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Yanofsky R, Rubin DT. A practical approach to positioning therapies in ulcerative colitis. J Can Assoc Gastroenterol 2025; 8:S6-S14. [PMID: 39990515 PMCID: PMC11842905 DOI: 10.1093/jcag/gwae058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/25/2025] Open
Abstract
The therapeutic landscape of ulcerative colitis (UC) has undergone significant change over the last 2 decades. While there are multiple new therapies for the management of UC, long-term remission rates remain low, and this may be in part due to the difficulty of navigating a successful treatment strategy. In this review, we propose a rational framework for treatment selection, sequencing, and optimization in patients with UC. We outline treatment goals and targets for UC, followed by a discussion of the challenges in treatment selection and considerations to help guide a sequencing strategy. These include an assessment of a therapy's efficacy and safety, the convenience in the delivery of the therapy, ease of access, and patient-related factors. We then provide an overview of the currently approved therapies for UC, with an in-depth analysis of their advantages and disadvantages. Finally, we conclude with future directions in the management of UC, which include the use of naturopathic therapies, faecal microbiota therapy, the use of precision medicine, and other strategies such as combination therapy.
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Affiliation(s)
- Russell Yanofsky
- The University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, United States
| | - David T Rubin
- The University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, United States
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Akyüz F, An YK, Begun J, Aniwan S, Bui HH, Chan W, Choi CH, Chopdat N, Connor SJ, Desai D, Flanagan E, Kobayashi T, Lai AYH, Leong RW, Leow AHR, Leung WK, Limsrivilai J, Muzellina VN, Peddi K, Ran Z, Wei SC, Sollano J, Teo MMH, Wu K, Ye BD, Ooi CJ. Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition. Intest Res 2025; 23:37-55. [PMID: 39492666 PMCID: PMC11834365 DOI: 10.5217/ir.2024.00089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/08/2024] [Accepted: 08/09/2024] [Indexed: 11/05/2024] Open
Abstract
The lack of clear definition and classification for "moderate ulcerative colitis (UC)" creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.
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Affiliation(s)
- Filiz Akyüz
- Department of Gastroenterology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Yoon Kyo An
- Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Australia
| | - Jakob Begun
- Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Australia
| | - Satimai Aniwan
- Division of Gastroenterology, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Huu Hoang Bui
- Department of Gastroenterology, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Webber Chan
- The Gastroenterology Group, Gleneagles Hospital, Singapore
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Nazeer Chopdat
- Department of Gastroenterology, Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa
| | - Susan J Connor
- Department of Gastroenterology, Liverpool Hospital, Sydney, Australia
- South Western Clinical School, University of New South Wales, Sydney, Australia
| | - Devendra Desai
- Division of Medical Gastroenterology, P. D. Hinduja Hospital, Mumbai, India
| | - Emma Flanagan
- Department of Gastroenterology, St. Vincent’s Hospital, Melbourne, Australia
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Allen Yu-Hung Lai
- Global Health Program, College of Public Health, National Taiwan University, Taipei, Taiwan
- Ferring Pharmaceuticals, Singapore
| | - Rupert W Leong
- Department of Gastroenterology, Concord Hospital, Sydney, Australia
| | | | - Wai Keung Leung
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - Julajak Limsrivilai
- Deparment of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Virly Nanda Muzellina
- Gastrointestinal Endoscopy Center, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
- Universitas Indonesia, Jakarta, Indonesia
| | - Kiran Peddi
- Department of Gastroenterology, Yashoda Hospital, Hyderabad, India
| | - Zhihua Ran
- Department of Gastroenterology, Zhoupu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jose Sollano
- Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines
| | | | - Kaichun Wu
- Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Baydoun ZA, Rao M, Khan I. Endoplasmic Reticular Stress and Pathogenesis of Experimental Colitis: Mechanism of Action of 5-Amino Salicylic Acid. Med Princ Pract 2024; 34:39-47. [PMID: 39496247 PMCID: PMC11805548 DOI: 10.1159/000541791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 10/02/2024] [Indexed: 11/06/2024] Open
Abstract
OBJECTIVES Inflammatory bowel diseases which are characterized by endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) signaling pathway are commonly treated with 5-amino salicylic acid (5-ASA). The objective of this study was to investigate the role of 5-amino salicylic acid in the UPR-signaling pathway in experimental colitis. MATERIALS AND METHODS Colitis was induced in male Sprague-Dawley rats by intrarectal instillation of trinitrobenzene sulfonic acid. Animals received 5-amino salicylic acid (100 mg/kg body weight) 2 h before the induction of colitis and repeated daily until day 7. The animals were sacrificed on day 7 and tissues were collected for analysis. RESULTS The expression of protein kinase R (PKR)-like ER kinase (PERK), a mediator of UPR signaling increased significantly (p < 0.05), while inositol-requiring enzyme type-1 (IRE1) and the CCAAT/enhancer-binding homologous protein (CHOP) remained unaltered in the inflamed colon. The expression of glucose-regulated protein-78, activator of transcription factor-4, and phosphorylated-eukaryotic initiation factor-2α (eIF2αP) increased (p < 0.05) in the inflamed colon. However, the levels of eIF2α protein and mRNA expression remained unchanged. Myeloperoxidase activity, colon weight, and infiltration of inflammatory cells increased significantly (p < 0.05) in the submucosa whereas the body weight decreased. These changes were significantly inhibited by 5-amino salicylate treatment. CONCLUSION These findings suggest that the anti-inflammatory properties of 5-amino salicylic acid are mediated through the inhibition of the PERK signaling pathway. OBJECTIVES Inflammatory bowel diseases which are characterized by endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) signaling pathway are commonly treated with 5-amino salicylic acid (5-ASA). The objective of this study was to investigate the role of 5-amino salicylic acid in the UPR-signaling pathway in experimental colitis. MATERIALS AND METHODS Colitis was induced in male Sprague-Dawley rats by intrarectal instillation of trinitrobenzene sulfonic acid. Animals received 5-amino salicylic acid (100 mg/kg body weight) 2 h before the induction of colitis and repeated daily until day 7. The animals were sacrificed on day 7 and tissues were collected for analysis. RESULTS The expression of protein kinase R (PKR)-like ER kinase (PERK), a mediator of UPR signaling increased significantly (p < 0.05), while inositol-requiring enzyme type-1 (IRE1) and the CCAAT/enhancer-binding homologous protein (CHOP) remained unaltered in the inflamed colon. The expression of glucose-regulated protein-78, activator of transcription factor-4, and phosphorylated-eukaryotic initiation factor-2α (eIF2αP) increased (p < 0.05) in the inflamed colon. However, the levels of eIF2α protein and mRNA expression remained unchanged. Myeloperoxidase activity, colon weight, and infiltration of inflammatory cells increased significantly (p < 0.05) in the submucosa whereas the body weight decreased. These changes were significantly inhibited by 5-amino salicylate treatment. CONCLUSION These findings suggest that the anti-inflammatory properties of 5-amino salicylic acid are mediated through the inhibition of the PERK signaling pathway.
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Affiliation(s)
- Zahraa A. Baydoun
- Department of Biochemistry, College of Medicine, Kuwait University, Kuwait City, Kuwait
| | - Muddanna Rao
- Department of Anatomy, College of Medicine, Kuwait University, Kuwait City, Kuwait
| | - Islam Khan
- Department of Biochemistry, College of Medicine, Kuwait University, Kuwait City, Kuwait
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Saadah OI, AlAmeel T, Al Sarkhy A, Hasosah M, Al-Hussaini A, Almadi MA, Al-Bawardy B, Altuwaijri TA, AlEdreesi M, Bakkari SA, Alharbi OR, Azzam NA, Almutairdi A, Alenzi KA, Al-Omari BA, Almudaiheem HY, Al-Jedai AH, Mosli MH. Saudi consensus guidance for the diagnosis and management of inflammatory bowel disease in children and adolescents. Saudi J Gastroenterol 2024:00936815-990000000-00101. [PMID: 39215473 DOI: 10.4103/sjg.sjg_171_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 07/20/2024] [Indexed: 09/04/2024] Open
Abstract
ABSTRACT The management of inflammatory bowel disease (IBD) in children and adolescents is challenging. Clear evidence-based guidelines are required for this population. This article provides recommendations for managing IBD in Saudi children and adolescents aged 6-19 years, developed by the Saudi Ministry of Health in collaboration with the Saudi Society of Clinical Pharmacy and the Saudi Gastroenterology Association. All 57 guideline statements are based on the most up-to-date information for the diagnosis and management of pediatric IBD.
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Affiliation(s)
- Omar I Saadah
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Turki AlAmeel
- Department of Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Ahmed Al Sarkhy
- Gastroenterology Unit, Pediatrics Department, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Hasosah
- Department of Pediatrics, Gastroenterology Unit, King Abdulaziz Medical City, National Guard Hospital, Jeddah, Saudi Arabia
- Department of Pediatric Gastroenterology, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- Department of Pediatric Gastroenterology, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Abdulrahman Al-Hussaini
- Children's Specialized Hospital, King Fahad Medical City, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Majid A Almadi
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Badr Al-Bawardy
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Talal A Altuwaijri
- Department of Surgery, Division of Vascular Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed AlEdreesi
- Gastroenterology Unit, Pediatric Department, Al Habib Medical Group, Khobar, Saudi Arabia
| | - Shakir A Bakkari
- Department of Gastroenterology, King Saud Medical City, Riyadh, Saudi Arabia
| | - Othman R Alharbi
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Nahla A Azzam
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Abdulelah Almutairdi
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Alfaisal University, Riyadh, Saudi Arabia
| | - Khalidah A Alenzi
- Executive Management of Transformation, Planning, and Business Development, Tabuk Health Cluster, Tabuk, Saudi Arabia
| | - Bedor A Al-Omari
- Department of Pharmaceutical Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | | | - Ahmed H Al-Jedai
- Deputyship of Therapeutic Affairs, Ministry of Health, Riyadh, Saudi Arabia
- Colleges of Medicine and Pharmacy, Alfaisal University, Riyadh, Saudi Arabia
| | - Mahmoud H Mosli
- Department of Internal Medicine, King Abdulaziz University, Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
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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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Battat R, Chang JT, Loftus EV, Sands BE. IBD Matchmaking - Rational Combination Therapy. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00633-5. [PMID: 39025253 DOI: 10.1016/j.cgh.2024.05.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 05/28/2024] [Accepted: 05/31/2024] [Indexed: 07/20/2024]
Abstract
A growing number of patients with Crohn's disease and ulcerative colitis have disease that is refractory to multiple advanced therapies, have undergone multiple surgeries, and require further treatment options. For this reason, there has been increasing use of multiple simultaneous advanced targeted therapies. Although the knowledge on combined advanced targeted therapy (CATT) in inflammatory bowel disease (IBD) has been largely limited to observational data and early-phase randomized controlled trials, combination of therapies is commonplace in many other diseases. This review discusses conceptual frameworks of CATT in IBD, provides context of combined therapies in other diseases, provides current evidence for CATT in IBD, and projects future applications and positioning of CATT using existing, novel, and orthogonal mechanisms of action. CATT aims to address the need to overcome low efficacy rates and frequent loss of response of current individual therapies. Both treatment exposure and disease duration are major determinants of response to therapy. Identification of safe and effective CATT may impact positioning of this strategy to apply to a broader IBD population.
