD and healthy relatives and defined the microbial interactions leading to dysbiosis in CD. We identified fungal (Candida tropicalis) and bacterial (Serratia marcescens and Escherichia coli) species that are associated with CD dysbiosis. Additionally, we found that the level of anti-Saccharomyces cerevisiae antibodies (ASCA; a known CD biomarker) was associated with the abundance of C. tropicalis. We also identified positive interkingdom correlations between C. tropicalis, E. coli, and S. marcescens in CD patients and validated these correlations using in vitro biofilms. These results provide insight into the roles of bacteria and fungi in CD and may lead to the development of novel treatment approaches and diagnostic assays.
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Natural History of Crohn's Disease in Elderly Patients Diagnosed Over the Age of 70 Years: A Population-Based Study. Inflamm Bowel Dis 2016; 22:1698-707. [PMID: 27206018 DOI: 10.1097/mib.0000000000000821] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Elderly onset (>60 yrs at diagnosis) Crohn's disease (CD) seems to be associated with a better outcome than when diagnosed earlier in life. The aim of this study was to compare the natural history of patients with CD older than 70 years at diagnosis with that of elderly patients diagnosed between 60 and 70 years in the EPIMAD population-based registry. METHODS Three hundred seventy patients with elderly onset CD diagnosed between January 1988 and December 2006 were identified. Among them, 188 (63%) were older than 70 years at diagnosis (≥70 yrs). Clinical presentation, disease location, and behavior at diagnosis and also natural history, surgery needs, and drug exposure were recorded, with a median follow-up of 4.5 years (1.1; 8.3) in CD diagnosed after 70 years and of 7.8 years (3.3; 12.1) in CD diagnosed between 60 and 70 years, respectively. RESULTS CD incidence in elderly patients diagnosed ≥70 years was 2.3/100,000 inhabitants, compared with 2.6/100,000 in elderly patients diagnosed below the age of 70 (60-69 yrs). The proportion of males was lower in patients ≥70 years than in patients aged 60 to 69 (31% versus 45%, P = 0.006). Clinical presentation at diagnosis was similar in both groups. Pure colonic location (L2) was more frequent among patients >70 years both at diagnosis (73% versus 57%, P = 0.004) and maximal follow-up (70% versus 47%, P < 0.0001). Disease extension (from L1 or L2 to L3) was not significantly different among patients >70 years and patients aged 60 to 69 years (hazard ratio [HR] = 2.0 [0.9; 4.5] for 60 to 69 yrs, P = 0.09). The most frequent behavior in the 2 groups was inflammatory, both at diagnosis (75% versus 80%, P = 0.43) and at maximal follow-up (69% versus 70%, P = 0.55). There was no significant difference in patients >70 years compared with patients aged 60 to 69 years regarding treatment with 5-aminosalicylic acid (P = 0.72), oral corticosteroids (P = 0.83), and anti-tumor necrosis factor therapies (P = 0.37). However, the use of immunosuppressants was significantly less frequent in patients >70 years (HR = 2.1 [1.3; 3.5] for 60 to 69 yrs, P = 0.003). Risk of surgery was similar in both groups (P = 0.72). Extraintestinal manifestations at diagnosis were significantly associated with an evolution to complicated behavior (HR = 2.7 [1.0; 7.0], P = 0.045), immunosuppressant treatment (HR = 2.9 [1.4; 6.0], P = 0.006), and corticosteroid use (HR = 3.3 [1.8; 6.1], P < 0.0001). CONCLUSIONS The natural history of CD in elderly patients diagnosed over the age of 70 is mild with low disease extension and complicated behavior. This needs to be taken into account when establishing therapeutic strategies.
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Abstract
BACKGROUND We describe, in a population-based cohort, the incidence of and factors associated with postoperative complications (POCs) in pediatric-onset inflammatory bowel disease. METHODS Using the pediatric population-based EPIMAD Cohort (1988-2004), among 692 incident inflammatory bowel disease cases, 128 patients with Crohn's disease (CD) and 25 with ulcerative colitis (UC) (22%) had undergone at least 1 major abdominal surgery at a median age of 16 years [interquartile range, Q1-Q3 = 14-17]. Factors associated with POC were assessed using Cox models. RESULTS After a median postoperative follow-up of 8 years (3-12), 76 (49.7%) patients had experienced at least 1 POC with a total of 113 complications. The frequency of severe POC (grade >2) was similar in CD and UC (28% of all complications versus 27%, P = 0.95). A total of 64 early POCs (within 30 d of surgery) were observed in 47 patients (31%), with 33 being infectious and 31 noninfectious, higher in UC than in CD (25% of patients with CD versus 60% of patients with UC, P < 0.001). Forty-nine late POCs (≥30 d) were observed in 37 patients (24%). The occurrence of late POC was similar in UC and CD. The cumulative probability of POC was 31% (95% confidence interval, 24-39) at 1 month, 46% (38-54) at 1 year, and 48% (41-57) at 5 years. Multivariate analysis found that the UC type was the only factor associated with early POC (hazard ratio = 2.9; 95% confidence interval, 1.6-5.4). CONCLUSIONS One-half of the children with inflammatory bowel disease had experienced at least 1 POC. Only UC relative to CD was significantly associated with an increased risk of early POC.
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