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Alajmi A, Yuan Y, Solitano V, Rosenfeld DEC, Estevinho MM, Magro F, Nardone OM, Jairath V. 5-Aminosalicylates for non-surgical patients with active or quiescent Crohn's disease: an overview of systematic reviews (umbrella review). J Crohns Colitis 2025; 19:jjaf069. [PMID: 40255145 DOI: 10.1093/ecco-jcc/jjaf069] [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: 02/19/2025] [Indexed: 04/22/2025]
Abstract
BACKGROUND 5-aminosalicylates (5-ASAs) are commonly used in non-surgical patients with Crohn's disease (CD), especially in mild-to-moderate disease, despite current guidelines against their use. Despite this, the evidence regarding their efficacy is mixed, with conflicting findings in systematic reviews (SRs). AIMS We conducted an overview of reviews (umbrella review) to consolidate existing knowledge from published SRs on using 5-ASAs in patients with active or quiescent CD. METHODS We systematically searched for relevant SRs published in English until July 6, 2024, summarizing data on 5-ASAs used in induction, maintenance, or withdrawal trials of CD. We also searched for placebo-controlled RCTs of 5-ASAs published after 2015. RESULTS Eight SRs met our inclusion criteria, with the number of included RCTs of 5-ASAs in CD ranging from 2 to 22. Two were network meta-analyses (NMA); 4 were Cochrane SRs. SRs found no evidence of benefit for oral 5-ASAs over placebo for maintaining medically induced remission. The latest NMA in 2017, including 22 RCTs for induction of remission, suggested that high-dose mesalamine (≥ 2.4 g) was more effective than placebo, though ranking lower than systemic corticosteroid and high-dose budesonide. No placebo-controlled RCT of 5-ASAs was published after 2015, only the ongoing STATIC trial is investigating the withdrawal of 5-ASAs in patients with quiescent CD. CONCLUSION This overview of SRs suggests that the evidence does not support the use of 5-ASAs for maintaining medically induced remission. However, high-dose mesalamine may be considered for inducing remission in selected patients with mild luminal CD who prefer to avoid steroids.
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Affiliation(s)
- Abdulaziz Alajmi
- Department of Medicine, London Health Science Center, London, Ontario, Canada
| | - Yuhong Yuan
- Department of Medicine, London Health Science Center, London, Ontario, Canada
- Department of Medine, Western University, London, Ontario, Canada
| | - Virginia Solitano
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | | | - Maria Manuela Estevinho
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Gastroenterology, Unidade Local de Saúde Gaia Espinho, Vila Nova de Gaia, Portugal
| | - Fernando Magro
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Gastroenterology, Unidade Local de Saúde de São João, Porto, Portugal
| | - Olga Maria Nardone
- Gastroenterology, Department of Public Health, University Federico II of Naples, Naples, Italy
| | - Vipul Jairath
- Department of Medicine, London Health Science Center, London, Ontario, Canada
- Department of Medine, Western University, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
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Silva R, de Azevedo JN, Machado JP, Rodrigues JM. Placebo-Controlled Trials in the Management of Crohn's Disease: An Umbrella Review of Meta-Analyses. Med Sci (Basel) 2025; 13:12. [PMID: 39982236 PMCID: PMC11843887 DOI: 10.3390/medsci13010012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/22/2025] [Accepted: 01/27/2025] [Indexed: 02/22/2025] Open
Abstract
INTRODUCTION Crohn's disease is a chronic inflammatory bowel disease characterized by abdominal pain, diarrhea, and other symptoms. It can lead to significant complications and impact patients' quality of life. Therefore, effective management strategies are essential for improving outcomes. METHODS To assess the efficacy of the treatments for Crohn's disease, this umbrella review systematically addresses systematic reviews and meta-analyses on Crohn's disease management published between 2013 and 2023. The quality of the included studies was assessed using the National Institutes of Health's quality assessment tool. RESULTS Sixteen studies were included, evaluating various interventions for the induction and maintenance of remission. These included biologic agents (anti-TNF agents, anti-IL-12/23p40 antibodies, and integrin receptor antagonists), antimetabolites, and corticosteroids. CONCLUSIONS The findings suggest that biologic agents may be promising options for both the induction and maintenance of remission in Crohn's disease. Antimetabolites and corticosteroids may be effective in certain cases, but their efficacy and safety profiles require further investigation. The included studies varied in quality and sample size. More research is needed to confirm the findings and establish optimal treatment strategies. Moreover, while biologic agents show promise, the optimal management of Crohn's disease requires further research. A personalized approach considering patient factors and disease characteristics is crucial for optimizing outcomes.
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Affiliation(s)
- Richard Silva
- Clínica Médica Dr. Richard, 3700-317 São João da Madeira, Portugal
| | | | - Jorge Pereira Machado
- ICBAS, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
- CBSin—Center of BioSciences in Integrative Health, 4000-105 Porto, Portugal
| | - Jorge Magalhães Rodrigues
- ICBAS, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
- CBSin—Center of BioSciences in Integrative Health, 4000-105 Porto, Portugal
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Oizumi T, Toya Y, Yanai S, Matsumoto T. Clinical Features of Thiopurine-Induced Acute Pancreatitis: Comparison Between Patients With and Without Inflammatory Bowel Disease. CROHN'S & COLITIS 360 2025; 7:otae072. [PMID: 39917028 PMCID: PMC11799739 DOI: 10.1093/crocol/otae072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Indexed: 02/09/2025] Open
Abstract
Background and Aims Patients with inflammatory bowel disease (IBD) are at increased risk of developing acute pancreatitis (AP). Thiopurines (TP) are a well-known cause of AP. The aims of this study were to compare the incidence of AP and TP-induced AP (TIP) between patients with and without IBD under the use of TP and to assess for risk factors of TIP. Methods We examined a retrospective cohort of 664 patients treated with TP from 2016 to 2021 at our institution. AP was defined as pancreatitis confirmed by symptoms, serum tests, and radiology, and TIP as AP occurring shortly after starting TP and improving after withdrawal. We compared the incidence of AP and TIP between patients with and without IBD and reviewed the clinical features of TIP patients in detail. Results There were 366 IBD patients and 298 without IBD. IBD patients included 249 males (52.4%) with a median age of 39 years. Among them, 211 had ulcerative colitis (UC) and 155 had Crohn's disease (CD). Azathioprine was administered to 560 patients, and 6-mercaptopurine to 104. AP occurred in 13 IBD patients but in none without IBD, with a significantly higher incidence in IBD patients (1.9% vs. 0%, P = .009). Seven of 13 patients with AP satisfied the criteria for TIP. Furthermore, 5 of the 7 TIP patients had a prior history of 5-aminosalicylic acid (5-ASA) intolerance. Conclusions TIP may be a condition specific to IBD. IBD patients with 5-ASA intolerance are prone to TIP.
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Affiliation(s)
- Tomofumi Oizumi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Yahaba, Iwate, Japan
| | - Yosuke Toya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Yahaba, Iwate, Japan
| | - Shunichi Yanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Yahaba, Iwate, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Yahaba, Iwate, Japan
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Rogler G. [Efficient treatment of mild Crohn's disease and mild ulcerative colitis]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2025; 66:15-21. [PMID: 39715834 PMCID: PMC11761793 DOI: 10.1007/s00108-024-01840-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/12/2024] [Indexed: 12/25/2024]
Abstract
The cornerstone of treatment for mild ulcerative colitis is still the oral or topical (rectal) application of aminosalicylates (5-ASA). 5‑ASA preparations are often only administered orally in mild ulcerative colitis. Study data show that in ulcerative proctitis and left-sided colitis, rectal 5‑ASA preparations are even more effective than oral administration. In a next step, steroid-containing topical therapies should be used. Topical steroids such as budesonide are also primarily used in mild Crohn's disease. However, it is controversial whether treatment is necessary in symptom-free patients. There is still a lack of evidence to prove that more aggressive treatment (using immunosuppressants, biologics or small molecules) has a long-term benefit in these patients. Most guidelines are critical of the use of 5‑ASA in mild Crohn's disease. Nevertheless, there is some evidence for sufficiently high-dose treatment with 5‑ASA, although one must be aware of its limited effectiveness. However, there is clear evidence for the postoperative use of 5‑ASA in cases of mild recurrence.
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Affiliation(s)
- Gerhard Rogler
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Rämistrasse 100, 8091, Zürich, Schweiz.
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Gordon H, Minozzi S, Kopylov U, Verstockt B, Chaparro M, Buskens C, Warusavitarne J, Agrawal M, Allocca M, Atreya R, Battat R, Bettenworth D, Bislenghi G, Brown SR, Burisch J, Casanova MJ, Czuber-Dochan W, de Groof J, El-Hussuna A, Ellul P, Fidalgo C, Fiorino G, Gisbert JP, Sabino JG, Hanzel J, Holubar S, Iacucci M, Iqbal N, Kapizioni C, Karmiris K, Kobayashi T, Kotze PG, Luglio G, Maaser C, Moran G, Noor N, Papamichael K, Peros G, Reenaers C, Sica G, Sigall-Boneh R, Vavricka SR, Yanai H, Myrelid P, Adamina M, Raine T. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis 2024; 18:1531-1555. [PMID: 38877997 DOI: 10.1093/ecco-jcc/jjae091] [Citation(s) in RCA: 56] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Indexed: 07/28/2024]
Affiliation(s)
- Hannah Gordon
- Translational Gastroenterology and Liver Unit, University of Oxford, Oxford, UK
| | - Silvia Minozzi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Bram Verstockt
- Department Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - María Chaparro
- Gastroenterology Department. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Christianne Buskens
- Department of Surgery, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands
| | | | - Manasi Agrawal
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Mariangela Allocca
- IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy
| | - Raja Atreya
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Robert Battat
- Division of Gastroenterology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Dominik Bettenworth
- CED Schwerpunktpraxis, Münster and Medical Faculty of the University of Münster, Münster, Germany
| | - Gabriele Bislenghi
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | | | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults; Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - María José Casanova
- Gastroenterology Department. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Wladyslawa Czuber-Dochan
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK
| | - Joline de Groof
- Colorectal Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Alaa El-Hussuna
- Department of Surgery, OpenSourceResearch Organization [OSRC.Network], Aalborg, Denmark
| | - Pierre Ellul
- Division of Gastroenterology, Mater Dei Hospital, L-Imsida, Malta
| | - Catarina Fidalgo
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
- Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
| | | | - Javier P Gisbert
- Gastroenterology Department. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - João Guedelha Sabino
- Department Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Jurij Hanzel
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Stefan Holubar
- Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Nusrat Iqbal
- Department of Surgery, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
| | | | | | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná [PUCPR], Curitiba, Brazil
| | - Gaetano Luglio
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Christian Maaser
- Outpatients Department of Gastroenterology, University Teaching Hospital Lueneburg, Lueneberg, Germany
| | - Gordon Moran
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
- Translational Medical Sciences, School of Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Nurulamin Noor
- Department of Medicine, University of Cambridge, School of Clinical Medicine, Cambridge, UK
| | - Konstantinos Papamichael
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Georgios Peros
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
| | | | - Giuseppe Sica
- Department of Surgery, Università Tor Vergata, Roma, Italy
| | - Rotem Sigall-Boneh
- Pediatric Gastroenterology and Nutrition Unit, E. Wolfson Medical Center, Holon, Israel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva; Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Pär Myrelid
- Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Michel Adamina
- Department of Surgery, Cantonal Hospital of Fribourg & Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Gisbert JP, Chaparro M. Common Mistakes in Managing Patients with Inflammatory Bowel Disease. J Clin Med 2024; 13:4795. [PMID: 39200937 PMCID: PMC11355176 DOI: 10.3390/jcm13164795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
Introduction: Errors are very common in medical practice and in particular, in the healthcare of patients with inflammatory bowel disease (IBD); however, most of these can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to this problem consists in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation for each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, elderly patients, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for a greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it is desirable to follow IBD patients in specialized units, which would undoubtedly be associated with higher-quality healthcare and a lower likelihood of errors in managing these patients.