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Affiliation(s)
- Robert Battat
- Division of Gastroenterology, Centre Hospitalier de l'Université de Montreal, Montreal, Quebec, Canada
| | - John T Chang
- Department of Medicine, University of California San Diego, La Jolla, California; Department of Medicine, Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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D’Amico F, Jairath V, Paridaens K, Peyrin-Biroulet L, Danese S. Drug Optimization in Patients with Mild-to-Moderate Ulcerative Colitis: A Global Survey. J Clin Med 2024; 13:2510. [PMID: 38731039 PMCID: PMC11084860 DOI: 10.3390/jcm13092510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
Background/Objectives: The treatment of patients with mild-to-moderate ulcerative colitis (UC) is challenging. Although there are commonly used guidelines, therapy optimization is not standardized. We conducted a survey to investigate the management and treatment of patients with mild-to-moderate UC. Methods: Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between June and July 2023. The survey addressed various issues of patient care such as patient monitoring, treatment optimization, follow-up, treatment decision making, and therapy de-escalation. Results: The survey included 222 physicians (59.9% men; mean age = 50.4 years) from 66 countries worldwide. Gastroenterologists were the most represented specialists (89.6%), followed by surgeons (3.2%), and internal medicine doctors (2.7%). Two-thirds of the participants (66.7%) had >10 years of experience in the field of IBD. The combination of oral (≥4 g/day) and rectal 5-aminosalicylic acid (5-ASA) was the preferred choice when optimizing therapy. Budesonide MMX (41.8%) and systemic steroids (39.9%) were preferred in patients who failed 5-ASA. Treatment decisions were predominantly based on endoscopic (99.0%) or clinical (59.8%) activity. A significant percentage of clinicians did not optimize therapy in the case of increased fecal calprotectin alone (45.1%) or radiological/ultrasound activity (39.8%) alone. Conclusions: The guidelines for the management of mild-to-moderate UC are well accepted in clinical practice. Endoscopic remission remains the main therapeutic target, followed by clinical remission. Fecal calprotectin and intestinal ultrasound still elicit complaints from physicians.
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Affiliation(s)
- Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, 20132 Milan, Italy;
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Western University, London, CA 91766, Canada;
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France;
- Inserm, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré—Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, 20132 Milan, Italy;
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9
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D'Amico F, Fasulo E, Jairath V, Paridaens K, Peyrin-Biroulet L, Danese S. Management and treatment optimization of patients with mild to moderate ulcerative colitis. Expert Rev Clin Immunol 2024; 20:277-290. [PMID: 38059454 DOI: 10.1080/1744666x.2023.2292768] [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: 10/01/2023] [Accepted: 12/05/2023] [Indexed: 12/08/2023]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a significant health-care burden worldwide. While medical therapy aims to induce and maintain remission, optimal management of mild to moderate UC remains challenging due to heterogeneity in severity classifications and non-standardized approaches. This comprehensive review summarizes current evidence and knowledge gaps to optimize clinical decision-making in patients with mild to moderate UC. AREAS COVERED After an extensive literature search of PubMed, Medline, and Embase through August 2023, we provide an overview of definitions utilized to characterize mild to moderate UC severity and established therapeutic targets. Current medical treatments including mesalazine formulations, corticosteroids, and their combinations are surveyed. The role of emerging intestinal ultrasound, telemedicine, and home testing is explored. Individualized, patient-centered paradigms aiming to streamline care delivery through proactive identification of relapses are also examined. EXPERT OPINION Addressing inconsistencies in disease activity stratification will better align tailored regimens with each patient's profile. Advancing noninvasive technologies like ultrasound criteria and home testing could improve UC management by enabling personalized models. Realizing individualized plans through informed shared-decision making between health-care providers and fully engaged patients holds promise to maximize quality of life outcomes. Continuous improvement relies on innovation bridging different domains to overcome current limitations and push the field toward more predictive and tailored care.
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Affiliation(s)
- Ferdinando D'Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Ernesto Fasulo
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Nancy, France
- INSERM, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Nancy, France
- FHU-CURE, Nancy University Hospital, Nancy, France
- Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD center, Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
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Murphy W, Liu S, Javadiyan S, Vyskocil E, Feizi S, Callejas C, Wormald PJ, Vreugde S, Psaltis AJ. An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells. Int J Mol Sci 2024; 25:2796. [PMID: 38474043 DOI: 10.3390/ijms25052796] [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: 02/02/2024] [Revised: 02/23/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.
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Affiliation(s)
- William Murphy
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia
- The Department of Surgery, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, Australia
| | - Sha Liu
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia
- The Department of Surgery, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, Australia
| | - Shari Javadiyan
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia
- The Department of Surgery, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, Australia
| | - Erich Vyskocil
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia
- Department of Otolaryngology, Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria
| | - Sholeh Feizi
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia
- The Department of Surgery, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, Australia
| | - Claudio Callejas
- Department of Otolaryngology, Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA
- Department of Otolaryngology, Pontificia Universidad Católica de Chile, Santiago 8320165, Chile
| | - Peter-John Wormald
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia
- The Department of Surgery, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, Australia
| | - Sarah Vreugde
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia
- The Department of Surgery, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, Australia
| | - Alkis J Psaltis
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, Australia
- The Department of Surgery, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, Australia
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11
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Awadhi SA, Alboraie M, Albaba EA, Almutairdi A, Alsaad M, Azzam N, Barakat H, D’Amico F, Danese S, El Kady M, Ghoneim H, Hamoudi W, Jazzar A, Mosli M, Shehab H, Sneineh AA. Treatment of Patients with Mild to Moderate Ulcerative Colitis: A Middle East Expert Consensus. J Clin Med 2023; 12:6929. [PMID: 37959394 PMCID: PMC10650478 DOI: 10.3390/jcm12216929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 10/29/2023] [Accepted: 11/02/2023] [Indexed: 11/15/2023] Open
Abstract
The prevalence of ulcerative colitis (UC) in the Middle East is increasing, impacting the economic and healthcare burden. The management of patients with mild to moderate UC is still a challenge as several factors can affect optimal care, including drug choice, induction and maintenance dose, treatment optimization and de-escalation, therapy duration, monitoring, and safety profile. We conducted an expert consensus to standardize the management of patients with mild to moderate UC. Sixteen experts in inflammatory bowel diseases, through a well-established and accepted Delphi methodology, voted and approved eight statements in order to provide practical guidance to clinicians in the Middle East.
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Affiliation(s)
- Sameer Al Awadhi
- Digestive Diseases Unit, Rashid Hospital, Dubai 003206, United Arab Emirates
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt;
| | - Emad Aldin Albaba
- Department of Medicine, Almana General Hospital, Alkhobar 31952, Saudi Arabia;
| | - Abdulelah Almutairdi
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11564, Saudi Arabia;
| | - Monther Alsaad
- Al Madar Medical Centre, Sharjah P.O. Box 80789, United Arab Emirates;
| | - Nahla Azzam
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Husam Barakat
- Department of Gastroenterology, Yarmouk University, Irbid 21163, Jordan;
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.D.); (S.D.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20132 Milan, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.D.); (S.D.)
| | - Mohamed El Kady
- Department of Medical Pharmacology, Faculty of Medicine, Cairo University, Cairo 11559, Egypt;
| | - Hossam Ghoneim
- Immunology and Allergy Department, Medical Research Institute, Alexandria University, Alexandria 5424041, Egypt;
| | - Waseem Hamoudi
- Internal Medicine Department, Al-Bashir Hospital, Amman 11151, Jordan;
| | - Ahmad Jazzar
- Gastroenterology Division, Sheikh Khalifa Medical City, Abu Dhabi 51900, United Arab Emirates;
| | - Mahmoud Mosli
- Department of Medicine, King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia;
| | - Hany Shehab
- Integrated Clinical and Research Center for Intestinal Disorders (ICRID), Gastroenterology Division, Endemic Medicine Department, Cairo University, Cairo 3725121, Egypt;
| | - Awni Abu Sneineh
- Gastroenterology and Hepatology, University of Jordan, Amman 11942, Jordan;
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12
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Uchiyama K, Takagi T, Mizushima K, Asaeda K, Kubota-Kajiwara M, Sugaya T, Kashiwagi S, Minagawa Y, Hotta Y, Tanaka M, Inoue K, Katada K, Kamada K, Ishikawa T, Yasuda H, Konishi H, Kishimoto M, Naito Y, Itoh Y. Clinical Background Factors as Predictors of the Efficacy of 5-Aminosalicylic Acid Suppositories in Patients with Ulcerative Colitis. Inflamm Intest Dis 2023; 8:84-90. [PMID: 37901338 PMCID: PMC10601951 DOI: 10.1159/000533543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 08/07/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.
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Affiliation(s)
- Kazuhiko Uchiyama
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomohisa Takagi
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Katsura Mizushima
- Department of Human Immunology and Nutrition Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kohei Asaeda
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mariko Kubota-Kajiwara
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Sugaya
- Medical Regulatory Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Saori Kashiwagi
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuki Minagawa
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuma Hotta
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Makoto Tanaka
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ken Inoue
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuhiro Katada
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuhiro Kamada
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Ishikawa
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroaki Yasuda
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hideyuki Konishi
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mitsuo Kishimoto
- Department of Surgical Pathology, Kyoto City Hospital, Kyoto, Japan
| | - Yuji Naito
- Department of Human Immunology and Nutrition Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshito Itoh
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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13
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Abstract
Importance Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, with a prevalence exceeding 400 per 100 000 in North America. Individuals with UC have a lower life expectancy and are at increased risk for colectomy and colorectal cancer. Observations UC impairs quality of life secondary to inflammation of the colon causing chronic diarrhea and rectal bleeding. Extraintestinal manifestations, such as primary sclerosing cholangitis, occur in approximately 27% of patients with UC. People with UC require monitoring of symptoms and biomarkers of inflammation (eg, fecal calprotectin), and require colonoscopy at 8 years from diagnosis for surveillance of dysplasia. Risk stratification by disease location (eg, Montreal Classification) and disease activity (eg, Mayo Score) can guide management of UC. First-line therapy for induction and maintenance of remission of mild to moderate UC is 5-aminosalicylic acid. Moderate to severe UC may require oral corticosteroids for induction of remission as a bridge to medications that sustain remission (biologic monoclonal antibodies against tumor necrosis factor [eg, infliximab], α4β7 integrins [vedolizumab], and interleukin [IL] 12 and IL-23 [ustekinumab]) and oral small molecules that inhibit janus kinase (eg, tofacitinib) or modulate sphingosine-1-phosphate (ozanimod). Despite advances in medical therapies, the highest response to these treatments ranges from 30% to 60% in clinical trials. Within 5 years of diagnosis, approximately 20% of patients with UC are hospitalized and approximately 7% undergo colectomy. The risk of colorectal cancer after 20 years of disease duration is 4.5%, and people with UC have a 1.7-fold higher risk for colorectal cancer compared with the general population. Life expectancy in people with UC is approximately 80.5 years for females and 76.7 years for males, which is approximately 5 years shorter than people without UC. Conclusions and Relevance UC affects approximately 400 of every 100 000 people in North America. An effective treatment for mild to moderate UC is 5-aminosalicylic acid, whereas moderate to severe UC can be treated with advanced therapies that target specific inflammation pathways, including monoclonal antibodies to tumor necrosis factor, α4β7 integrins, and IL-12 and IL-23 cytokines, as well as oral small molecule therapies targeting janus kinase or sphingosine-1-phosphate.
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Affiliation(s)
- Beatriz Gros
- IBD Edinburgh Unit, Western General Hospital, Edinburgh, Scotland
- Department of Gastroenterology and Hepatology, Reina Sofía University Hospital, Córdoba, Spain
| | - Gilaad G Kaplan
- Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
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14
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Li D, Li J, Chen T, Qin X, Pan L, Lin X, Liang W, Wang Q. Injectable Bioadhesive Hydrogels Scavenging ROS and Restoring Mucosal Barrier for Enhanced Ulcerative Colitis Therapy. ACS APPLIED MATERIALS & INTERFACES 2023; 15:38273-38284. [PMID: 37530040 DOI: 10.1021/acsami.3c06693] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/03/2023]
Abstract
Despite the progress in the therapy of ulcerative colitis (UC), long-lasting UC remission can hardly be achieved in the majority of UC patients. The key pathological characteristics of UC include an impaired mucosal barrier and local inflammatory infiltration. Thus, a two-pronged approach aiming at repairing damaged mucosal barrier and scavenging inflammatory mediators simultaneously might hold great potential for long-term remission of UC. A rectal formulation can directly offer preferential and effective drug delivery to inflamed colon. However, regular intestinal peristalsis and frequent diarrhea in UC might cause transient drug retention. Therefore, a bioadhesive hydrogel with strong interaction with intestinal mucosa might be preferable for rectal administration to prolong drug retention. Here, we designed a bioadhesive hydrogel formed by the cross-linking of sulfhydryl chondroitin sulfate and polydopamine (CS-PDA). The presence of PDA would ensure the mucosa-adhesive behavior, and the addition of CS in the hydrogel network was expected to achieve the restoration of the intestinal epithelial barrier. To scavenge the key player (excessive reactive oxygen species, ROS) in inflamed colon, sodium ferulic (SF), a potent ROS inhibitor, was incorporated into the CS-PDA hydrogel. After rectal administration, the SF-loaded CS-PDA hydrogel could adhere to the colonic mucosa to allow prolonged drug retention. Subsequently, sustained SF release could be achieved to persistently scavenge ROS in inflammatory areas. Meanwhile, the presence of CS would promote the restoration of the mucosal barrier. Ultimately, scavenging ROS and restoring the mucosal barrier could be simultaneously achieved via this SF-loaded bioadhesive hydrogel scaffold. Our two-pronged approach might provide new insight for effective UC treatment.
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Affiliation(s)
- Daming Li
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Jiao Li
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Tao Chen
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Xianyan Qin
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Lihua Pan
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Xin Lin
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Wenlang Liang
- Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, China
| | - Qin Wang
- Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, China
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15
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.1) – Februar 2023 – AWMF-Registriernummer: 021-009. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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16
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Paridaens K, Fullarton JR, Travis SPL. Efficacy of oral prolonged-release mesalazine in moderately active ulcerative colitis. JGH Open 2023; 7:516-519. [PMID: 37496812 PMCID: PMC10366489 DOI: 10.1002/jgh3.12935] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 06/05/2023] [Accepted: 06/17/2023] [Indexed: 07/28/2023]
Abstract
New meta-analyses are presented that provide further evidence supporting the effectiveness of oral prolonged-release mesalazine compared to other oral mesalazines as induction therapy in patients with moderately active ulcerative colitis.
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Affiliation(s)
| | | | - Simon P L Travis
- NIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation Trust, John Radcliffe HospitalOxfordUK
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17
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Bahnam P, Hanzel J, Ma C, Zou L, Narula N, Singh S, Kahan B, Jairath V. Most Placebo-Controlled Trials in Inflammatory Bowel Disease were Underpowered Because of Overestimated Drug Efficacy Rates: Results from a Systematic Review of Induction Studies. J Crohns Colitis 2023; 17:404-417. [PMID: 36219564 DOI: 10.1093/ecco-jcc/jjac150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Most pharmaceutical clinical trials for inflammatory bowel disease [IBD] are placebo-controlled and require effect size estimation for a drug relative to placebo. We compared expected effect sizes in sample size calculations [SSCs] to actual effect sizes in IBD clinical trials. METHODS MEDLINE, EMBASE, CENTRAL and the Cochrane library were searched from inception to March 26, 2021, to identify placebo-controlled induction studies for luminal Crohn's disease [CD] and ulcerative colitis [UC] that reported an SSC and a primary endpoint of clinical remission/response. Expected effects were subtracted from actual effects, and interquartile ranges [IQRs] for each corresponding median difference were calculated. Linear regression was used to assess whether placebo or drug event rate misspecifications were responsible for these differences. RESULTS Of eligible studies, 36.9% [55/149] were excluded because of incomplete SSC reporting, yielding 94 studies [46 CD, 48 UC]. Treatment effects were overestimated in CD for remission (-12.6% [IQR: -16.3 to -1.6%]), in UC for remission (-10.2% [IQR: -16.5 to -5.6%]) and in CD for response (-15.3% [IQR: -27.1 to -5.8%]). Differences observed were due to overestimated drug event rates, whereas expected and actual placebo event rates were similar. A meta-regression demonstrated associations between overestimated treatment effect sizes and several trial characteristics: isolated ileal disease, longer CD duration, extensive colitis [UC], single-centre, phase 2 and no endoscopic endpoint component [UC]. CONCLUSION Overestimation of IBD therapy efficacy rates resulted in smaller-than-expected treatment effects. These results should be used to inform SSCs and trial design for IBD drug development.
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Affiliation(s)
- Paul Bahnam
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Jurij Hanzel
- Department of Gastroenterology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Alimentiv Inc, London, Ontario, Canada
| | - Christopher Ma
- Alimentiv Inc, London, Ontario, Canada
- Division of Gastroenterology & Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Lily Zou
- Department of Statistics and Actuarial Sciences, University of Waterloo, Waterloo, Ontario, Canada
| | - Neeraj Narula
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | | | - Vipul Jairath
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Alimentiv Inc, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
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18
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Eder P, Łodyga M, Gawron-Kiszka M, Dobrowolska A, Gonciarz M, Hartleb M, Kłopocka M, Małecka-Wojciesko E, Radwan P, Reguła J, Zagórowicz E, Banasiewicz T, Durlik M, Rydzewska G. Guidelines for the management of ulcerative colitis. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. PRZEGLAD GASTROENTEROLOGICZNY 2023; 18:1-42. [PMID: 37007752 PMCID: PMC10050986 DOI: 10.5114/pg.2023.125882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 03/17/2023]
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 2013. It contains 49 recommendations for the diagnosis and treatment, both pharmacological and surgical, of ulcerative colitis 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 of available evidence and the strength of therapeutic recommendations. The degree of expert support for the proposed statements was assessed on a 6-point Likert scale. Voting results, together with comments, are included with each statement.
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Affiliation(s)
- Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan University Clinical Hospital, Poznan, Poland
| | - Michał Łodyga
- Department of Internal Medicine, Faculty of Health Science, Medical University of Warsaw, Warsaw, 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, Poznan University Clinical 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 Nutrition Disorders, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | | | - Piotr Radwan
- Chair and Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Lublin, Poland
| | - Jarosław Reguła
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Edyta Zagórowicz
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Tomasz Banasiewicz
- Department of General, Endocrinological and Gastroenterological Oncology Surgery, Poznan University of Medical Sciences, Poznan University Clinical Hospital, Poznan, Poland
| | - Marek Durlik
- Department of Gastroenterological Surgery and Transplantology, National Medical Institute of Ministry of Inferior and Administration, Warsaw, Poland
| | - Grażyna Rydzewska
- Department of Gastroenterology with the Inflammatory Bowel Disease Subdivision, National Medical Institute of Ministry of Inferior and Administration, Warsaw, Poland
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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19
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Fuxman C, Sicilia B, Linares ME, García-López S, González Sueyro R, González-Lamac Y, Zabana Y, Hinojosa J, Barreiro-de Acosta M, Balderramo D, Balfour D, Bellicoso M, Daffra P, Morelli D, Orsi M, Rausch A, Ruffinengo O, Toro M, Sambuelli A, Novillo A, Gomollón F, De Paula JA. GADECCU 2022 Guideline for the treatment of Ulcerative Colitis. Adaptation and updating of the GETECCU 2020 Guideline. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46 Suppl 1:S1-S56. [PMID: 36731724 DOI: 10.1016/j.gastrohep.2023.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/04/2023] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory disease that compromises the colon, affecting the quality of life of individuals of any age. In practice, there is a wide spectrum of clinical situations. The advances made in the physio pathogenesis of UC have allowed the development of new, more effective and safer therapeutic agents. OBJECTIVES To update and expand the evaluation of the efficacy and safety of relevant treatments for remission induction and maintenance after a mild, moderate or severe flare of UC. RECIPIENTS Gastroenterologists, coloproctologists, general practitioners, family physicians and others health professionals, interested in the treatment of UC. METHODOLOGY GADECCU authorities obtained authorization from GETECCU to adapt and update the GETECCU 2020 Guide for the treatment of UC. Prepared with GRADE methodology. A team was formed that included authors, a panel of experts, a nurse and a patient, methodological experts, and external reviewers. GRADE methodology was used with the new information. RESULTS A 118-page document was prepared with the 44 GADECCU 2022 recommendations, for different clinical situations and therapeutic options, according to levels of evidence. A section was added with the new molecules that are about to be available. CONCLUSIONS This guideline has been made in order to facilitate decision-making regarding the treatment of UC, adapting and updating the guide prepared by GETECCU in the year 2020.