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Affiliation(s)
- Javier P. Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain;
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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Wang K, Wang M, Li W, Wang X. A real-world disproportionality analysis of Tivozanib data mining of the public version of FDA adverse event reporting system. Front Pharmacol 2024; 15:1408135. [PMID: 38939844 PMCID: PMC11208458 DOI: 10.3389/fphar.2024.1408135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 05/21/2024] [Indexed: 06/29/2024] Open
Abstract
Background Tivozanib, a vascular endothelial growth factor tyrosine kinase inhibitor, has demonstrated efficacy in a phase III clinical trials for the treatment of renal cell carcinoma. However, comprehensive evaluation of its long-term safety profile in a large sample population remains elusive. The current study assessed Tivozanib-related adverse events of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System. Methods Disproportionality analyses, utilizing reporting odds ratio proportional reporting ratio Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker (MGPS) algorithms, were conducted to quantify signals of Tivozanib-related AEs. Weibull distribution was used to predict the varying risk incidence of AEs over time. Results Out of 5,361,420 reports collected from the FAERS database, 1,366 reports of Tivozanib-associated AEs were identified. A total of 94 significant disproportionality preferred terms (PTs) conforming to the four algorithms simultaneously were retained. The most common AEs included fatigue, diarrhea, nausea, blood pressure increased, decreased appetite, and dysphonia, consistent with prior specifications and clinical trials. Unexpected significant AEs such as dyspnea, constipation, pain in extremity, stomatitis, and palmar-plantar erythrodysaesthesia syndrome was observed. The median onset time of Tivozanib-related AEs was 37 days (interquartile range [IQR] 11.75-91 days), with a majority (n = 127, 46.35%) occurring within the initial month following Tivozanib initiation. Conclusion Our observations align with clinical assertions regarding Tivozanib's safety profile. Additionally, we unveil potential novel and unexpected AE signatures associated with Tivozanib administration, highlighting the imperative for prospective clinical studies to validate these findings and elucidate their causal relationships. These results furnish valuable evidence to steer future clinical inquiries aimed at elucidating the safety profile of Tivozanib.
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Affiliation(s)
- Kaixuan Wang
- Department of Urology Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Mengmeng Wang
- Department of Oncology, the Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | - Wensheng Li
- Department of Urology Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Xiaohui Wang
- Department of Urology Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
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Liu M, Gu L, Zhang Y, Zhou H, Wang Y, Xu ZX. A real-world disproportionality analysis of mesalazine data mining of the public version of FDA adverse event reporting system. Front Pharmacol 2024; 15:1290975. [PMID: 38357304 PMCID: PMC10864552 DOI: 10.3389/fphar.2024.1290975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 01/18/2024] [Indexed: 02/16/2024] Open
Abstract
Background: Mesalazine, a preparation of 5-aminosalicylic acid, is a medication widely used in clinical practice as a first-line therapy in the treatment of mild and moderate inflammatory bowel disease. However, the long-term safety of mesalazine in large sample population was unknown. The current study was to assess mesalazine -related adverse events of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio the Bayesian confidence propagation neural network and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of mesalazine -associated AEs. Results: Out of 14,149,980 reports collected from the FDA Adverse Event Reporting System database, 24,284 reports of mesalazine -associated AEs were identified. A total of 170 significant disproportionality preferred terms conforming to the four algorithms simultaneously were retained. The most common AEs included colitis ulcerative, diarrhoea, condition aggravated, crohn's disease, fatigue, abdominal pain, nausea, haematochezia, which were corresponding to those reported in the specification and clinical trials. Unexpected significant AEs as dizziness, drug ineffective, drug hypersensitivity, infection, off label use, weight decreased, decreased appetite, arthralgia, rash might also occur. The median onset time of mesalazine -related AEs was 1,127 days (interquartile range [IQR] 1,127-1,674 days), and most of the cases occurred 2 years later (n = 610, 70.93%) and within the first 1 month (n = 89, 10.35%) after mesalazine initiation. Conclusion: Results of our study were consistent with clinical observations. We also found potential new and unexpected AEs signals for mesalazine, suggesting prospective clinical studies were needed to confirm these results and illustrate their relationship. Our results could provide valuable evidence for further safety studies of mesalazine.
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Affiliation(s)
- Mingdi Liu
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
| | - Liting Gu
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
| | - Yuning Zhang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
| | - Honglan Zhou
- Department of Urology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yishu Wang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
| | - Zhi-Xiang Xu
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
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10
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Herrlinger KR, Stange EF. Prioritization in inflammatory bowel disease therapy. Expert Rev Gastroenterol Hepatol 2023; 17:753-767. [PMID: 37480322 DOI: 10.1080/17474124.2023.2240699] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 06/24/2023] [Accepted: 07/21/2023] [Indexed: 07/24/2023]
Abstract
INTRODUCTION Most guidelines for IBD still recommend step-by-step therapy with initially classic drugs such aminosalicylates (in ulcerative colitis) or steroids but avoid prioritizing certain biological drugs and JAK inhibitors in the complicated course. This review provides an aid to pending therapy decisions. AREAS COVERED In this review, we analyze the evidence for Crohn's disease as well as ulcerative colitis in order to optimize and 'personalize' the choice of therapy, especially in difficult cases. The relevant publications in Pubmed were identified in a continuous literature review with the key words 'Crohn´s disease' and 'ulcerative colitis.' EXPERT OPINION Based on this complex data set following standard therapies steroid-refractory Crohn´s disease should preferentially be treated with combined infliximab plus azathioprine or risankizumab, in second line after their failure with ustekinumab or 7adalimumab. In steroid-refractory ulcerative colitis infliximab plus azathioprine or upadacitinib should be preferred in first line, filgotinib, tofacitinib or ustekinumab in second line. A steroid-dependent course in both diseases requires azathioprine or vedolizumab, in second line infliximab or Janus kinase inhibitors. The conclusions drawn from these complex data may be helpful for individual decision making in daily clinical practice.
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Affiliation(s)
| | - Eduard F Stange
- Klinik Für Innere Medizin I, Universitätsklinik Tübingen, Tübingen, Germany
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11
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Castillo-Regalado E, Ríos R, Aràjol C, Gely C, Márquez L, Calafat M, González-Muñoza C, Cañete F, Mesonero F, Guardiola J, Garcia-Planella E, Mañosa M, Domènech E. Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:164-170. [PMID: 36179946 DOI: 10.1016/j.gastrohep.2022.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/05/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. METHODS Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. RESULTS Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48-234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5-187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. CONCLUSIONS 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.
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Affiliation(s)
- Edgar Castillo-Regalado
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
| | - Raquel Ríos
- Department of Gastroenterology, Hospital Ramón y Cajal, Madrid, Spain
| | - Clàudia Aràjol
- Department of Gastroenterology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain
| | - Cristina Gely
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain
| | - Lucía Márquez
- Department of Gastroenterology, Hospital del Mar, Barcelona, Catalonia, Spain
| | - Margalida Calafat
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Carlos González-Muñoza
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain
| | - Fiorella Cañete
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Jordi Guardiola
- Department of Gastroenterology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain
| | - Esther Garcia-Planella
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain
| | - Míriam Mañosa
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Eugeni Domènech
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
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12
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Mosli MH, Almudaiheem HY, AlAmeel T, Bakkari SA, Alharbi OR, Alenzi KA, Khardaly AM, AlMolaiki MA, Al-Omari BA, Albarakati RG, Al-Jedai AH, Saadah OI, Almadi MA, Al-Bawardy B. Saudi Arabia consensus guidance for the diagnosis and management of adults with inflammatory bowel disease. Saudi J Gastroenterol 2022; 29:361671. [PMID: 36412460 PMCID: PMC10540981 DOI: 10.4103/sjg.sjg_277_22] [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: 06/24/2022] [Revised: 08/23/2022] [Accepted: 09/05/2022] [Indexed: 02/10/2023] Open
Abstract
Optimal management of inflammatory bowel disease (IBD) relies on a clear understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This article provides concise guidelines for the management of IBD in adults, based on the most up-to-date information at the time of writing and will be regularly updated. These guidelines were developed by the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacy. After an extensive literature review, 78 evidence-and expert opinion-based recommendations for diagnosing and treating ulcerative colitis and Crohn's disease in adults were proposed and further refined by a voting process. The consensus guidelines include the finally agreed on statements with their level of evidence covering different aspects of IBD diagnosis and treatment.
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Affiliation(s)
- Mahmoud H. Mosli
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | | | - Turki AlAmeel
- Department of Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Shakir A. Bakkari
- Division of Gastroenterology, King Saud Medical City, Riyadh, Saudi Arabia
| | - Othman R. Alharbi
- Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Khalidah A. Alenzi
- Regional Drug Information and Pharmacovigilance Center, Ministry of Health, Tabuk, Saudi Arabia
| | | | - Maha A. AlMolaiki
- Department of Pharmaceutical Care, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Bedor A. Al-Omari
- Pharmaceutical Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Rayan G. Albarakati
- Department of Obstetrics and Gynecology, Majmaah University, Riyadh, Saudi Arabia
| | - Ahmed H. Al-Jedai
- Deputyship of Therapeutic Affairs, Ministry of Health, Riyadh, Saudi Arabia
| | - Omar I. Saadah
- Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Majid A. Almadi
- Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Badr Al-Bawardy
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
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13
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Kjeldsen S, Nielsen J, Mertz Nørgård B, Kjeldsen J. Mesalazine in Inflammatory Bowel Disease and COVID-19: Hospitalization and Adverse In-Hospital Outcomes Based on Nationwide Data. Inflamm Bowel Dis 2022; 28:1513-1519. [PMID: 34849917 PMCID: PMC8822411 DOI: 10.1093/ibd/izab299] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND We assessed whether 5-aminosalicylic acid (5-ASA), as treatment for inflammatory bowel disease (IBD), was associated with an increase in hospitalization for coronavirus disease 2019 and adverse in-hospital outcomes. METHODS This was a Danish nationwide register study. The study population consisted of all patients with an IBD diagnosis between March 1, 2010, and March 1, 2020, and living in Denmark on March 1, 2020. Patients with IBD treated with 5-ASA (exposed) were compared with patients not receiving 5-ASA (unexposed). RESULTS We identified 60 242 patients with IBD; 15 635 (40.5%) with ulcerative colitis (UC) and 964 (4.5%) with Crohn's disease (CD) were exposed to 5-ASA. For patients with UC who were 5-ASA exposed, the hazard ratio of hospitalization was 1.18 (95% confidence interval, 0.79-1.78). In-hospital outcomes were not statistical significant from those not exposed to 5-ASA (median length of hospital stay 5.6 days vs 7.2 days), mechanical ventilation (0% vs 14%), continuous positive airway pressure (7.9% vs 9.4%), and in-hospital mortality (21.1% vs 17.2%). For patients with CD, the hazard ratio of hospitalization was 2.25 (95% confidence interval, 1.02-4.97). We found no statistically significant difference in length of hospital stay (7.1 days vs 3.9 days), mechanical ventilation (0% vs 1.8%), use of continuous positive airway pressure (0% vs 1.8%), or in-hospital mortality (0% vs 9%) between exposed and unexposed patients. CONCLUSIONS Patients with UC, treated with 5-ASA, had no increased risk of hospitalization for coronavirus disease 2019 or more adverse in-hospital outcomes. In patients with CD, 5-ASA may be associated with an increased risk of hospitalization but not with more adverse in-hospital outcomes.