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Affiliation(s)
- Claudia Fuxman
- Servicio de Gastroenterología, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
| | - Beatriz Sicilia
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Burgos, Burgos, España
| | - María Eugenia Linares
- Servicio de Gastroenterología, Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Santiago García-López
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, España
| | - Ramiro González Sueyro
- Servicio de Gastroenterología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Yago González-Lamac
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Mútua Terrassa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España
| | - Joaquín Hinojosa
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital de Manise, Valencia, España
| | - Manuel Barreiro-de Acosta
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, España
| | - Domingo Balderramo
- Servicio de Gastroenterología, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Deborah Balfour
- Unidad de Enfermedades Inflamatorias, HIGEA Clínica de Gastroenterología, Mendoza, Argentina
| | - Maricel Bellicoso
- Área de Gastroenterología, Inmunología Buenos Aires, Buenos Aires, Argentina
| | - Pamela Daffra
- Servicio de Gastroenterología, Hospital Central de Mendoza, Mendoza, Argentina
| | - Daniela Morelli
- Departamento de Educación, Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
| | - Marina Orsi
- Servicio de Gastroenterología Pediátrica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Astrid Rausch
- Servicio de Gastroenterología, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
| | - Orlando Ruffinengo
- Servicio de Gastroenterología, Hospital Provincial del Centenario, Rosario, Argentina
| | - Martín Toro
- Unidad de Enfermedades Inflamatorias, HIGEA Clínica de Gastroenterología, Mendoza, Argentina
| | - Alicia Sambuelli
- Sección de Enfermedades Inflamatorias Intestinales, Hospital Bonorino Udaondo, Buenos Aires, Argentina
| | - Abel Novillo
- Servicio de Gastroenterología, Sanatorio 9 de Julio, Tucumán, Argentina.
| | - Fernando Gomollón
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Instituto de Investigaciones Sanitarias de Aragón, Hospital Clínico Universitario Lozano Blesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestiva (CIBEREHD), Zaragoza, España
| | - Juan Andrés De Paula
- Servicio de Gastroenterología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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Blue light irradiation alleviated dextran sulfate sodium-induced colitis mediated by the Bmal1 pathway in macrophages. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY 2022. [DOI: 10.1016/j.jpap.2022.100156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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21
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Caron B, Jairath V, D’Amico F, Paridaens K, Magro F, Danese S, Peyrin‐Biroulet L. Definition of mild to moderate ulcerative colitis in clinical trials: A systematic literature review. United European Gastroenterol J 2022; 10:854-867. [PMID: 36029157 PMCID: PMC9557958 DOI: 10.1002/ueg2.12283] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 07/15/2022] [Indexed: 11/28/2022] Open
Abstract
We performed a systematic review to investigate the definition of mild to moderate active ulcerative colitis (UC), and to describe predictors of good response to treatment in clinical trials assessing 5-ASA and/or budesonide. Thirty-nine randomized controlled trials were included. The UC Disease Activity Index (UCDAI) was the most frequent score used for defining mild to moderate active UC (16 studies, 41%), followed by Clinical Activity Index in 11 studies (28.2%). Four different cut-offs were used to define mild to moderate active UC using the UCDAI. The most frequently reported predictors of good response to treatment was a mild and moderate disease activity. There is heterogeneity in the definition of mild to moderate active UC in randomized clinical trials. A standardized definition of mild to moderate active UC used for inclusion of patients in clinical trials is needed.
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Affiliation(s)
- Bénédicte Caron
- Department of Gastroenterology and Inserm NGERE U1256Nancy University HospitalUniversity of LorraineNancyFrance
| | - Vipul Jairath
- Department of MedicineWestern UniversityLondonOntarioCanada
- Department of Epidemiology and BiostatisticsWestern UniversityLondonOntarioCanada
- Alimentiv IncLondonOntarioCanada
| | - Ferdinando D’Amico
- Gastroenterology and EndoscopyIRCCS Ospedale San Raffaele and University Vita‐Salute San Raffaele MilanoMilanItaly
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
| | | | - Fernando Magro
- Department of BiomedicineUnit of Pharmacology and TherapeuticsFaculty of MedicineUniversity of PortoPortoPortugal
- Department of Clinical PharmacologySão João University Hospital Center (CHUSJ)PortoPortugal
- Faculty of Medicine, University of PortoCenter for Health Technology and Services Research (CINTESIS)PortoPortugal
| | - Silvio Danese
- Gastroenterology and EndoscopyIRCCS Ospedale San Raffaele and University Vita‐Salute San Raffaele MilanoMilanItaly
| | - Laurent Peyrin‐Biroulet
- Department of Gastroenterology and Inserm NGERE U1256Nancy University HospitalUniversity of LorraineNancyFrance
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22
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Sood A, Singh A, Mahajan R, Midha V, Bernstein CN, Rubin DT. (Re)Appraising Remission in Ulcerative Colitis. Inflamm Bowel Dis 2022:6653351. [PMID: 35917172 DOI: 10.1093/ibd/izac170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Indexed: 12/09/2022]
Abstract
As the therapeutic targets in ulcerative colitis (UC) shift from control of symptoms to mucosal healing and prevention of disease complications like disability, colectomy, and cancer, the definition of remission has evolved. The current definition of clinical remission is variable and is determined by the clinical context in which it is being used. This results in skepticism and uncertainty about the true meaning of the term "clinical remission." In this review, the authors reexamine the definition of clinical remission and propose a novel approach to define remission in UC.
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Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Charles N Bernstein
- IBD Clinical and Research Centre and Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
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23
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Miyazaki R, Sakurai T, Shimada M, Iwashita Y, Shibuya N, Akita Y, Miyashita H, Maruyama Y, Saruta M. Bowel frequency (night) and urgent defecation are improved by budesonide foam in patients with ulcerative colitis: a retrospective observational study. BMC Gastroenterol 2022; 22:310. [PMID: 35751039 PMCID: PMC9233394 DOI: 10.1186/s12876-022-02388-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 06/16/2022] [Indexed: 01/14/2023] Open
Abstract
Introduction Patients with ulcerative colitis (UC) are known to have a significantly poor quality of life due to bowel frequency (night) and urgent defecation. Budesonide foam is a topical medication that was approved in Japan in 2017 for the treatment of UC. However, its efficacy in the treatment of bowel frequency (night) or urgent defecation is unknown. This study aimed to explore the efficacy of budesonide foam for the alleviation of these symptoms. Methods UC patients who received budesonide foam between December 2017 and January 2020 at the Jikei University School of Medicine in Tokyo were enrolled. The simple clinical colitis activity index (SCCAI) was evaluated at the start of budesonide foam treatment and 2 and 6 weeks later in patients who initially scored ≥ 1 for bowel frequency (night) and urgent defecation, respectively. We also studied the effect of budesonide foam on remaining symptoms in patients who had used 5-aminosalicylic acid (5-ASA) topical treatment, those with SCCAI ≥ 3, and those in remission with residual symptoms (SCCAI 1 or 2). Results Of the 233 enrolled patients, 102 were eligible for the study. In 36 patients with bowel frequency (night) treated with budesonide foam were significantly effective, score in SCCAI decreased from 1.17 ± 0.45 at baseline to 0.53 ± 0.61 at week 2 (p < 0.0001) and 0.17 ± 0.38 at week 6 (p < 0.0001). In 45 patients with urgent defecation score in SCCAI decreased significantly from 1.33 ± 0.52 at baseline to 0.44 ± 0.59 at week 2 (p < 0.0001) and 0.22 ± 0.40 at week 6 (p < 0.0001). Of 22 patients who switched from topical 5-ASA administration to budesonide foam, nine at week 2 (41%) and 11 (50%) at week 6 were improved with no symptoms, and there were no cases of worsened symptoms. No severe side effects associated with budesonide foam were observed. Conclusion Budesonide foam administration significantly improves both bowel frequency (night) and urgent defecation-related UC activity and is also effective for the patients who were refractory to topical 5-ASA administration.
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Affiliation(s)
- Ryosuke Miyazaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Toshiyuki Sakurai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Mariko Shimada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yuko Iwashita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Naoki Shibuya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yoshihiro Akita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Haruna Miyashita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yuki Maruyama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
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24
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Yin J, Wei L, Wang N, Li X, Miao M. Efficacy and safety of adjuvant curcumin therapy in ulcerative colitis: A systematic review and meta-analysis. JOURNAL OF ETHNOPHARMACOLOGY 2022; 289:115041. [PMID: 35091013 DOI: 10.1016/j.jep.2022.115041] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 01/05/2022] [Accepted: 01/23/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Curcumin, an active polyphenol extracted from Traditional Chinese medicine Curcuma longa (turmeric), has shown many health-related benefits and pharmacological effects. Adjuvant curcumin therapy for ulcerative colitis has become increasingly popular, but its efficacy and safety of which is still controversial. The purpose of this study is to evaluate the efficacy and safety of adjuvant curcumin therapy in ulcerative colitis. MATERIALS AND METHODS The Medline, EMBASE, the Cochrane Library, CNKI, VIP, WanFang, and SinoMed databases were searched from inception to June 2021, to identify all randomized controlled clinical trials with adjuvant curcumin therapy in ulcerative colitis. The primary outcomes were clinical and endoscopic remission, and subgroup analyses were also performed. RESULTS Six randomized trials with a total of 385 participants were included in this study. Qualified trials recommended that adjuvant curcumin therapy for ulcerative colitis was effective in inducing clinical remission (RR = 2.10, 95% CI 1.13 to 3.89), but not in clinical improvement (RR = 1.62, 95% CI 1.00 to 2.61), endoscopic remission (RR = 4.17, 95% CI 0.63 to 27.71) or endoscopic improvement (RR = 4.13, 95% CI 0.20 to 87.07). Included studies showed that appropriate dosage, formation, longer duration, and topical medication may have a greater potential advantage. No severe adverse effects had been reported. CONCLUSIONS Available evidence suggested that adjuvant curcumin therapy may be effective for clinical remission in ulcerative colitis patients without causing severe adverse effects. The appropriate methods of administration can achieve better curative effect, which requires further study to verify.
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Affiliation(s)
- Juntao Yin
- Department of Pharmacology, Henan University of Chinese Medicine, Henan, China; Department of Pharmacy, Huaihe Hospital, Henan University, Henan, China.
| | - Lunshou Wei
- Department of Gastroenterology, Huaihe Hospital, Henan University, Henan, China.
| | | | - Xiumin Li
- Department of Pharmacology, Henan University of Chinese Medicine, Henan, China.
| | - Mingsan Miao
- Department of Pharmacology, Henan University of Chinese Medicine, Henan, China; National International Cooperation Base of Chinese Medicine, Henan University of Chinese Medicine, Henan, China.
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25
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Li PH, Tang Y, Wen HZ. Qingchang decoction retention enema may induce clinical and mucosal remission in left-sided ulcerative colitis: A case report. World J Clin Cases 2022; 10:3573-3578. [PMID: 35582052 PMCID: PMC9048555 DOI: 10.12998/wjcc.v10.i11.3573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 01/08/2022] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic autoimmune disease characterized by relapsing-remitting abdominal pain, diarrhea, mucopurulent discharge and rectal bleeding. To date, the etiology of the disease remains unknown; therefore, medical therapy is not yet available. Left-sided UC is mainly treated with oral and topical mesalazine. However, due to its modest clinical effect, endoscopic mucosal remission is not achieved in all patients.
CASE SUMMARY A 44-year-old man presented to Longhua Hospital with a history of left-sided UC for more than 6 years and slight bloody diarrhea over time. Endoscopy suggested hyperemia, edema, and erosive mucosa involving the rectum and sigmoid colon. The Traditional Chinese medicine Qingchang decoction (QCD) enema treatment was initiated once a day combined with a previous standard dose of mesalazine for 8 wk, and rectal bleeding ceased after 4 wk of treatment. Another QCD enema treatment was provided after symptom relapse due to drug withdrawal for nearly 6 mo. At the 2-mo follow-up, the colonoscopy results indicated mucosal healing with no erosion or ulcers.
CONCLUSION The Chinese formula QCD retention enema represents a potential treatment for left-sided UC with predominant rectal bleeding to achieve clinical and mucosal remission.
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Affiliation(s)
- Pei-Han Li
- Department of Gastroenterology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yu Tang
- Department of Basic Medicine, Fudan University, Shanghai 200032, China
| | - Hong-Zhu Wen
- Department of Gastroenterology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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26
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Raine T, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, Bachmann O, Bettenworth D, Chaparro M, Czuber-Dochan W, Eder P, Ellul P, Fidalgo C, Fiorino G, Gionchetti P, Gisbert JP, Gordon H, Hedin C, Holubar S, Iacucci M, Karmiris K, Katsanos K, Kopylov U, Lakatos PL, Lytras T, Lyutakov I, Noor N, Pellino G, Piovani D, Savarino E, Selvaggi F, Verstockt B, Spinelli A, Panis Y, Doherty G. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J Crohns Colitis 2022; 16:2-17. [PMID: 34635919 DOI: 10.1093/ecco-jcc/jjab178] [Citation(s) in RCA: 430] [Impact Index Per Article: 143.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University; IRCCS Humanitas Research Hospital, Milan, Italy
| | - Johan Burisch
- Gastrounit, Medical Division, Hvidovre Hospital; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Torsten Kucharzik
- Department of Gastroenterology, Lüneburg Hospital, University of Hamburg, Lüneburg, Germany
| | - Michel Adamina
- Department of Surgery, Clinic of Visceral and Thoracic Surgery, Cantonal Hospital Winterthur, Zurich, Switzerland
- Department of Biomedical Engineering, Clinical Research and Artificial Intelligence in Surgery, Faculty of Medicine, University of Basel, Allschwil, Switzerland
| | - Vito Annese
- Department of Gastroenterology, Fakeeh University Hospital, Dubai, UAE
| | - Oliver Bachmann
- Department of Internal Medicine I, Siloah St. Trudpert Hospital, Pforzheim; Hannover Medical School, Hannover, Germany
| | - Dominik Bettenworth
- University Hospital Munster, Department of Medicine B - Gastroenterology and Hepatology, Munster, Germany
| | - Maria Chaparro
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Wladyslawa Czuber-Dochan
- King's College London, Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, London, UK
| | - Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Medicine - Poznań University of Medical Sciences; Heliodor Święcicki University Hospital, Poznań, Poland
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - Catarina Fidalgo
- Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal
| | - Gionata Fiorino
- Department of Biomedical Sciences, Humanitas University; IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Paolo Gionchetti
- IBD Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna DIMEC, University of Bologna, Bologna, Italy
| | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - Charlotte Hedin
- Karolinska Institutet, Department of Medicine Solna; Karolinska University Hospital, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden
| | - Stefan Holubar
- Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, NIHR Biomedical Research Centre, University of Birmingham; Division of Gastroenterology, University Hospitals Birmingham NHS Trust, Birmingham, UK
| | | | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Tel-HaShomer Sheba Medical Center, Ramat Gan, and Sackler Medical School, Tel Aviv, Israel
| | - Peter L Lakatos
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC, Canada
- 1st Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Theodore Lytras
- School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Ivan Lyutakov
- Department of Gastroenterology, University Hospital 'Tsaritsa Yoanna - ISUL', Medical University Sofia, Sofia, Bulgaria
| | - Nurulamin Noor
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Universitá degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
- Colorectal Surgery, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University; IRCCS Humanitas Research Hospital, Milan, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Francesco Selvaggi
- Department of Advanced Medical and Surgical Sciences, Universitá degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven; Department of Chronic Diseases, Metabolism and Ageing, TARGID - IBD, Leuven, Belgium
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University; IRCCS Humanitas Research Hospital, Milan, Italy
| | - Yves Panis
- Department of Colorectal Surgery, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy and Université of Paris, France
| | - Glen Doherty
- Department of Gastroenterology and Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
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27
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Paridaens K, Fullarton JR, Travis SPL. Efficacy and safety of oral Pentasa (prolonged-release mesalazine) in mild-to-moderate ulcerative colitis: a systematic review and meta-analysis. Curr Med Res Opin 2021; 37:1891-1900. [PMID: 34404286 DOI: 10.1080/03007995.2021.1968813] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Pentasa (prolonged-release mesalazine [5-ASA]) has been available for >30 years as an effective treatment for mild-to-moderate ulcerative colitis (UC). A systematic literature review and meta-analysis was undertaken to provide an up-to-date evaluation of oral Pentasa efficacy and safety for induction and maintenance of remission. METHODS Literature searches were conducted in PubMed, Embase and Cochrane databases, from inception to 02 December 2020. Unpublished studies were also sourced. Meta-analyses using a random-effects model and Bayesian inference compared Pentasa (tablets, granules, capsules) against placebo and other 5-ASAs. RESULTS Twelve studies involving 3674 patients treated with Pentasa were identified. Pentasa 2-4 g/day was superior to placebo at inducing (absolute risk difference [ARD] at 8 weeks 0.14, 95% CI 0.07‒0.21; p < .001) and maintaining (ARD 6-12 months 0.18, 95% CI 0.04‒0.33; p < .05) remission (clinical/endoscopic). Against other 5-ASAs, Pentasa had similar efficacy for induction (ARD <0.001, 95% CI -0.05‒0.05) and maintenance (ARD 0.01, 95% CI -0.07‒0.08) treatment using randomized controlled trial data. Upon inclusion of real-world study data, Pentasa was significantly better at maintaining remission compared both to Eudragit-S mesalazine and sulfasalazine (ARD 0.04, 95% CI 0.02‒0.06; p < .001). Pentasa (1-4 g/day) had similar treatment-related adverse event rates to placebo (ARD 0.02, 95% CI -0.03‒0.06) and Eudragit-L/S mesalazines (2.25-3 vs 2.4-3 g/day, respectively; ARD -0.03, 95% CI -0.12‒0.05), but was better tolerated than sulfasalazine (3 g/day) (ARD 0.07, 95% CI 0.003‒0.14; p < .05). CONCLUSION This study confirms oral Pentasa is efficacious and well-tolerated in treating active UC and maintaining remission. The availability of multiple forms of Pentasa supports physicians' ability to individualize treatment and optimize dosing to improve outcomes.
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Affiliation(s)
| | | | - Simon P L Travis
- NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
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Akbar A, Arnott I, Kennedy NA, Nolan J, Peake S, Whiteoak SR, Probert C, Fraser A, Cheshire A, Lewis A, Sugrue K, Laird S, Scott G. Recommendations for the optimal use of mesalazine in the management of patients with mild to moderate ulcerative colitis. Br J Hosp Med (Lond) 2021; 82:1-11. [PMID: 34726945 DOI: 10.12968/hmed.2021.0399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The 2021 National report from IBD UK included responses from over 10 000 patients with inflammatory bowel disease, over 70% of whom reported having at least one flare in the last 12 months. As the first-line treatment for patients with mild and moderate ulcerative colitis, the action and delivery mechanisms of mesalazine are crucial for successful management of the disease. The choice of the most appropriate formulation of mesalazine and securing patient concordance and adherence to treatment remains a challenge for healthcare professionals. This article details the outcome of a roundtable discussion involving a group of gastroenterology consultants and specialist nurses which considered the importance of ensuring that patients have individualised mesalazine therapy before escalation to other treatments and gives recommendations for the management of patients with mild or moderate ulcerative colitis.
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Affiliation(s)
- Ayesha Akbar
- Consultant Gastroenterologist, St Marks Hospital, Harrow, Middlesex, UK
| | - Ian Arnott
- Consultant Gastroenterologist, Western General Hospital, Edinburgh, UK
| | - Nicholas A Kennedy
- Consultant Gastroenterologist, Royal Devon & Exeter Hospital NHS Foundation Trust, Exeter, UK
| | - Jonathan Nolan
- Consultant Gastroenterologist, Kingston Hospital, Kingston Upon Thames, UK
| | - Simon Peake
- Consultant Gastroenterologist, Imperial College Healthcare NHS Trust, London, UK
| | - Simon R Whiteoak
- Consultant Gastroenterologist, University Hospitals Dorset, Bournemouth, UK
| | - Chris Probert
- Professor of Gastroenterology, University of Liverpool, Liverpool, UK
| | - Aileen Fraser
- IBD Advanced Clinical Practitioner, University Hospitals Bristol & Weston, UK
| | - Alex Cheshire
- Day Case Unit/Endoscopy Nurse Team Lead, Queen Mary's Hospital, St George's University Hospital Trust, London, UK
| | - Allyson Lewis
- IBD Specialist Nurse, Royal Gwent Hospital, Newport, UK
| | - Kathleen Sugrue
- Advanced Nurse Practitioner, Mercy University Hospital, Cork, Ireland
| | - Susan Laird
- IBD Clinical Nurse Specialist Team Lead, Queen Elizabeth University Hospital, Glasgow, UK
| | - Glyn Scott
- Consultant Nurse Gastroenterology/Endoscopy/IBD, East Kent Hospital, Canterbury, UK
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Jhundoo HD, Siefen T, Liang A, Schmidt C, Lokhnauth J, Moulari B, Béduneau A, Pellequer Y, Larsen CC, Lamprecht A. Hyaluronic Acid Increases Anti-Inflammatory Efficacy of Rectal 5-Amino Salicylic Acid Administration in a Murine Colitis Model. Biomol Ther (Seoul) 2021; 29:536-544. [PMID: 34059563 PMCID: PMC8411025 DOI: 10.4062/biomolther.2020.227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 04/19/2021] [Accepted: 04/27/2021] [Indexed: 11/05/2022] Open
Abstract
5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone. Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.