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Affiliation(s)
- Simon Kjeldsen
- Department of Acute Medicine, Regional Hospital Central Jutland, Viborg, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jan Nielsen
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jens Kjeldsen
- Department of Medical Gastroenterology S, Odense University Hospital, Odense, Denmarkand
- Research Unit of Medical Gastroenterology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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14
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignaß A, Ehehalt R, Germer C, Grunert PC, Helwig U, Herrlinger K, Kienle P, Kreis ME, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – August 2021 – AWMF-Registernummer: 021-004. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:332-418. [PMID: 35263784 DOI: 10.1055/a-1713-3941] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Axel Dignaß
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Christoph Germer
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Deutschland
| | - Philip C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Martin E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | | | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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15
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Kumar A, Cole A, Segal J, Smith P, Limdi JK. A review of the therapeutic management of Crohn's disease. Therap Adv Gastroenterol 2022; 15:17562848221078456. [PMID: 35198041 PMCID: PMC8859667 DOI: 10.1177/17562848221078456] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 01/19/2022] [Indexed: 02/04/2023] Open
Abstract
Crohn's disease is a chronic inflammatory, relapsing-remitting, and progressive gastrointestinal disorder with an often-negative impact on the physical, emotional, and psychological well-being. Over the past two decades, the medical compendium for the treatment of Crohn's disease has increased significantly, enabling treatment beyond symptoms. Indeed, early and timely use of effective medical therapy has been reflected by improved outcomes with reduction in surgery and ability to achieve clinical and endoscopic remission, reduce corticosteroid dependance, and prevent long-term complications in more patients. In this review, we discuss the key milestones in the medical management of Crohn's disease.
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Affiliation(s)
- Aditi Kumar
- Gastroenterology Department, The Royal Wolverhampton NHS Trust, Wolverhampton WV10 0QP, UK
| | | | - Jonathan Segal
- Department of Gastroenterology and Hepatology, St Mary’s Hospital, London, UK
| | - Philip Smith
- Department of Gastroenterology, The Royal Liverpool and Broadgreen University Hospitals, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Faculty of Medicine, University of Liverpool, Liverpool, UK
| | - Jimmy K. Limdi
- Department of Gastroenterology, Northern Care Alliance NHS Foundation NHS Trust, Manchester, UK
- Manchester Academic Health Sciences, University of Manchester, Manchester, UK
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16
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Qv L, Mao S, Li Y, Zhang J, Li L. Roles of Gut Bacteriophages in the Pathogenesis and Treatment of Inflammatory Bowel Disease. Front Cell Infect Microbiol 2021; 11:755650. [PMID: 34900751 PMCID: PMC8656360 DOI: 10.3389/fcimb.2021.755650] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are chronic, relapsing intestinal inflammatory disorders. Although the molecular mechanisms governing the pathogenesis of IBD are not completely clear, the main factors are presumed to be a complex interaction between genetic predisposition, host immune response and environmental exposure, especially the intestinal microbiome. Currently, most studies have focused on the role of gut bacteria in the onset and development of IBD, whereas little attention has been paid to the enteroviruses. Among of them, viruses that infect prokaryotes, called bacteriophages (phages) occupy the majority (90%) in population. Moreover, several recent studies have reported the capability of regulating the bacterial population in the gut, and the direct and indirect influence on host immune response. The present review highlights the roles of gut phages in IBD pathogenesis and explores the potentiality of phages as a therapeutic target for IBD treatment.
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Affiliation(s)
- Lingling Qv
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Sunbing Mao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yongjun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jia Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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17
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Łodyga M, Eder P, Gawron-Kiszka M, Dobrowolska A, Gonciarz M, Hartleb M, Kłopocka M, Małecka-Wojciesko E, Radwan P, Reguła J, Zagórowicz E, Rydzewska G. Guidelines for the management of patients with Crohn's disease. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. PRZEGLAD GASTROENTEROLOGICZNY 2021; 16:257-296. [PMID: 34976235 PMCID: PMC8690943 DOI: 10.5114/pg.2021.110914] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 10/25/2021] [Indexed: 12/13/2022]
Abstract
This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2012. It contains 46 recommendations for the diagnosis and treatment, both pharmacological and surgical, of Crohn's disease in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality and strength of the available recommendations. The degree of expert support for the proposed statement, assessment of the quality of evidence and the strength of the recommendation was assessed on a 6-point Likert scale. Voting results, quality and strength ratings with comments are included with each statement.
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Affiliation(s)
- Michał Łodyga
- Department of Gastroenterology with the Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland
| | - Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Heliodor Święcicki University Hospital, Poznan, Poland
| | - Magdalena Gawron-Kiszka
- Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Heliodor Święcicki University Hospital, Poznan, Poland
| | - Maciej Gonciarz
- Department of Gastroenterology and Internal Medicine, Military Institute of Medicine, Warsaw, Poland
| | - Marek Hartleb
- Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
| | - Maria Kłopocka
- Department of Gastroenterology and Nutritional Disorders, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | | | - Piotr Radwan
- Department of Gastroenterology, Medical University of Lublin, Lublin, Poland
| | - Jarosław Reguła
- Department of Gastroenterology, Hepatology and Clinical Oncology, Center of Postgraduate Medical Education, Warsaw, Poland
- Department of Oncological Gastroenterology, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Edyta Zagórowicz
- Department of Gastroenterology, Hepatology and Clinical Oncology, Center of Postgraduate Medical Education, Warsaw, Poland
- Department of Oncological Gastroenterology, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Grażyna Rydzewska
- Department of Gastroenterology with the Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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18
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Vieira CP, Rosario AILS, Lelis CA, Rekowsky BSS, Carvalho APA, Rosário DKA, Elias TA, Costa MP, Foguel D, Conte-Junior CA. Bioactive Compounds from Kefir and Their Potential Benefits on Health: A Systematic Review and Meta-Analysis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:9081738. [PMID: 34745425 PMCID: PMC8566050 DOI: 10.1155/2021/9081738] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 10/07/2021] [Indexed: 11/21/2022]
Abstract
Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still absent in the literature. Kefir is fermented milk resulting from the metabolism of a complex microbiota in symbiosis. Recent researches have investigated the bioactive compounds responsible for the preventive and therapeutic effects attributed to kefir. However, differences in functional potential between industrial and artisanal kefir are still controversial. Firstly, we identified differences in the microbial composition among both types of kefir. Available evidence concerning the action of different bioactive compounds from kefir on health, both from in vitro and in vivo studies, was subsequently summarized to draw a primary conclusion of the dose and the intervention time for effect, the producer microorganisms, the precursor in the milk, and the action mechanism. Meta-analysis was performed to investigate the statistically significant differences (P < 0.05) between intervention and control and between both types of kefir for each health effect studied. In summary, the bioactive compounds more commonly reported were exopolysaccharides, including kefiran, bioactive peptides, and organic acids, especially lactic acid. Kefir bioactive compounds presented antimicrobial, anticancer, and immune-modulatory activities corroborated by the meta-analysis. However, clinical evidence is urgently needed to strengthen the practical applicability of these bioactive compounds. The mechanisms of their action were diverse, indicating that they can act by different signaling pathways. Still, industrial and artisanal kefir may differ regarding functional potential-OR of 8.56 (95% CI: 2.27-32.21, P ≤ .001)-according to the observed health effect, which can be associated with differences in the microbial composition between both types of kefir.
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Affiliation(s)
- Carla P. Vieira
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-598, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
| | - Anisio Iuri L. S. Rosario
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
- Laboratory of Inspection and Technology of Milk and Derivatives, Escola de Medicina Veterinária e Zootecnia, Universidade Federal da Bahia, 40170-110 Bahia, Brazil
| | - Carini A. Lelis
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-598, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
| | - Bruna Samara S. Rekowsky
- Laboratory of Inspection and Technology of Milk and Derivatives, Escola de Medicina Veterinária e Zootecnia, Universidade Federal da Bahia, 40170-110 Bahia, Brazil
| | - Anna Paula A. Carvalho
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-598, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
| | - Denes Kaic A. Rosário
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-598, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
| | - Thaísa A. Elias
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
| | - Marion P. Costa
- Laboratory of Inspection and Technology of Milk and Derivatives, Escola de Medicina Veterinária e Zootecnia, Universidade Federal da Bahia, 40170-110 Bahia, Brazil
| | - Debora Foguel
- Laboratory of Protein Aggregation and Amyloidosis, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, Brazil
| | - Carlos A. Conte-Junior
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-598, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
- Graduate Program in Sanitary Surveillance (PPGVS), National Institute of Health Quality Control (INCQS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ 21040-900, Brazil
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19
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Alkhatry M, Al-Rifai A, Annese V, Georgopoulos F, Jazzar AN, Khassouan AM, Koutoubi Z, Nathwani R, Taha MS, Limdi JK. First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus. World J Gastroenterol 2020; 26:6710-6769. [PMID: 33268959 PMCID: PMC7684461 DOI: 10.3748/wjg.v26.i43.6710] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 07/15/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis and Crohn's disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.
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Affiliation(s)
- Maryam Alkhatry
- Gastroenterology and Endoscopy Department, Ibrahim Bin Hamad Obaid Allah Hospital, Ministry of Health and Prevention, Ras Al Khaiman, United Arab Emirates
| | - Ahmad Al-Rifai
- Department of Gastroenterology, Sheikh Shakbout Medical City, Abu Dhabi, United Arab Emirates
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic, Dubai, United Arab Emirates
- Department of Gastroenterology and Endoscopy, American Hospital, Dubai, United Arab Emirates
| | | | - Ahmad N Jazzar
- Gastroenterology Division, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Ahmed M Khassouan
- Digestive Disease Unit, Rashid Hospital, Dubai, United Arab Emirates
| | - Zaher Koutoubi
- Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates
| | - Rahul Nathwani
- Department of Gastroenterology, Mediclinic City Hospital, Dubai, United Arab Emirates
- Department of Gastroenterology, Mohammed Bin Rashid University, Dubai, United Arab Emirates
| | - Mazen S Taha
- Gastroenterology and Hepatology, Tawam Hospital, Al Ain, United Arab Emirates
| | - Jimmy K Limdi
- Department of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester Academic Health Sciences, University of Manchester, Manchester M8 5RB, United Kingdom
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20
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Petagna L, Antonelli A, Ganini C, Bellato V, Campanelli M, Divizia A, Efrati C, Franceschilli M, Guida AM, Ingallinella S, Montagnese F, Sensi B, Siragusa L, Sica GS. Pathophysiology of Crohn's disease inflammation and recurrence. Biol Direct 2020; 15:23. [PMID: 33160400 PMCID: PMC7648997 DOI: 10.1186/s13062-020-00280-5] [Citation(s) in RCA: 134] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 02/07/2023] Open
Abstract
Chron's Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions influenced by a complex pathogenesis in which inflammation plays a key role. Crohn's disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a TH1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence.
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Affiliation(s)
- L. Petagna
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - A. Antonelli
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - C. Ganini
- Torvergata Oncoscience Research Centre of Excellence, TOR, Department of Experimental Medicine, University Tor Vergata, Rome, Italy
| | - V. Bellato
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - M. Campanelli
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - A. Divizia
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - C. Efrati
- Ospedale Israelitico, Department of Gastroenterology, Rome, Italy
| | - M. Franceschilli
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - A. M. Guida
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - S. Ingallinella
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - F. Montagnese
- Nuovo Ospedale dei Castelli, Endoscopy Unit, Rome, Italy
| | - B. Sensi
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - L. Siragusa
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - G. S. Sica
- Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
- Torvergata Oncoscience Research Centre of Excellence, TOR, Department of Experimental Medicine, University Tor Vergata, Rome, Italy
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21
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Argollo M, Kotze PG, Lamonaca L, Gilardi D, Furfaro F, Yamamoto T, Danese S. Prevention of Postoperative Recurrence in CD: Tailoring Treatment to Patient Profile. Curr Drug Targets 2020; 20:1327-1338. [PMID: 30894106 DOI: 10.2174/1389450120666190320110809] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/08/2019] [Accepted: 03/08/2019] [Indexed: 12/11/2022]
Abstract
Crohn's disease (CD) is an immune-mediated condition characterized by the transmural inflammation of the gut tissue, associated with progressive bowel damage often leading to surgical intervention. As operative resection of the damaged segment is not curative, a majority of patients undergoing intestinal resections for complicated CD present disease recurrence within 3 years after the intervention. Postoperative recurrence can be defined as endoscopic, clinical, radiological or surgical. Endoscopic recurrence rates within 1 year exceed 60% and the severity, according to the Rutgeerts' score, is associated with worse prognosis and can predict clinical recurrence (in up to 1/3 of the patients). Most importantly, about 50% of patients will undergo a reoperation after 10 years of their first intestinal resection. Therefore, the prevention of postoperative recurrence in CD remains a challenge in clinical practice and should be properly managed. We aim to summarize the most recent data on the definition, risk factors, assessment and treatment of postoperative CD recurrence.
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Affiliation(s)
- Marjorie Argollo
- Department of Gastroenterology, Universidade Federal de São Paulo, São Paulo, Brazil.,IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Paulo Gustavo Kotze
- IBD outpatient clinics, Catholic University of Parana (PUCPR), Curitiba, Brazil
| | - Laura Lamonaca
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Daniela Gilardi
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Federica Furfaro
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Takayuki Yamamoto
- Department of Surgery and IBD Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Japan
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
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22
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Scrivo B, Renna S, Casà A, Monachino N, Macaluso FS, Orlando A. Letter: mesalazine-a safe drug with rare serious adverse events. Aliment Pharmacol Ther 2020; 51:1210-1211. [PMID: 32424923 DOI: 10.1111/apt.15691] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
| | - Sara Renna
- IBD Unit, Villa Sofia Cervello Hospital, Palermo, Italy
| | - Angelo Casà
- IBD Unit, Villa Sofia Cervello Hospital, Palermo, Italy
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23
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Abstract
Mucosal healing (MH) is the goal of the “treat to target” strategy in Crohn's disease (CD), which seeks to prevent disability. However, evidence is limited regarding whether achieving MH can reduce disability in CD. We aimed to estimate the probability of disabling disease and to investigate the association between MH and disabling disease in CD.
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24
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Nguyen NH, Singh S, Sandborn WJ. Positioning Therapies in the Management of Crohn's Disease. Clin Gastroenterol Hepatol 2020; 18:1268-1279. [PMID: 31676360 PMCID: PMC7183879 DOI: 10.1016/j.cgh.2019.10.035] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/11/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
In the past decade, several new therapies with different mechanisms of action have been approved for the management of moderate to severe Crohn's disease. However, there is limited guidance on optimal positioning of agents as first- or second-line therapies because of the absence of head-to-head trials. Furthermore, given the lack of comparative studies, treatment guidelines have provided limited insight. In this review, we discuss data on key treatment attributes, comparative efficacy and safety, factors predictive of response to each agent, and propose an algorithm for positioning therapies for the management of patients with low-risk and high-risk Crohn's disease.
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Affiliation(s)
- Nghia H. Nguyen
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California,Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California
| | - William J. Sandborn
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California
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25
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Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, Adamina M, Armuzzi A, Bachmann O, Bager P, Biancone L, Bokemeyer B, Bossuyt P, Burisch J, Collins P, El-Hussuna A, Ellul P, Frei-Lanter C, Furfaro F, Gingert C, Gionchetti P, Gomollon F, González-Lorenzo M, Gordon H, Hlavaty T, Juillerat P, Katsanos K, Kopylov U, Krustins E, Lytras T, Maaser C, Magro F, Marshall JK, Myrelid P, Pellino G, Rosa I, Sabino J, Savarino E, Spinelli A, Stassen L, Uzzan M, Vavricka S, Verstockt B, Warusavitarne J, Zmora O, Fiorino G. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis 2020; 14:4-22. [PMID: 31711158 DOI: 10.1093/ecco-jcc/jjz180] [Citation(s) in RCA: 862] [Impact Index Per Article: 172.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Joana Torres
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Glen Doherty
- Centre for Colorectal Disease, St Vincent's University Hospital and University College Dublin, Dublin, Ireland
| | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-IP], Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Michel Adamina
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
- University of Basel, Basel, Switzerland
| | - Alessandro Armuzzi
- IBD Unit, Presidio Columbus Fondazione Policlinico Gemelli Universita Cattolica, Rome, Italy
| | - Oliver Bachmann
- Department of Internal Medicine I, Siloah St. Trudpert Hospital, Pforzheim, Germany
| | - Palle Bager
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Livia Biancone
- Department of Systems Medicine, University 'Tor Vergata' of Rome, Rome, Italy
| | | | - Peter Bossuyt
- Imelda GI Clinical Research Centre, Imelda General Hospital, Bonheiden, Belgium
| | - Johan Burisch
- Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Paul Collins
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Alaa El-Hussuna
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | | | - Federica Furfaro
- IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Christian Gingert
- Visceral Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
- Department of Human Medicine, University of Witten/Herdecke, Witten, Germany
| | | | - Fernando Gomollon
- IBD UNIT, Hospital Clíico Universitario 'Lozano Blesa'; IIS Aragón, CIBEREHD, Zaragoza, Spain
| | - Marien González-Lorenzo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - Tibor Hlavaty
- Fifth Department of Internal Medicine, Comenius University Medical School, Bratislava, Slovakia
| | - Pascal Juillerat
- Division of Gastroenterology & Hepatology, Inselspital Bern, Bern, Switzerland
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Tel-HaShomer Sheba Medical Center, Ramat Gan, Israel; and Sackler Medical School, Tel Aviv, Israel
| | - Eduards Krustins
- Department of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Department of Internal medicine, Riga Stradiņš university, Riga, Latvia
| | | | - Christian Maaser
- Outpatients Department of Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Fernando Magro
- Department of Pharmacology and Therapeutics; Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal
| | - John Kenneth Marshall
- Department of Medicine [Division of Gastroenterology] and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Pär Myrelid
- Department of Surgery, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Universitá degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Isadora Rosa
- Department of Gastroenterology, IPOLFG, Lisbon, Portugal
| | - Joao Sabino
- Department of Gastroenterology and Hepatology, University Hospitals, KU Leuven, Leuven, Belgium
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Antonino Spinelli
- Humanitas Clinical and Research Center, Division of Colon and Rectal Surgery, Humanitas University, Milan, Italy
| | - Laurents Stassen
- Department of General Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Mathieu Uzzan
- Department of Gastroenterology, IBD unit, Beaujon Hospital, APHP, Clichy, France
| | - Stephan Vavricka
- Division of Gastroenterology and Hepatology, University Hospital, Zürich, Switzerland
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
- Department of Chronic Diseases, Metabolism and Ageing, TARGID-IBD, KU Leuven, Leuven, Belgium
| | - Janindra Warusavitarne
- Imperial College London, Department of Surgery and Cancer, St Mark's Hospital, Department of Gastroenterology, London, UK
| | - Oded Zmora
- Department of Surgery, Shamir Medical Center [Assaf Harofe], Tel Aviv, Israel
| | - Gionata Fiorino
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IBD Center, Humanitas Clinical and Research Center, Milan, Italy
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26
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1497] [Impact Index Per Article: 249.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
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27
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Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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28
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Hirakawa H, Tashiro H, Takahashi K, Tanaka M, Sadamatsu H, Kimura S, Sueoka-Aragane N. Mesalazine-induced airway obstruction: Utility of pulmonary function testing in drug-induced lung diseases. Respir Investig 2019; 57:611-614. [PMID: 31601486 DOI: 10.1016/j.resinv.2019.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/20/2019] [Accepted: 09/12/2019] [Indexed: 06/10/2023]
Abstract
Mesalazine is a standard therapeutic agent for the treatment of inflammatory bowel diseases. A rare case of mesalazine-induced airway obstruction documented by pulmonary function testing is reported herein. The patient had Crohn's disease and was treated with mesalazine; she subsequently developed a high fever, cough, and chest pain with centrilobular nodular shadows on chest computed tomography (CT). After cessation of mesalazine, the abnormal CT findings as well as the decreased forced expiratory volume in 1 second improved. Based on these findings, pulmonary function testing appears to be a useful tool, even in the acute phase, along with chest CT in drug-induced lung diseases.