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Affiliation(s)
- Henusha D Jhundoo
- Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn 53121, Germany
| | - Tobias Siefen
- Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn 53121, Germany
| | | | | | | | - Brice Moulari
- PEPITE (EA4267) University of Burgundy / Franche-Comté, Besançon 25000, France
| | - Arnaud Béduneau
- PEPITE (EA4267) University of Burgundy / Franche-Comté, Besançon 25000, France
| | - Yann Pellequer
- PEPITE (EA4267) University of Burgundy / Franche-Comté, Besançon 25000, France
| | | | - Alf Lamprecht
- Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn 53121, Germany.,PEPITE (EA4267) University of Burgundy / Franche-Comté, Besançon 25000, France
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30
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Sicilia B, García-López S, González-Lama Y, Zabana Y, Hinojosa J, Gomollón F. GETECCU 2020 guidelines for the treatment of ulcerative colitis. Developed using the GRADE approach. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 43 Suppl 1:1-57. [PMID: 32807301 DOI: 10.1016/j.gastrohep.2020.07.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Since the first edition of the Guidelines was published in 2013, much information has been generated around the treatment of ulcerative colitis, and new drugs and action protocols have been introduced. Clinical practice has changed substantially, warranting new approaches and a comprehensive review and update of the evidence. MATERIAL AND METHODS Once again, we used the GRADE approach, supported by an electronic tool (https://gradepro.org). The clinical scenarios are the same as in the previous version (induction and maintenance in severe and mild-moderate flare-ups), as are the variables and their evaluation. However, in the updated guidelines, three questions have been deleted, 14 added and 30 maintained, making a total of 44 clinical questions. After an exhaustive review of the evidence, the recommendations are now updated. RESULTS Of the 44 questions analysed, no recommendation could be established in two due to the very low quality of the evidence, while in the other 42, based on different degrees of quality of evidence, recommendations were made according to the GRADE system. In 25 of these questions the final recommendation is strongly in favour, in six strongly against, in seven weakly in favour and in four weakly against. According to the scenarios and recommendations, six algorithms are proposed as a simple guide for practical decision-making. CONCLUSIONS The aim of this update of the 2013 guidelines is to provide answers, based on the GRADE approach, to the different questions we ask ourselves daily when deciding the most appropriate treatment for our patients with ulcerative colitis in the different clinical scenarios.
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Affiliation(s)
- Beatriz Sicilia
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Burgos, España
| | - Santiago García-López
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, España.
| | - Yago González-Lama
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo Hospital Universitario Mútua Terrassa Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
| | - Joaquín Hinojosa
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital de Manises, Valencia, España
| | - Fernando Gomollón
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Instituto de Investigaciones Sanitarias de Aragón, Hospital Clínico Universitario Lozano Blesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Zaragoza, España
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31
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Weixler B, Sonnenberg E, Kreis ME. Colitis ulcerosa. COLOPROCTOLOGY 2021. [DOI: 10.1007/s00053-021-00547-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Barberio B, Segal JP, Quraishi MN, Black CJ, Savarino EV, Ford AC. Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-analysis. J Crohns Colitis 2021; 15:1184-1196. [PMID: 33433562 DOI: 10.1093/ecco-jcc/jjab010] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND 5-Aminosalicylates [5-ASAs] are the mainstay of treatment for ulcerative colitis [UC]. The optimum preparation, dose, and route of administration for UC remain unclear. We conducted a network meta-analysis to examine this issue. METHODS We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to December 2020. We included randomised controlled trials [RCTs] comparing oral, topical, or combined oral and topical 5-ASAs, with each other or placebo for induction of remission or prevention of relapse of UC. Results were reported as pooled relative risks [RRs] with 95% confidence intervals [CIs] to summarise effect of each comparison tested, with treatments ranked according to P-score. RESULTS We identified 40 RCTs for induction of remission and 23 for prevention of relapse. Topical mesalazine [P-score 0.99], or oral and topical mesalazine combined [P-score 0.87] ranked first and second for clinical and endoscopic remission combined. Combined therapy ranked first in trials where ≥50% of patients had left-sided/extensive disease, and topical mesalazine first in trials where ≥50% of patients had proctitis/proctosigmoiditis. High-dose [≥3.3 g/day] oral mesalazine ranked third in most analyses, with the most trials and most patients. For relapse of disease activity, combined therapy and high-dose oral mesalazine ranked first and second, with topical mesalazine third. 5-ASAs were safe and well tolerated, regardless of regimen. CONCLUSIONS Our results support previous evidence; however, higher doses of oral mesalazine had more evidence for induction of remission than combined therapy and were significantly more efficacious than lower doses. Future RCTs should better establish the role of combined therapy for induction of remission, as well as optimal doses of oral 5-ASAs to prevent relapse.
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Affiliation(s)
- Brigida Barberio
- Department of Surgery, Oncology and Gastroenterology [DISCOG], Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy
| | - Jonathan P Segal
- Department of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - M Nabil Quraishi
- Department of Gastroenterology, University Hospitals Birmingham, Birmingham, UK.,University of Birmingham Microbiome Treatment Centre, University of Birmingham, UK
| | - Christopher J Black
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Edoardo V Savarino
- Department of Surgery, Oncology and Gastroenterology [DISCOG], Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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33
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Chinese consensus on diagnosis and treatment in inflammatory bowel disease (2018, Beijing). J Dig Dis 2021; 22:298-317. [PMID: 33905603 DOI: 10.1111/1751-2980.12994] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 04/22/2021] [Indexed: 12/11/2022]
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Kobayashi Y, Ohfuji S, Kondo K, Fukushima W, Sasaki S, Kamata N, Yamagami H, Fujiwara Y, Suzuki Y, Hirota Y. Association of Dietary Fatty Acid Intake With the Development of Ulcerative Colitis: A Multicenter Case-Control Study in Japan. Inflamm Bowel Dis 2021; 27:617-628. [PMID: 32507894 DOI: 10.1093/ibd/izaa140] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Dietary fatty acids can affect chronic intestinal inflammation and have been reported to be associated with the development of ulcerative colitis (UC), mainly in Europe and the United States. The association of dietary intake of fatty acids and the risk for UC was investigated in Japan, where dietary habits lead to lower meat and higher fish consumption than in Western countries. METHODS A multicenter case-control study of 83 newly diagnosed patients with UC and 128 age- and sex-matched control patients in the hospital was conducted from 2008 to 2014. Dietary fatty acid intake in the preceding 1 month and 1 year were examined using a self-administered diet history questionnaire that was developed for Japanese people. RESULTS About 92% of patients had experienced the first symptoms of UC within the preceding 11 months. Regarding dietary habits in the preceding year, the risk for UC was significantly decreased in patients who consumed n-6/n-3 polyunsaturated fatty acids at a ratio of ≥5.2 (odds ratio [OR] = 0.26; 95% confidence interval [CI], 0.10-0.68). Conversely, an increased risk for UC was observed in the highest tertiles of consumption of docosahexaenoic acid (OR = 7.22; 95% CI, 2.09-24.95), eicosapentaenoic acid (OR = 6.91; 95% CI, 1.88-25.44), and docosapentaenoic acid (OR = 4.83; 95% CI, 1.56-14.95). CONCLUSIONS The ratio of n-6/n-3 polyunsaturated fatty acid intake was associated with a decreased risk for UC development. However, high intakes of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid may increase the risk for UC development.
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Affiliation(s)
- Yumie Kobayashi
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Satoko Ohfuji
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kyoko Kondo
- Administration Division, Osaka City University Hospital, Osaka, Japan
| | - Wakaba Fukushima
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Satoshi Sasaki
- Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hirokazu Yamagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuo Suzuki
- Department of Internal Medicine, Sakura Medical Center, Toho University, Chiba, Japan
| | - Yoshio Hirota
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan.,College of Healthcare Management, Fukuoka, Japan
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Shen H, Zhang S, Zhao W, Ren S, Ke X, Gu Q, Tang Z, Xie J, Chen S, Chen Y, Zou J, Zhang L, Shen Z, Zheng K, Liu Y, Gu P, Cheng J, Hu J, Zhu L. Randomised clinical trial: Efficacy and safety of Qing-Chang-Hua-Shi granules in a multicenter, randomized, and double-blind clinical trial of patients with moderately active ulcerative colitis. Biomed Pharmacother 2021; 139:111580. [PMID: 33857914 DOI: 10.1016/j.biopha.2021.111580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 03/31/2021] [Accepted: 04/02/2021] [Indexed: 02/07/2023] Open
Abstract
Qing-Chang-Hua-Shi (QCHS) is a Chinese herbal formula, which is composed of 11 herbs. Studies have also shown that QCHS granules can alleviate colitis in animal models by preventing inflammatory responses and suppressing apoptosis through the MEK/ERK signaling pathway. To determine the efficacy and safety of QCHS granules in patients with moderately active UC. We performed a multicenter, randomized, placebo-controlled, double-blind study of patients with moderately active UC who did not respond to 4 weeks of mesalazine therapy at the maximum dose. Patients were randomly assigned to groups and administered QCHS granules (125 g/day, n = 59) or an identical placebo, which was similar to the QCHS granules in color and taste (125 g/day, n = 60), with continued 5-ASA 4 g/d therapy for 12 weeks. The primary outcome was the rate of clinical response and clinical remission at week 12. The secondary outcomes were health-related quality of life, endoscopic response rate, and mucosal healing rate. Any changes in mucus/bloody stool and diarrhea were recorded. Out of the 119 enrolled patients at 10 different centers in China, 102 patients completed the trial. Clinical remission and clinical response were seen in 31.48% and 92.59% of QCHS-treated patients, and 12.50% and 72.92% of placebo-treated patients, respectively. There was a significant difference between the two treatment groups. More patients receiving QCHS granules vs. placebo achieved remission of mucus/bloody stool (70.37% vs. 47.92%, P = 0.0361). Adverse event rates were similar (QCHS granules 38.33%; placebo 25.42%). In conclusion, QCHS granules were superior to the placebo in introducing clinical remission and mucosal healing, as well as in relieving mucus/blood stool in patients with moderately active and 5-ASA-refractory UC.
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Affiliation(s)
- Hong Shen
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Shengsheng Zhang
- Beijing Hospital of Traditional Chinese Medicine, Beijing, China
| | - Wenxia Zhao
- The First Affiliated Hospital of Henan University of CM, Zhengzhou, China
| | - Shunping Ren
- The Hospital of Shanxi University of Chinese Medicine, Taiyuan, China
| | - Xiao Ke
- The Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fuzhou, China
| | - Qinghua Gu
- Nantong Hospital of Traditional Chinese Medicine, Nantong, China
| | - Zhipeng Tang
- LongHua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jingri Xie
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Haerbin, China
| | - Suning Chen
- Shengjing Hospital of China Medicine University, Shenyang, China
| | - Yan Chen
- GuangDong Province Hospital of Chinese Medicine, Guangzhou, China
| | - Jiandong Zou
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Lu Zhang
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Zhaofeng Shen
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Kai Zheng
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Yajun Liu
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Peiqing Gu
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Jiafei Cheng
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Jingyi Hu
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China
| | - Lei Zhu
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China.
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Ran Z, Wu K, Matsuoka K, Jeen YT, Wei SC, Ahuja V, Chen M, Hu PJ, Andoh A, Kim HJ, Yang SK, Watanabe M, Ng SC, Hibi T, Hilmi IN, Suzuki Y, Han DS, Leung WK, Sollano J, Ooi CJ, Qian J. Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia. J Gastroenterol Hepatol 2021; 36:637-645. [PMID: 32672839 DOI: 10.1111/jgh.15185] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 05/05/2020] [Accepted: 05/12/2020] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.
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Affiliation(s)
- Zhihua Ran
- Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Kaichun Wu
- Department of Gastroenterology, Fourth Military Medical University, Xi'an, China
| | - Katsuyoshi Matsuoka
- Department of Gastroenterology, Toho University Sakura Medical Center, Chiba, Japan
| | - Yoon Tae Jeen
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Pin-Jin Hu
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Akira Andoh
- Department of Gastroenterology, Shiga University, Otsu, Japan
| | - Hyo Jong Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University, Tokyo, Japan
| | - Ida Normiha Hilmi
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yasuo Suzuki
- Department of Internal Medicine, Toho University, Sakura, Japan
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Wai Keung Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Hong Kong
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Choon Jin Ooi
- Gleneagles Medical Centre and Duke-NUS Medical School, Singapore
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College, Beijing, China
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37
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Nakase H, Uchino M, Shinzaki S, Matsuura M, Matsuoka K, Kobayashi T, Saruta M, Hirai F, Hata K, Hiraoka S, Esaki M, Sugimoto K, Fuji T, Watanabe K, Nakamura S, Inoue N, Itoh T, Naganuma M, Hisamatsu T, Watanabe M, Miwa H, Enomoto N, Shimosegawa T, Koike K. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J Gastroenterol 2021; 56:489-526. [PMID: 33885977 PMCID: PMC8137635 DOI: 10.1007/s00535-021-01784-1] [Citation(s) in RCA: 251] [Impact Index Per Article: 62.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn's disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.
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Affiliation(s)
- Hiroshi Nakase
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan ,grid.263171.00000 0001 0691 0855Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuoku, Sapporo, Hokkaido 060-8543 Japan
| | - Motoi Uchino
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Shinichiro Shinzaki
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Minoru Matsuura
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Katsuyoshi Matsuoka
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Taku Kobayashi
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Masayuki Saruta
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Fumihito Hirai
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Keisuke Hata
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Sakiko Hiraoka
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Motohiro Esaki
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Ken Sugimoto
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Toshimitsu Fuji
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Kenji Watanabe
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Shiro Nakamura
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Nagamu Inoue
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Toshiyuki Itoh
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Makoto Naganuma
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Tadakazu Hisamatsu
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Mamoru Watanabe
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
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Kucharzik T, Dignass AU, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa – Living Guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:e241-e326. [PMID: 33260237 DOI: 10.1055/a-1296-3444] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Axel U Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Philip Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Klaus Kannengießer
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Andreas Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | | | - Andreas Stallmach
- Gastroenterologie, Hepatologie und Infektiologie, Friedrich Schiller Universität, Jena, Deutschland
| | - Jürgen Stein
- Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt/Main, Deutschland
| | - Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
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Lloyd K, Papoutsopoulou S, Smith E, Stegmaier P, Bergey F, Morris L, Kittner M, England H, Spiller D, White MHR, Duckworth CA, Campbell BJ, Poroikov V, Martins Dos Santos VAP, Kel A, Muller W, Pritchard DM, Probert C, Burkitt MD. Using systems medicine to identify a therapeutic agent with potential for repurposing in inflammatory bowel disease. Dis Model Mech 2020; 13:dmm044040. [PMID: 32958515 PMCID: PMC7710021 DOI: 10.1242/dmm.044040] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 09/08/2020] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) cause significant morbidity and mortality. Aberrant NF-κB signalling is strongly associated with these conditions, and several established drugs influence the NF-κB signalling network to exert their effect. This study aimed to identify drugs that alter NF-κB signalling and could be repositioned for use in IBD. The SysmedIBD Consortium established a novel drug-repurposing pipeline based on a combination of in silico drug discovery and biological assays targeted at demonstrating an impact on NF-κB signalling, and a murine model of IBD. The drug discovery algorithm identified several drugs already established in IBD, including corticosteroids. The highest-ranked drug was the macrolide antibiotic clarithromycin, which has previously been reported to have anti-inflammatory effects in aseptic conditions. The effects of clarithromycin effects were validated in several experiments: it influenced NF-κB-mediated transcription in murine peritoneal macrophages and intestinal enteroids; it suppressed NF-κB protein shuttling in murine reporter enteroids; it suppressed NF-κB (p65) DNA binding in the small intestine of mice exposed to lipopolysaccharide; and it reduced the severity of dextran sulphate sodium-induced colitis in C57BL/6 mice. Clarithromycin also suppressed NF-κB (p65) nuclear translocation in human intestinal enteroids. These findings demonstrate that in silico drug repositioning algorithms can viably be allied to laboratory validation assays in the context of IBD, and that further clinical assessment of clarithromycin in the management of IBD is required.This article has an associated First Person interview with the joint first authors of the paper.
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Affiliation(s)
- Katie Lloyd
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3GE, UK
| | - Stamatia Papoutsopoulou
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3GE, UK
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
| | - Emily Smith
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
| | | | | | | | | | - Hazel England
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
| | - Dave Spiller
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
| | - Mike H R White
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
| | - Carrie A Duckworth
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3GE, UK
| | - Barry J Campbell
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3GE, UK
| | | | | | | | - Werner Muller
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
| | - D Mark Pritchard
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3GE, UK
| | - Chris Probert
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3GE, UK
| | - Michael D Burkitt
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3GE, UK
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
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40
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Kucharzik T, Koletzko S, Kannengiesser K, Dignass A. Ulcerative Colitis-Diagnostic and Therapeutic Algorithms. DEUTSCHES ARZTEBLATT INTERNATIONAL 2020; 117:564-574. [PMID: 33148393 DOI: 10.3238/arztebl.2020.0564] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 03/05/2020] [Accepted: 07/25/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Ulcerative colitis is a chronic inflammatory bowel disease with an estimated 150 000 patients in Germany alone. METHODS This review is based on publications about current diagnostic and therapeutic strategies for ulcerative colitis that were retrieved by a selective search in PubMed, and on current guidelines. RESULTS The primary goal of treatment is endoscopically confirmed healing of the mucosa. Mesalamine, in various forms of administration, remains the standard treatment for uncomplicated ulcerative colitis. Its superiority over placebo has been confirmed in meta-analyses of randomized, controlled trials. Glucocorticoids are highly effective in the acute treatment of ulcerative colitis, but they should only be used over the short term, because of their marked side effects. Further drugs are available to treat patients with a more complicated disease course of ulcerative colitis, including azathioprine, biological agents, JAK inhibitors (among them TNF antibodies, biosimilars, ustekinumab, vedolizumab, and tofacitinib), and calcineurin inhibitors. Proctocolectomy should be considered in refractory cases, or in the presence of high-grade epithelial dysplasia. Ulcerative colitis beginning in childhood or adolescence is often characterized by rapid progression and frequent comorbidities that make its treatment a special challenge. CONCLUSION A wide variety of drugs are now available for the treatment of ulcerative colitis, enabling the individualized choice of the best treatment for each patient. Regular surveillance colonoscopies to rule out colon carcinoma should be scheduled at intervals that depend on risk stratification.
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Affiliation(s)
- Torsten Kucharzik
- Department of General Internal Medicine and Gastroenterology, University Teaching Hospital Lüneburg; Dr. von Hauner Children's Hospital, LMU Klinikum, University of Munich; Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland; Department of Pediatric Gastroenterology, LMU Klinikum, University of Munich; Medical Clinic I, Agaplesion Markus Krankenhaus, Frankfurt/Main
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41
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Kobayashi T, Siegmund B, Le Berre C, Wei SC, Ferrante M, Shen B, Bernstein CN, Danese S, Peyrin-Biroulet L, Hibi T. Ulcerative colitis. Nat Rev Dis Primers 2020; 6:74. [PMID: 32913180 DOI: 10.1038/s41572-020-0205-x] [Citation(s) in RCA: 861] [Impact Index Per Article: 172.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/21/2020] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. UC has evolved into a global burden given its high incidence in developed countries and the substantial increase in incidence in developing countries. An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. Since the early 2000s, anti-tumour necrosis factor (TNF) treatment has significantly improved treatment outcomes. Advances in medical treatments have enabled a paradigm shift in treatment goals from symptomatic relief to endoscopic and histological healing to achieve better long-term outcomes and, consequently, diagnostic modalities have also been improved to monitor disease activity more tightly. Despite these improvements in patient care, a substantial proportion of patients, for example, those who are refractory to medical treatment or those who develop colitis-associated colorectal dysplasia or cancer, still require restorative proctocolectomy. The development of novel drugs and improvement of the treatment strategy by implementing personalized medicine are warranted to achieve optimal disease control. However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.
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Affiliation(s)
- Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
| | - Britta Siegmund
- Division of Gastroenterology, Infectiology and Rheumatology, Charite-Universitatsmedizin, Berlin, Germany
| | - Catherine Le Berre
- Department of Gastroenterology, Nancy University Hospital, Inserm U1256 NGERE, Lorraine University, Lorraine, France
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Bo Shen
- Center for Inflammatory Bowel Diseases, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA
| | - Charles N Bernstein
- University of Manitoba IBD Clinical and Research Centre and Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Silvio Danese
- Humanitas Clinical and Research Center - IRCCS - and Humanitas University, Department of Biomedical Sciences, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Inserm U1256 NGERE, Lorraine University, Lorraine, France
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
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42
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Zheng T, Wang X, Chen Z, He A, Zheng Z, Liu G. Efficacy of adjuvant curcumin therapy in ulcerative colitis: A meta-analysis of randomized controlled trials. J Gastroenterol Hepatol 2020; 35:722-729. [PMID: 31696975 DOI: 10.1111/jgh.14911] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 10/09/2019] [Accepted: 10/13/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Aminosalicylic acids are recognized to be the first-line treatment options for ulcerative colitis. Currently, the effectiveness of curcumin as an adjuvant treatment in ulcerative colitis has been investigated, which was still controversial. This study aimed to systematically review and meta-analyze the efficacy and safety of curcumin as an adjuvant treatment in ulcerative colitis. METHODS The PubMed, EMBASE, and Cochrane Library databases were searched from original to July 2019, and relevant randomized controlled clinical trials were enrolled and analyzed. The primary outcomes were clinical and endoscopic remission; meanwhile, the secondary outcomes were clinical and endoscopic improvement. Subgroup analyses of doses, delivery way, form, and intervention time of curcumin were also conducted. RESULTS Six randomized controlled clinical trials with a total of 349 patients were included. Eligible trials suggested that adjuvant curcumin treatment in ulcerative colitis was effective in inducing clinical remission (odds ratio [OR] = 5.18, 95% confidence interval [CI]: 1.84-14.56, P = 0.002), endoscopic remission (OR = 5.69, 95% CI: 1.28-25.27, P = 0.02), and endoscopic improvement (OR = 17.05, 95% CI: 1.30-233.00, P = 0.03), but not in clinical improvement (OR = 4.79, 95% CI: 1.02-22.43, P = 0.05). We can see the potential advantages in large dosage, topical enema, special drug form, and longer duration from the enrolled studies. There were no severe side effects reported. CONCLUSIONS Curcumin, as an adjuvant treatment of mesalamine, was proved to be effective and safe in ulcerative colitis. Better efficacy can be achieved with suitable dose, delivery way, formation, and intervention time, which needs further study to verify.