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Affiliation(s)
- Haruki Hirakawa
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga Prefecture, 849-8501, Japan
| | - Hiroki Tashiro
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga Prefecture, 849-8501, Japan.
| | - Koichiro Takahashi
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga Prefecture, 849-8501, Japan
| | - Masahide Tanaka
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga Prefecture, 849-8501, Japan
| | - Hironori Sadamatsu
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga Prefecture, 849-8501, Japan
| | - Shinya Kimura
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga Prefecture, 849-8501, Japan
| | - Naoko Sueoka-Aragane
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga Prefecture, 849-8501, Japan
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Menon S, Bressler B. Editorial: aminosalicylates and nephrotoxicity-an issue put to rest. Aliment Pharmacol Ther 2019; 50:1059. [PMID: 31625190 DOI: 10.1111/apt.15474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Xu Y, Guo Z, Huang L, Gong J, Li Y, Gu L, Shen W, Zhu W. A nomogram for predicting the response to exclusive enteral nutrition in adult patients with isolated colonic Crohn's disease. Therap Adv Gastroenterol 2019; 12:1756284819881301. [PMID: 31656533 PMCID: PMC6791043 DOI: 10.1177/1756284819881301] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 09/18/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Isolated colonic Crohn's disease (cCD) responds less well to induction therapy with exclusive enteral nutrition (EEN) compared with ileal or ileocolonic disease in adult patients; therefore, we aimed to identify the factors that influence the response to EEN and develop a predictive nomogram model to optimize the use of EEN in cCD patients. MATERIALS AND METHODS Eighty-five cCD patients treated with EEN as first-line therapy at our center between 1 June 2012 and 30 June 2018 were retrospectively analyzed as the primary cohort. The primary endpoint was clinical remission after EEN therapy. Potential predictive factors for the efficacy of EEN were assessed by univariate and multivariate analyses, and a nomogram to predict the response to EEN therapy in cCD patients was designed. Another 19 cCD patients were retrospectively included in the validation cohort to verify the accuracy of the nomogram model. RESULTS The clinical remission rates for the primary cohort and validation cohort were 52.9% and 47.4%, respectively. Pancolitis was the greatest contributor to the risk of failure to respond to EEN [odds ratio (OR) = 4.896; 95% confidence interval (CI) = 1.223-19.607; p = 0.025], lean body mass index (LBMI), colonic lesion features, simple endoscopic scores for Crohn's disease, C-reactive protein before treatment and ∆prealbumin were also related to the efficacy of EEN in cCD. The nomogram model showed robust discrimination, with an area under the receiving operating characteristic curve of 0.906. CONCLUSION Several predictive factors for response to EEN therapy in cCD adult patients were identified, and a promising nomogram that can predict the effect of EEN in cCD was developed.
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Affiliation(s)
- Yihan Xu
- Nanjing Medical University, Nanjing, China Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Zhen Guo
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Liangyu Huang
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Jianfeng Gong
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Yi Li
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Lili Gu
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Weisong Shen
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Weiming Zhu
- Research Institute of General Surgery, Nanjing Jinling Hospital, 305 Zhongshan East Road, Nanjing 210002, China
- Nanjing Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu 210029, China
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Mack DR, Benchimol EI, Critch J, deBruyn J, Tse F, Moayyedi P, Church P, Deslandres C, El-Matary W, Huynh H, Jantchou P, Lawrence S, Otley A, Sherlock M, Walters T, Kappelman MD, Sadowski D, Marshall JK, Griffiths A. Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn's Disease. J Can Assoc Gastroenterol 2019; 2:e35-e63. [PMID: 31294379 PMCID: PMC6619414 DOI: 10.1093/jcag/gwz018] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND & AIMS We aim to provide guidance for medical treatment of luminal Crohn's disease in children. METHODS We performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn's disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them. RESULTS The consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation. CONCLUSIONS Evidence-based medical treatment of Crohn's disease in children is recommended, with thorough ongoing assessments to define treatment success.
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Affiliation(s)
- David R Mack
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
| | - Eric I Benchimol
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Jeff Critch
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada
| | - Jennifer deBruyn
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Section of Pediatric Gastroenterology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
| | - Frances Tse
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Paul Moayyedi
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Peter Church
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Colette Deslandres
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada
| | - Wael El-Matary
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Section of Pediatric Gastroenterology, Department of Pediatrics, Health Sciences Centre, Winnipeg, Manitoba, Canada
| | - Hien Huynh
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Department of Pediatrics (Gastroenterology), Stollery Children's Hospital, Edmonton, Alberta, Canada
| | - Prévost Jantchou
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada
| | - Sally Lawrence
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Anthony Otley
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Division of Gastroenterology and Nutrition, IWK Health Centre, Halifax, Nova Scotia, Canada
| | - Mary Sherlock
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Division of Pediatric Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - Thomas Walters
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Michael D Kappelman
- Division of Pediatric Gastroenterology, University of North Carolina, Hospital-Children's Specialty Clinic, Chapel Hill, North Carolina
| | - Dan Sadowski
- Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Alberta, Canada
| | - John K Marshall
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Anne Griffiths
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
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Mack DR, Benchimol EI, Critch J, deBruyn J, Tse F, Moayyedi P, Church P, Deslandres C, El-Matary W, Huynh H, Jantchou P, Lawrence S, Otley A, Sherlock M, Walters T, Kappelman MD, Sadowski D, Marshall JK, Griffiths A. Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn's Disease. Gastroenterology 2019; 157:320-348. [PMID: 31320109 DOI: 10.1053/j.gastro.2019.03.022] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 02/28/2019] [Accepted: 03/02/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS We aim to provide guidance for medical treatment of luminal Crohn's disease in children. METHODS We performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn's disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them. RESULTS The consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation. CONCLUSIONS Evidence-based medical treatment of Crohn's disease in children is recommended, with thorough ongoing assessments to define treatment success.
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Affiliation(s)
- David R Mack
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada; Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
| | - Eric I Benchimol
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada; Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Jeff Critch
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada
| | - Jennifer deBruyn
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Section of Pediatric Gastroenterology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
| | - Frances Tse
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Paul Moayyedi
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Peter Church
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Colette Deslandres
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada
| | - Wael El-Matary
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Section of Pediatric Gastroenterology, Department of Pediatrics, Health Sciences Centre, Winnipeg, Manitoba, Canada
| | - Hien Huynh
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Department of Pediatrics (Gastroenterology), Stollery Children's Hospital, Edmonton, Alberta, Canada
| | - Prévost Jantchou
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada
| | - Sally Lawrence
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Anthony Otley
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Division of Gastroenterology and Nutrition, IWK Health Centre, Halifax, Nova Scotia, Canada
| | - Mary Sherlock
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Division of Pediatric Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - Thomas Walters
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Michael D Kappelman
- Division of Pediatric Gastroenterology, University of North Carolina, Hospital-Children's Specialty Clinic, Chapel Hill, North Carolina
| | - Dan Sadowski
- Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Alberta, Canada
| | - John K Marshall
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Anne Griffiths
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada.
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Panaccione R, Steinhart AH, Bressler B, Khanna R, Marshall JK, Targownik L, Afif W, Bitton A, Borgaonkar M, Chauhan U, Halloran B, Jones J, Kennedy E, Leontiadis GI, Loftus EV, Meddings J, Moayyedi P, Murthy S, Plamondon S, Rosenfeld G, Schwartz D, Seow CH, Williams C, Bernstein CN. Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease. Clin Gastroenterol Hepatol 2019; 17:1680-1713. [PMID: 30853616 DOI: 10.1016/j.cgh.2019.02.043] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 02/21/2019] [Accepted: 02/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. METHODS We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. RESULTS The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. CONCLUSIONS Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.
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Affiliation(s)
- Remo Panaccione
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
| | - A Hillary Steinhart
- Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Brian Bressler
- Department of Medicine, Division of Gastroenterology, St Paul's Hospital, Vancouver, British Columbia, Canada
| | - Reena Khanna
- Department of Medicine, University of Western Ontario, London, Ontario, Canada
| | - John K Marshall
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Laura Targownik
- Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Waqqas Afif
- Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Alain Bitton
- Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Mark Borgaonkar
- Faculty of Medicine, Memorial University, St John's, Newfoundland, Canada
| | - Usha Chauhan
- Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Brendan Halloran
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - Jennifer Jones
- Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Erin Kennedy
- Division of General Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Grigorios I Leontiadis
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Jonathan Meddings
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Paul Moayyedi
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Sanjay Murthy
- Division of Gastroenterology, University of Ottawa, Ottawa, Ontario, Canada
| | - Sophie Plamondon
- Department of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada
| | - Greg Rosenfeld
- Division of Gastroenterology, Pacific Gastroenterology Associates, Vancouver, British Columbia, Canada
| | - David Schwartz
- Inflammatory Bowel Disease Center, Vanderbilt University, Nashville, Tennessee
| | - Cynthia H Seow
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | | | - Charles N Bernstein
- Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
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Zhou J, Wu LY, Chen L, Guo YJ, Sun Y, Li T, Zhao JM, Bao CH, Wu HG, Shi Y. Herbs-partitioned moxibustion alleviates aberrant intestinal epithelial cell apoptosis by upregulating A20 expression in a mouse model of Crohn’s disease. World J Gastroenterol 2019; 25:2071-2085. [PMID: 31114134 PMCID: PMC6506586 DOI: 10.3748/wjg.v25.i17.2071] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 03/13/2019] [Accepted: 03/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A20 inhibits intestinal epithelial cell apoptosis in Crohn’s disease, and herbs-partitioned moxibustion (HPM) has been demonstrated to be an effective treatment for Crohn’s disease. However, the mechanism by which HPM reduces intestinal epithelial cell apoptosis in Crohn’s disease has not been thoroughly elucidated to date.
AIM To elucidate whether HPM exerts its effects by upregulating A20 to affect intestinal epithelial cell apoptosis in a Crohn’s disease mouse model.
METHODS In this study, mice with A20 deletion in intestinal epithelial cells (A20IEC-KO) were utilized to establish a Crohn’s disease mouse model with 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration, as well as wild-type mice. Mice were randomly divided into normal control (NC), model control (MC), mesalazine (MESA), and HPM groups. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and serum endotoxin and apoptosis of epithelial cells were evaluated by enzyme-linked immunosorbent assay and terminal dUTP nick-end labeling assay accordingly. The protein expression levels of A20 and tumor necrosis factor receptor 1 (TNFR1)-related signaling molecules were evaluated by Western blot, and co-expression of A20 and TNFR1-associated death domain (TRADD) and co-expression of A20 and receptor-interacting protein 1 (RIP1) were observed by double immunofluorescence staining.
RESULTS The intestinal epithelial barrier was noted to have an improvement in the HPM group of wild-type (WT) mice compared with that in A20IEC-KO mice. Compared with A20 IEC-KO HPM mice, serum endotoxin levels and apoptosis percentages were decreased (P < 0.01), A20 expression levels were increased (P < 0.01), and expression of TNFR1, TRADDD, and RIP1 was decreased in the HPM group of WT mice (PTNFR1 < 0.05, PTRADD < 0.01, PRIP1 < 0.01). Both of the co-expression of A20/TRADD and A20/RIP1 showed a predominantly yellow fluorescence in the HPM group of WT mice, while a predominantly red fluorescence was noted in the HPM group of A20IEC-KO mice.
CONCLUSION Our findings suggest that HPM in treating Crohn’s disease functions possibly via upregulation of the A20 expression level, resulting in downregulation of TNFR1, TRADD, and RIP1 to alleviate increased cell apoptosis in the intestinal epithelial barrier in Crohn's disease.
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Affiliation(s)
- Jing Zhou
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lu-Yi Wu
- Qigong Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
| | - Liu Chen
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ya-Jing Guo
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yi Sun
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Tao Li
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ji-Meng Zhao
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai Institute of Acupuncture-Moxibustion and Meridian, Shanghai 200030, China
| | - Chun-Hui Bao
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai Institute of Acupuncture-Moxibustion and Meridian, Shanghai 200030, China
| | - Huan-Gan Wu
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai Institute of Acupuncture-Moxibustion and Meridian, Shanghai 200030, China
| | - Yin Shi
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Outpatient Department, Shanghai Institute of Acupuncture-Moxibustion and Meridian, Shanghai 200030, China
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Miehlke S, Aust D, Mihaly E, Armerding P, Böhm G, Bonderup O, Fernández-Bañares F, Kupcinskas J, Munck LK, Rehbehn KU, Nacak T, Greinwald R, Münch A. Efficacy and Safety of Budesonide, vs Mesalazine or Placebo, as Induction Therapy for Lymphocytic Colitis. Gastroenterology 2018; 155:1795-1804.e3. [PMID: 30195447 DOI: 10.1053/j.gastro.2018.08.042] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 08/07/2018] [Accepted: 08/23/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Lymphocytic colitis is a common cause of chronic, nonbloody diarrhea. However, the effects of treatment are unclear and randomized placebo-controlled trials were requested in a Cochrane review. We performed a randomized, placebo-controlled, multicenter study to evaluate budesonide and mesalazine as induction therapy for lymphocytic colitis. METHODS Patients with active lymphocytic colitis were randomly assigned to groups given budesonide 9 mg once daily (Budenofalk granules), mesalazine 3 g once daily (Salofalk granules), or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as ≤21 stools (including ≤6 watery stools), in the 7 days before week 8. RESULTS The final analysis included 57 patients (19 per group). Most patients were female (72%) and the mean age was 59 years. The proportion of patients in clinical remission at week 8 was significantly higher in the budesonide group than in the placebo group (intention-to-treat analysis, 79% vs 42%; P = .01). The difference in proportions of patients in clinical remission at week 8 between the mesalazine (63%) and placebo groups was not significant (P = .09). The proportion of patients with histologic remission at week 8 was significantly higher in the budesonide group (68%) vs the mesalazine (26%; P = .02) or placebo (21%; P = .008) groups. The incidence of adverse events was 47.4% in the budesonide group, 68.4% in the mesalazine group, and 42.1% in the placebo group. CONCLUSIONS In a randomized multicenter study, we found oral budesonide 9 mg once daily to be effective and safe for induction of clinical and histologic remission in patients with lymphocytic colitis, compared with placebo. Oral mesalazine 3 g once daily was not significantly better than placebo. ClinicalTrials.gov no: NCT01209208.
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Affiliation(s)
- Stephan Miehlke
- Center for Digestive Diseases, Internal Medicine Center Eppendorf, Hamburg, Germany.
| | - Daniela Aust
- Institute for Pathology, University Hospital Carl Gustav Carus, TU Dresden, Germany
| | - Emese Mihaly
- 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | | | - Günther Böhm
- Internal Medicine and Cardiology, Private Practice, Ludwigshafen am Rhein, Germany
| | - Ole Bonderup
- Diagnostic Center, Section of Gastroenterology, Regional Hospital Silkeborg, Silkeborg, Denmark
| | | | - Juozas Kupcinskas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Lars Kristian Munck
- Zealand University Hospital, Køge, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | | | | | | | - Andreas Münch
- Department of Gastroenterology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
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Sokollik C, Fournier N, Rizzuti D, Braegger CP, Nydegger A, Schibli S, Spalinger J. The Use of 5-Aminosalicylic Acid in Children and Adolescents With Inflammatory Bowel Disease. J Clin Gastroenterol 2018. [PMID: 28644308 DOI: 10.1097/mcg.0000000000000864] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND In ulcerative colitis (UC) 5-aminosalicylic acid (5-ASA) is recommended as primary therapy for mild to moderate disease. Topical 5-ASA has been proven especially effective. In Crohn's disease (CD) the evidence for a beneficial role of 5-ASA is weak. We investigated the use of topical and systemic 5-ASA therapy in children and adolescents with inflammatory bowel disease. MATERIALS AND METHODS Data of patients younger than 18 years, registered between April 2008 and December 2015 in the Swiss Inflammatory Bowel Disease Cohort, were analyzed. RESULTS Three hundred twenty pediatric inflammatory bowel disease patients were included; 189 with CD and 131 with UC. Over one third of UC patients [51 (39%)] received topical 5-ASA therapy and 43 (33%) received combination therapy during their disease course. UC patients with left-sided colitis or proctitis were more likely to receive topical or combination therapy as compared with patients with pancolitis (P<0.001 and <0.001, respectively). An increase in the use of topical 5-ASA therapy in UC patients was noted over time from 5% to 38%. Forty-seven percent of CD patients were treated with oral 5-ASA during their disease course. The usage was stable over time at approximately 15% to 20%. CONCLUSIONS In recent years a very positive trend showing an increase in topical 5-ASA therapy in children and adolescents with UC has been observed. However topical therapy is still used with relative low frequency, especially in patients with a more extensive disease. Conversely, despite weak evidence supporting 5-ASA use in CD patients it has been frequently prescribed. Physicians should continue to encourage their UC patients to use topical therapy.
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Affiliation(s)
- Christiane Sokollik
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital, University of Bern, Bern
| | - Nicolas Fournier
- Institute of Social and Preventive Medicine (IUMSP), University Hospital of Lausanne
| | - David Rizzuti
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital, University of Bern, Bern
| | - Christian P Braegger
- Division of Pediatric Gastroenterology and Nutrition and Children's Research Center, University Children's Hospital of Zurich, Zurich
| | - Andreas Nydegger
- Division of Pediatric Gastroenterology and Hepatology, University Hospital of Lausanne, Lausanne
| | - Susanne Schibli
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital, University of Bern, Bern
| | - Johannes Spalinger
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital, University of Bern, Bern.,Division of Pediatric Gastroenterology, Children's Hospital of Lucerne, Lucerne, Switzerland
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López-Sanromán A, Clofent J, Garcia-Planella E, Menchén L, Nos P, Rodríguez-Lago I, Domènech E. Reviewing the therapeutic role of budesonide in Crohn's disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:458-471. [PMID: 30007787 DOI: 10.1016/j.gastrohep.2018.05.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 05/03/2018] [Indexed: 10/28/2022]
Abstract
Oral budesonide is a glucocorticoid of primarily local action. In the field of digestive diseases, it is used mainly in inflammatory bowel disease, but also in other indications. This review addresses the pharmacology, pharmacodynamics and therapeutic use of budesonide. Its approved indications are reviewed, as well as other clinical scenarios in which it could play a role, in order to facilitate its use and improve the accuracy of its prescription.
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Affiliation(s)
| | - Joan Clofent
- Servicio de Aparato Digestivo, Hospital de Sagunto, Sagunto, Valencia, España
| | | | | | - Pilar Nos
- Hospital Politècnic La Fe, València, España; Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | | | - Eugeni Domènech
- Servei d'Aparell Digestiu, Hospital Germans Trias i Pujol, Badalona, Barcelona, España; Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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Panaccione R, Steinhart AH, Bressler B, Khanna R, Marshall JK, Targownik L, Afif W, Bitton A, Borgaonkar M, Chauhan U, Halloran B, Jones J, Kennedy E, Leontiadis GI, Loftus EV, Meddings J, Moayyedi P, Murthy S, Plamondon S, Rosenfeld G, Schwartz D, Seow CH, Williams C, Bernstein CN. Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease. J Can Assoc Gastroenterol 2018; 2:e1-e34. [PMID: 31294378 PMCID: PMC6619415 DOI: 10.1093/jcag/gwz019] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background & Aims Crohn’s disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. Methods We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. Results The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Conclusions Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.
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Affiliation(s)
- Remo Panaccione
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - A Hillary Steinhart
- Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Brian Bressler
- Department of Medicine, Division of Gastroenterology, St Paul's Hospital, Vancouver, British Columbia, Canada
| | - Reena Khanna
- Department of Medicine, University of Western Ontario, London, Ontario, Canada
| | - John K Marshall
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Laura Targownik
- Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Waqqas Afif
- Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Alain Bitton
- Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Mark Borgaonkar
- Faculty of Medicine, Memorial University, St John's, Newfoundland, Canada
| | - Usha Chauhan
- Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Brendan Halloran
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - Jennifer Jones
- Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Erin Kennedy
- Division of General Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Grigorios I Leontiadis
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Jonathan Meddings
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Paul Moayyedi
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Sanjay Murthy
- Division of Gastroenterology, University of Ottawa, Ottawa, Ontario, Canada
| | - Sophie Plamondon
- Department of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada
| | - Greg Rosenfeld
- Division of Gastroenterology, Pacific Gastroenterology Associates, Vancouver, British Columbia, Canada
| | - David Schwartz
- Inflammatory Bowel Disease Center, Vanderbilt University, Nashville, Tennessee
| | - Cynthia H Seow
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | | | - Charles N Bernstein
- Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
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Ma C, Dutton SJ, Cipriano LE, Singh S, Parker CE, Nguyen TM, Guizzetti L, Gregor JC, Chande N, Hindryckx P, Feagan BG, Jairath V. Systematic review with meta-analysis: prevalence, risk factors and costs of aminosalicylate use in Crohn's disease. Aliment Pharmacol Ther 2018; 48:114-126. [PMID: 29851091 DOI: 10.1111/apt.14821] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 04/13/2018] [Accepted: 05/02/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Aminosalicylates are the most frequently prescribed drugs for patients with Crohn's disease (CD), yet evidence to support their efficacy as induction or maintenance therapy is controversial. AIMS To quantify aminosalicylate use in CD clinical trials, identify factors associated with use and estimate direct annual treatment costs of therapy. METHODS MEDLINE, Embase and CENTRAL were searched to April 2017 for placebo-controlled trials in adults with CD treated with corticosteroids, immunosuppressants or biologics. The proportion of patients co-prescribed aminosalicylates in placebo arms was pooled using a random-effects model. Meta-regression was used to identify factors associated with aminosalicylate use. Annual treatment costs were estimated using the 2016 Ontario Drug Benefit Program. RESULTS Forty-two induction and 10 maintenance trials were included. The pooled proportion of patients co-prescribed aminosalicylates was 44% [95% CI: 39%-49%] in induction trials and 49% [95% CI: 35%-64%] in maintenance trials. There was substantial to considerable heterogeneity (I2 = 86.0%, 91.8% for induction and maintenance trials, respectively). In multivariable meta-regression, aminosalicylate use has decreased over time in induction trials (OR 0.50 [95% CI: 0.34-0.74] per 10-year increment). While a decline has been seen over time, 35% of CD patients were still using aminosalicylates in contemporary trials from the last 5 years. The estimated annual cost for the lowest price mesalazine (mesalamine) formulation is approximately $32 million for the Canadian CD population. CONCLUSIONS Over one-third of CD patients entering clinical trials are still co-prescribed aminosalicylates. A definitive trial is needed to inform the conventional practice of using aminosalicylates as CD maintenance therapy.