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Affiliation(s)
- Ting Zheng
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Xin Wang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Zongran Chen
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Anqi He
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Zicheng Zheng
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Gang Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
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Blackwell J, Selinger C, Raine T, Parkes G, Smith MA, Pollok R. Steroid use and misuse: a key performance indicator in the management of IBD. Frontline Gastroenterol 2020; 12:207-213. [PMID: 33907617 PMCID: PMC8040510 DOI: 10.1136/flgastro-2019-101288] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 03/06/2020] [Accepted: 03/18/2020] [Indexed: 02/04/2023] Open
Abstract
Corticosteroids remain an important tool for inducing remission in inflammatory bowel disease (IBD) but they have no role in maintenance of remission. The significant adverse side effect profile of these drugs means their use should be avoided where possible or measures taken to reduce their risk. Despite an expanding array of alternative therapies, corticosteroid dependency and excess remain common. Appropriate steroid use is now regarded a key performance indicator in the management of IBD. This article aims to outline indications for corticosteroid use in IBD, their risks and strategies to reduce their use and misuse.
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Affiliation(s)
- Jonathan Blackwell
- Department of Gastroenterology, St George's Hospitals NHS Foundation Trust, London, UK
- School of Public Health, Imperial College London, London, UK
| | - Christian Selinger
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- The Leeds Institute of Research at St James’, University of Leeds, Leeds, UK
| | - Tim Raine
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Gareth Parkes
- Department of Gastroenterology, Royal London Hospital, London, UK
| | - Melissa A Smith
- Digestives Diseases Centre, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Department of Gastroenterology, Brighton and Sussex Medical School, Brighton, UK
| | - Richard Pollok
- Department of Gastroenterology, St George's Hospitals NHS Foundation Trust, London, UK
- Division of Infection and Immunity, St George’s University London, London, UK
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44
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Ginard D, Marín-Jiménez I, Barreiro-de Acosta M, Ricart E, Domènech E, Gisbert JP, Esteve M, Mínguez M. Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on topical therapy in ulcerative colitis. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:97-105. [PMID: 31839219 DOI: 10.1016/j.gastrohep.2019.10.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 10/16/2019] [Indexed: 06/10/2023]
Abstract
Although most patients with ulcerative colitis should be given topical treatment, different studies have shown that they are underused in clinical practice. The purpose of this article is to answer 10 specific questions about which drugs are available for topical use in the treatment of ulcerative colitis, and their characteristics in terms of formulation, dosage, presentation, application and proximal distribution of rectal-administered drugs. The efficacy of available topical drugs and the benefits of combining different formulations and routes of administration, and their usefulness during disease remission are evaluated. Finally, a series of recommendations addressed to patients are given on the correct application of topical treatment.
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Affiliation(s)
- Daniel Ginard
- Servicio de Aparato Digestivo, Hospital Universitario Son Espases, Palma, España.
| | - Ignacio Marín-Jiménez
- Servicio de Medicina del Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España
| | - Manuel Barreiro-de Acosta
- Servicio de Aparato Digestivo, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, A Coruña, España
| | - Elena Ricart
- Servicio de Gastroenterología, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - Eugeni Domènech
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, España
| | - Maria Esteve
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Aparato Digestivo, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, España
| | - Miguel Mínguez
- Servicio de Medicina Digestiva, Hospital Clínico de Valencia, Universitat de València, Valencia, España
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45
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Solving the questions regarding 5-aminosalitylate formulation in the treatment of ulcerative colitis. J Gastroenterol 2020; 55:1013-1022. [PMID: 32778960 PMCID: PMC7567706 DOI: 10.1007/s00535-020-01713-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 07/22/2020] [Indexed: 02/04/2023]
Abstract
5-aminosalicylate is a fundamental treatment for patients with ulcerative colitis with mild-to-moderate disease; however, evidence for 5-aminosalicylate treatment is unclear in some situations. This review discusses the clinical guidelines and previous studies, and highlights the following points: (1) Although rectal 5-aminosalicylate is effective for proctitis, physicians should endeavor to reduce patient's distress when administering suppositories or enema as the first-line therapy. It should be clarified whether oral 5-aminosalicylate alone with a drug delivery system that allows higher 5-aminosalicylate concentrations to reach the distal colon would be as effective as rectal 5-aminosalicylate therapy. (2) There has been no direct evidence demonstrating the clinical efficacy of switching the 5-aminosalicylate treatment to other 5-aminosalicylate formulations. However, switching to a different 5-aminosalicylate formulation may be indicated if clinical symptoms are not progressive. (3) Several studies have shown that colonic mucosal 5-aminosalicylate concentration correlates with clinical and endoscopic severity; however, it is unclear whether a high 5-aminosalicylate concentration has therapeutic efficacy. (4) The maximum dose of 5-aminosalicylate is necessary for patients with risk factors for recurrence or hospitalization. (5) Optimization of 5-aminosalicylate dosage may be indicated even for quiescent patients with ulcerative colitis if mucosal healing is not obtained, and if patients have multiple risk factors for recurrence. (6) Furthermore, the discontinuation of 5-aminosalicylate is acceptable when biologics are used. Because there are many "old studies" providing evidence for 5-aminosalicylate formulations, more clinical studies are needed to establish new evidence.
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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: 1452] [Impact Index Per Article: 242.0] [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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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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Baehler C, Brüngger B, Blozik E, Vavricka SR, Schoepfer AM. Real-World Data on Topical Therapies and Annual Health Resource Utilization in Hospitalized Swiss Patients with Ulcerative Colitis. Inflamm Intest Dis 2019; 4:144-153. [PMID: 31768387 DOI: 10.1159/000502205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 07/17/2019] [Indexed: 11/19/2022] Open
Abstract
Objectives Topical treatment with aminosalicylates and/or budesonide was shown to be highly effective in patients with ulcerative colitis (UC), while reducing the likelihood of systemic adverse effects. However, previous research has shown that topical treatment is clearly underused. We aimed to evaluate the use of topical therapy in the real-world setting. Methods This is an observational study based on claims data of 201 Swiss adult patients who were hospitalized for UC between 2012 and 2014 and who were then followed for 1 year. A variety of factors presumably associated with topical treatment were examined. Annual health care utilization (UC-related medications, diagnostic procedures, consultations, and rehospitalizations) of patients with versus without topical therapy was compared. Results Of the 201 hospitalized UC patients, 82 (40.8%) were treated with topical 5-acetylsalicylic acid (ASA) and/or topical rectal steroids. The main factors significantly and positively associated with receiving topical treatment were the use of topical treatment in the year prior to the hospitalization, receiving oral 5-ASA, and living in an urban area. The mode of administration was further related to the language area. Patients with topical therapy significantly more often received other UC-related medications, such as combinations with systemic steroids. They significantly more often underwent colonoscopies and calprotectin measurements, and more often consulted a gastroenterologist in the follow-up, while there was no significant difference regarding rehospitalizations. Conclusions Topical treatment is underused in patients with UC, which stands in contrast to the current European Crohn's and Colitis Organization guidelines. Patients' preferences and considerations need to be taken into account when prescribing medical therapy.
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Affiliation(s)
- Caroline Baehler
- Department of Health Sciences, Helsana Insurance Group, Zurich, Switzerland
| | - Beat Brüngger
- Department of Health Sciences, Helsana Insurance Group, Zurich, Switzerland
| | - Eva Blozik
- Department of Health Sciences, Helsana Insurance Group, Zurich, Switzerland.,Department of Medicine, University Medical Centre Freiburg, Freiburg im Breisgau, Germany
| | - Stephan R Vavricka
- Center for Gastroenterology and Hepatology, Zurich, Switzerland.,Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Alain M Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois/CHUV and University of Lausanne, Lausanne, Switzerland
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Mucosal Metabolomic Profiling and Pathway Analysis Reveal the Metabolic Signature of Ulcerative Colitis. Metabolites 2019; 9:metabo9120291. [PMID: 31783598 PMCID: PMC6950742 DOI: 10.3390/metabo9120291] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/21/2019] [Accepted: 11/25/2019] [Indexed: 12/12/2022] Open
Abstract
The onset of ulcerative colitis (UC) is characterized by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host–microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies. This study aims to explore the mucosal metabolomic profile in UC patients, and to define the UC metabolic signature. Treatment- naïve UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopies. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acyl carnitine, and amino acid profiles. Several pathways were found perturbed according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as tryptophan metabolism) to fatty acid metabolism, namely linoleic and butyrate. These metabolic changes during UC reflect the homeostatic disturbance in the gut, and highlight the importance of system biology approaches to identify key drivers of pathogenesis which prerequisite personalized medicine.
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Diab J, Hansen T, Goll R, Stenlund H, Ahnlund M, Jensen E, Moritz T, Florholmen J, Forsdahl G. Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State. Inflamm Bowel Dis 2019; 25:1780-1787. [PMID: 31077307 DOI: 10.1093/ibd/izz098] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The onset of ulcerative colitis (UC) is associated with alterations in lipid metabolism and a disruption of the balance between pro- and anti-inflammatory molecules. Only a few studies describe the mucosal lipid biosignatures during active UC. Moreover, the dynamics of lipid metabolism in the remission state is poorly defined. Therefore, this study aims to characterize mucosal lipid profiles in treatment-naïve UC patients and deep remission UC patients compared with healthy subjects. METHODS Treatment-naïve UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission defined by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified. RESULTS The relative concentration of 122 and 36 lipids was altered in UC treatment-naïve patients and UC remission patients, respectively, compared with healthy controls. The highest number of significant variations was in the phosphatidylcholine (PC), ceramide (Cer), and sphingomyelin (SM) composition. Multivariate analysis revealed discrimination among the study groups based on the lipid profile. Furthermore, changes in phosphatidylethanolamine(38:3), Cer(d18:1/24:0), and Cer(d18:1/24:2) were most distinctive between the groups. CONCLUSION This study revealed a discriminant mucosal lipid composition pattern between treatment-naïve UC patients, deep remission UC patients, and healthy controls. We report several distinctive lipids, which might be involved in the inflammatory response in UC, and could reflect the disease state.
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Affiliation(s)
- Joseph Diab
- Natural Products and Medicinal Chemistry Research Group, Department of Pharmacy Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway
| | - Terkel Hansen
- Natural Products and Medicinal Chemistry Research Group, Department of Pharmacy Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway
| | - Rasmus Goll
- Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.,Department of Medical Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - Hans Stenlund
- Swedish Metabolomics Center, Swedish University of Agricultural Sciences, Umeå, Sweden
| | - Maria Ahnlund
- Swedish Metabolomics Center, Swedish University of Agricultural Sciences, Umeå, Sweden
| | - Einar Jensen
- Natural Products and Medicinal Chemistry Research Group, Department of Pharmacy Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway
| | - Thomas Moritz
- Department of Medical Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - Jon Florholmen
- Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.,Department of Medical Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - Guro Forsdahl
- Natural Products and Medicinal Chemistry Research Group, Department of Pharmacy Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway
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