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Affiliation(s)
- C Ma
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Robarts Clinical Trials, Western University, London, ON, Canada
| | - S J Dutton
- Oxford Clinical Trials Research Unit and Centre for Statistics in Medicine, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - L E Cipriano
- Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.,Ivey Business School, Western University, London, ON, Canada
| | - S Singh
- Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA.,Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - C E Parker
- Robarts Clinical Trials, Western University, London, ON, Canada
| | - T M Nguyen
- Robarts Clinical Trials, Western University, London, ON, Canada
| | - L Guizzetti
- Robarts Clinical Trials, Western University, London, ON, Canada
| | - J C Gregor
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
| | - N Chande
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
| | - P Hindryckx
- Department of Gastroenterology, University Hospital of Ghent, Ghent, Belgium
| | - B G Feagan
- Robarts Clinical Trials, Western University, London, ON, Canada.,Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.,Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
| | - V Jairath
- Robarts Clinical Trials, Western University, London, ON, Canada.,Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.,Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
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40
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Hatton GB, Madla CM, Rabbie SC, Basit AW. All disease begins in the gut: Influence of gastrointestinal disorders and surgery on oral drug performance. Int J Pharm 2018; 548:408-422. [PMID: 29969711 DOI: 10.1016/j.ijpharm.2018.06.054] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 06/23/2018] [Accepted: 06/25/2018] [Indexed: 02/07/2023]
Abstract
The term "disease" conjures a plethora of graphic imagery for many, and the use of drugs to combat symptoms and treat underlying pathology is at the core of modern medicine. However, the effects of the various gastrointestinal diseases, infections, co-morbidities and the impact of gastrointestinal surgery on the pharmacokinetic and pharmacodynamic behaviour of drugs have been largely overlooked. The better elucidation of disease pathology and the role of underlying cellular and molecular mechanisms have increased our knowledge as far as diagnoses and prognoses are concerned. In addition, the recent advances in our understanding of the intestinal microbiome have linked the composition and function of gut microbiota to disease predisposition and development. This knowledge, however, applies less so in the context of drug absorption and distribution for orally administered dosage forms. Here, we revisit and re-evaluate the influence of a portfolio of gastrointestinal diseases and surgical effects on the functionality of the gastrointestinal tract, their implications for drug delivery and attempt to uncover significant links for clinical practice.
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Affiliation(s)
- Grace B Hatton
- UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London, WC1N 1AX, United Kingdom
| | - Christine M Madla
- UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London, WC1N 1AX, United Kingdom
| | - Sarit C Rabbie
- UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London, WC1N 1AX, United Kingdom
| | - Abdul W Basit
- UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London, WC1N 1AX, United Kingdom.
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41
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Kuenzig ME, Rezaie A, Kaplan GG, Otley AR, Steinhart AH, Griffiths AM, Benchimol EI, Seow CH. Budesonide for the Induction and Maintenance of Remission in Crohn's Disease: Systematic Review and Meta-Analysis for the Cochrane Collaboration. J Can Assoc Gastroenterol 2018; 1:159-173. [PMID: 30656288 PMCID: PMC6328928 DOI: 10.1093/jcag/gwy018] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Budesonide is an oral glucocorticoid designed for the treatment of inflammatory bowel disease (IBD) that may reduce systemic adverse events (AEs). This review examined the efficacy and safety of budesonide for the induction and maintenance of clinical remission in Crohn’s disease (CD). Methods MEDLINE, EMBASE, other electronic databases, reference lists and conference proceedings were searched to November 2017 to identify randomized controlled trials of budesonide. Outcomes were the induction and maintenance of remission at eight weeks and one year, respectively, as well as corticosteroid-related AEs and abnormal adrenocorticotropic hormone (ACTH) tests. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random effects models. Results Thirteen induction and 10 maintenance trials were included. Budesonide 9 mg/day was more effective than placebo (RR 1.93; 95% CI, 1.37–2.73; GRADE: moderate) but less effective than conventional steroids (RR 0.85; 95% CI, 0.75–0.97; GRADE: moderate) to induce remission. Corticosteroid-related AEs occurred less often with induction doses of budesonide than steroids (RR 0.64; 95% CI, 0.54–0.76; GRADE: moderate); budesonide did not increase AEs relative to placebo (RR 0.97; 95% CI, 0.76–1.23; GRADE: moderate). Budesonide 6 mg/day was not different from placebo for maintaining remission (RR 1.13; 95% CI, 0.94–1.35; GRADE: moderate). Both induction (GRADE: low for 3 mg/day, moderate for 9 mg/day) and maintenance budesonide treatment (GRADE: very low for 3 mg/day, low for 6 mg/day) increased the risk of an abnormal ACTH test compared with placebo, but less than conventional steroids (GRADE: very low for both induction and maintenance). Conclusion For induction of clinical remission, budesonide was more effective than placebo, but less effective than conventional steroids. Budesonide was not effective for the maintenance of remission. Budesonide was safer than conventional steroids, but the long-term effects on the adrenal axis and bone health remain unknown.
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Affiliation(s)
- M Ellen Kuenzig
- CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology Hepatology & Nutrition, Children’s Hospital of Eastern Ontario, Ontario, Ottawa, Canada
| | - Ali Rezaie
- Department of Medicine, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Gilaad G Kaplan
- Department of Medicine, University of Calgary, Calgary, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Canada
| | - Anthony R Otley
- Division of Gastroenterology, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada
| | - A Hillary Steinhart
- Department of Medicine, Division of Gastroenterology, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Anne Marie Griffiths
- Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Eric I Benchimol
- CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology Hepatology & Nutrition, Children’s Hospital of Eastern Ontario, Ontario, Ottawa, Canada
- Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Cynthia H Seow
- Department of Medicine, University of Calgary, Calgary, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Canada
- Correspondence: Cynthia H. Seow, 3280 Hospital Drive NW, TRW building, Rm 6D18, Calgary, AB, T2N 4Z6, Canada, e-mail
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Zhang D, Ma X, Wu H, Hong J, Zhang C, Wu L, Liu J, Zhu Y, Yang L, Wei K, Yan H. Efficacy of herb-partitioned moxibustion at Qihai (CV 6) and bilateral Tianshu (ST 25) on colonic damage and the TLR4/NF-κB signaling pathway in rats with Crohn's disease. J TRADIT CHIN MED 2018. [PMID: 32186061 DOI: 10.1016/j.jtcm.2018.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To observe the effect of stimulating Qihai (CV 6) and bilateral Tianshu (ST 25) with herb-partitioned moxibustion (HPM) in rats with Crohn's disease (CD), and to investigate the possible anti-inflammatory mechanism of HPM. METHODS Forty rats were randomly divided into four groups (n = 10 rats per group): normal control (NC), model control (MC), mesalamine (MES), and HPM. The CD rat model was established in the MC, MES, and HPM groups by administering a mixture of trinitrobenzenesulfonic acid and alcohol via enema. The HPM group received HPM on Qihai (CV 6) and bilateral Tianshu (ST 25), while the MES group received intragastric mesalamine. Colonic histomorphological scores, and serum concentrations of tumor necrosis factor ¦Á (TNF-¦Á) and interleukin 1¦Â (IL-1¦Â) were assessed to evaluate the effects of HPM on colonic reparation and anti-inflammation. The expressions of Toll-like receptor 4 (TLR-4), nuclear factor ¦ÊB inhibitor ¦Á (I¦ÊB-¦Á), I¦ÊB kinase ¦Á/¦Â (IKK¦Á/¦Â), and NF-¦ÊB p65 were further analyzed to investigate the regulatory effects of the interventions on the TLR4/NF-¦ÊB pathway. RESULTS CD rats showed inflammatory colonic damage and increased serum concentrations of TNF-¦Á and IL-1¦Â. The expressions of TLR4, IKK¦Á/¦Â, and NF-¦ÊB p65 in the colons of CD rats were significantly increased compared with the NC group, while the expression of I¦ÊB¦Á (a key negative regulator of NF-¦ÊB p65) was decreased. HPM significantly mitigated colonic damage and reduced the serum concentrations of TNF-α and IL-1¦Â. HPM downregulated the expressions of TLR4, IKK¦Á/¦Â, and NF-¦ÊB p65 in the colon, and upregulated the expression of I¦ÊB¦Á. The effects of HPM in CD rats were similar to those of mesalamine. CONCLUSION HPM alleviates colonic inflammation in CD rats. This may be achieved through regulation of TLR4, which induces NF-¦ÊB signal transduction.
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Affiliation(s)
- Dan Zhang
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Xiaopeng Ma
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Huangan Wu
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Jue Hong
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Cuihong Zhang
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Lingxiang Wu
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Jie Liu
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Yi Zhu
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Ling Yang
- Key Laboratory for Acupuncture-Moxibustion and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China
| | - Kai Wei
- Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Huang Yan
- Department of Acupuncture and Moxibustion, Shanghai Huangpu Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200010, China
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Miehlke S, Acosta MBD, Bouma G, Carpio D, Magro F, Moreels T, Probert C. Oral budesonide in gastrointestinal and liver disease: A practical guide for the clinician. J Gastroenterol Hepatol 2018; 33:1574-1581. [PMID: 29603368 DOI: 10.1111/jgh.14151] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Revised: 02/26/2018] [Accepted: 03/17/2018] [Indexed: 01/10/2023]
Abstract
Oral budesonide is a second-generation steroid that allows local, selective treatment of the gastrointestinal tract and the liver, minimizing systemic exposure. The results of randomized trials comparing budesonide versus placebo or active comparators have led to expert recommendations that budesonide be used to treat mild or moderate active ileocecal Crohn's disease, microscopic colitis (including both collagenous and lymphocytic colitis), ulcerative colitis, and non-cirrhotic autoimmune hepatitis. The mechanism of budesonide action obviates the need for dose tapering due to safety reasons after induction therapy. Where low-dose budesonide is used to maintain remission, usually in microscopic colitis, it does not appear to have adverse safety implications other than slight reductions in cortisol levels on rare occasions. As a gut-selective and liver-selective corticosteroid, budesonide offers an appealing alternative to conventional systemic glucocorticoids in diseases of these organs.
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Affiliation(s)
- Stephan Miehlke
- Center for Digestive Diseases, Internal Medicine Center Eppendorf, Hamburg, Germany
| | - Manuel Barreiro-de Acosta
- Intestinal Inflammatory Disease Unit, Department of Gastroenterology, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Gerd Bouma
- Department of Gastroenterology, Vrije University Medical Center, Amsterdam, The Netherlands
| | - Daniel Carpio
- Digestive System Service, University Hospital of Pontevedra Complex, Pontevedra, Spain
| | - Fernando Magro
- Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- MedInUP, Centre for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal
| | - Tom Moreels
- Hepato-Gastroenterology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Chris Probert
- Department of Gastroenterology, Institute of Translational Medicine, Liverpool, UK
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Yokoyama T, Ohta A, Motoya S, Takazoe M, Yajima T, Date M, Nii M, Nagy P, Suzuki Y, Hibi T. Efficacy and Safety of Oral Budesonide in Patients with Active Crohn's Disease in Japan: A Multicenter, Double-Blind, Randomized, Parallel-Group Phase 3 Study. Inflamm Intest Dis 2017; 2:154-162. [PMID: 29922676 DOI: 10.1159/000484047] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 10/05/2017] [Indexed: 12/13/2022] Open
Abstract
Background US and European guidelines recommend budesonide for the treatment of mild-to-moderate active ileocolic Crohn's disease (CD). However, budesonide has not been approved, and mesalazine is widely used as first-line treatment in Japan. The objective of this study was to evaluate the efficacy and safety of budesonide in patients with mild-to-moderate active CD in Japan. Methods In this phase 3 noninferiority study (NCT01514240), 112 patients with a baseline Crohn's Disease Activity Index (CDAI) score of 180-400 were randomized to budesonide or mesalazine for 8 weeks. Assessments included remission rate (CDAI score ≤150) at weeks 2, 4, and 8, change in CDAI score, health-related quality of life (measured using the Inflammatory Bowel Disease Questionnaire [IBDQ]), and tolerability. Results The remission rate at week 8 was numerically higher in the budesonide group (30.4%) than in the mesalazine group (25.0%), and the noninferiority of budesonide to mesalazine was shown. The mean total CDAI score decreased to a greater extent with budesonide than with mesalazine. Mean IBDQ scores improved from baseline to weeks 2, 4, 8, and 10 in both groups; improvements were numerically higher with budesonide than with mesalazine. No safety concerns were found. Conclusion Budesonide is comparably effective to mesalazine in the treatment of Japanese patients with mild-to-moderate active CD.
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Affiliation(s)
- Tadashi Yokoyama
- Yokoyama Hospital for Gastroenterological Diseases, Nagoya, Japan
| | | | | | | | | | | | | | - Péter Nagy
- AstraZeneca R&D Gothenburg, Mölndal, Sweden
| | - Yasuo Suzuki
- Toho University Sakura Medical Center, Sakura, Japan
| | - Toshifumi Hibi
- Kitasato Institute Hospital, Kitasato University, Tokyo, Japan
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The use of oral corticosteroids in inflammatory bowel diseases in Italy: An IG-IBD survey. Dig Liver Dis 2017; 49:1092-1097. [PMID: 28801181 DOI: 10.1016/j.dld.2017.07.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Revised: 07/06/2017] [Accepted: 07/13/2017] [Indexed: 12/11/2022]
Abstract
AIM To evaluate how Italian gastroenterologists use corticosteroids in clinical practice for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). MATERIAL AND METHODS All members of the Italian Group for Inflammatory Bowel Disease (IG-IBD) were invited to fill in a web-based questionnaire. RESULTS 131/448 (29.2%) members completed the survey. In mild-to-moderate UC and CD relapses, low-bioavailability steroids (LBS) are first-line therapy for 37% and 42% of clinicians, respectively. In case of failure, immediate step-up to biologics or immunosuppressants is considered by 23% and 29%. Regarding conventional corticosteroids (CCS), a fixed starting dose is prescribed by 50%, and a weight-based dose by 22%. Tapering is started after 7-10days by 41% and after 14days by 32%. The preferred tapering schedule is 5mg/week. In case of CCS failure, 47% switch to parenteral steroids before considering shifting to different drug classes. In case of symptoms recurrence during tapering, 14% re-increase the dose and try tapering again. Before prescribing steroids, 72% do not prescribe any specific evaluation whereas during treatment some evaluation is performed by 85%. Vitamin D and calcium supplements are routinely prescribed along with steroids by 38%. CONCLUSIONS Several discrepancies and some deviation from the available guidelines were recorded among Italian gastroenterologists regarding corticosteroids use in IBD patients.
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Starr AE, Deeke SA, Ning Z, Chiang CK, Zhang X, Mottawea W, Singleton R, Benchimol EI, Wen M, Mack DR, Stintzi A, Figeys D. Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn's disease from UC. Gut 2017; 66:1573-1583. [PMID: 27216938 PMCID: PMC5561380 DOI: 10.1136/gutjnl-2015-310705] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 03/10/2016] [Accepted: 04/25/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Accurate differentiation between Crohn's disease (CD) and UC is important to ensure early and appropriate therapeutic intervention. We sought to identify proteins that enable differentiation between CD and UC in children with new onset IBD. DESIGN Mucosal biopsies were obtained from children undergoing baseline diagnostic endoscopy prior to therapeutic interventions. Using a super-stable isotope labeling with amino acids in cell culture (SILAC)-based approach, the proteomes of 99 paediatric control and biopsies of patients with CD and UC were compared. Multivariate analysis of a subset of these (n=50) was applied to identify novel biomarkers, which were validated in a second subset (n=49). RESULTS In the discovery cohort, a panel of five proteins was sufficient to distinguish control from IBD-affected tissue biopsies with an AUC of 1.0 (95% CI 0.99 to 1.0); a second panel of 12 proteins segregated inflamed CD from UC within an AUC of 0.95 (95% CI 0.86 to 1.0). Application of the two panels to the validation cohort resulted in accurate classification of 95.9% (IBD from control) and 80% (CD from UC) of patients. 116 proteins were identified to have correlation with the severity of disease, four of which were components of the two panels, including visfatin and metallothionein-2. CONCLUSIONS This study has identified two panels of candidate biomarkers for the diagnosis of IBD and the differentiation of IBD subtypes to guide appropriate therapeutic interventions in paediatric patients.
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Affiliation(s)
- Amanda E Starr
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Shelley A Deeke
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Zhibin Ning
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Cheng-Kang Chiang
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Xu Zhang
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Walid Mottawea
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada,Department of Microbiology and Immunology, Mansoura University, Mansoura, Egypt
| | - Ruth Singleton
- Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Eric I Benchimol
- Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada,Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada,School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Ming Wen
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - David R Mack
- Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada,Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
| | - Alain Stintzi
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Daniel Figeys
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada,Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada
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Reply. Inflamm Bowel Dis 2017; 23:E23-E24. [PMID: 28426461 DOI: 10.1097/mib.0000000000001125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Comparative Effectiveness of Mesalamine, Sulfasalazine, Corticosteroids, and Budesonide for the Induction of Remission in Crohn's Disease: A Bayesian Network Meta-analysis: Republished. Inflamm Bowel Dis 2017; 23:E26-E37. [PMID: 30052985 DOI: 10.1097/mib.0000000000001158] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 12/13/2016] [Indexed: 01/14/2023]
Abstract
BACKGROUND Induction treatment of mild-to-moderate Crohn's disease is controversial. PURPOSE To compare the induction of remission between different doses of mesalamine, sulfasalazine, corticosteroids, and budesonide for active Crohn's disease. DATA SOURCES We identified randomized controlled trials from existing Cochrane reviews and an updated literature search in Medline, EMBASE, and CENTRAL to November 2015. STUDY SELECTION We included randomized controlled trials (n = 22) in adult patients with Crohn's disease that compared budesonide, sulfasalazine, mesalamine, or corticosteroids with placebo or each other, for the induction of remission (8-17 wks). Mesalamine (above and below 2.4 g/d) and budesonide (above and below 6 mg/d) were stratified into low and high doses. DATA EXTRACTION Our primary outcome was remission, defined as a Crohn's Disease Activity Index score <150. A Bayesian random-effects network meta-analysis was performed on the proportion in remission. DATA SYNTHESIS Corticosteroids (odds ratio [OR] = 3.64; 95% credible interval [CrI]: 2.16-6.19), high-dose budesonide (OR = 2.99; 95% CrI: 1.83-4.90), and high-dose mesalamine (OR = 1.87; 95% CrI: 1.14-3.15) were superior to placebo. Corticosteroids were similar to high-dose budesonide (OR = 1.21; 95% CrI: 0.79-1.89), but more effective than high-dose mesalamine (OR = 1.95; 95% CrI: 1.14-3.25). Sulfasalazine was not significantly superior to any therapy including placebo. LIMITATIONS Randomized controlled trials that use a strict definition of induction of remission and disease severity at enrollment to assess effectiveness in treating mild-to-moderate Crohn's disease are limited. CONCLUSIONS Corticosteroids and high-dose budesonide were effective treatments for inducing remission in mild-to-moderate Crohn's disease. High-dose mesalamine maybe an option among patients preferring to avoid steroids.
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Lee MJ, Heywood N, Sagar PM, Brown SR, Fearnhead NS. Association of Coloproctology of Great Britain and Ireland consensus exercise on surgical management of fistulating perianal Crohn's disease. Colorectal Dis 2017; 19:418-429. [PMID: 28387062 DOI: 10.1111/codi.13672] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 01/04/2017] [Indexed: 02/08/2023]
Abstract
AIM Management of fistulating perianal Crohn's disease (fpCD) is a significant challenge for a colorectal surgeon. A recent survey of surgical practice in this condition showed variation in management approaches. As a result we set out to devise recommendations for practice for UK colorectal surgeons. METHOD Results from a national survey were used to devise a set of potential consensus statements. Consultant colorectal surgeons were invited to participate in the exercise via the previous survey and the mailing list of the professional society. Iterative voting was performed on each statement using a five-point Likert scale and electronic voting, with opportunity for discussion and refinement between each vote. Consensus was defined as > 80% agreement. RESULTS Seventeen surgeons and two patient representatives voted upon 51 statements. Consensus was achieved on 39 items. Participants advocated a patient-centred approach by a colorectal specialist, within strong multidisciplinary teamworking. The use of anti-TNFα therapy is advocated. Where definitive surgical techniques are considered they should be carefully selected to avoid adverse impact on function. Ano/rectovaginal fistulas should be managed by specialists in fistulating disease. Stoma or proctectomy could be discussed earlier in a patient's treatment pathway to improve choice, as they may improve quality of life. CONCLUSION This consensus provides principles and guidance for best practice in managing patients with fpCD.
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Affiliation(s)
- M J Lee
- Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.,Department of General Surgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - N Heywood
- University Hospital South Manchester, Manchester, UK
| | - P M Sagar
- St James University Hospital, Leeds, UK
| | - S R Brown
- Department of General Surgery, Sheffield Teaching Hospitals, Sheffield, UK
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