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1
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Rogler G. [Efficient treatment of mild Crohn's disease and mild ulcerative colitis]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2025; 66:15-21. [PMID: 39715834 PMCID: PMC11761793 DOI: 10.1007/s00108-024-01840-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/12/2024] [Indexed: 12/25/2024]
Abstract
The cornerstone of treatment for mild ulcerative colitis is still the oral or topical (rectal) application of aminosalicylates (5-ASA). 5‑ASA preparations are often only administered orally in mild ulcerative colitis. Study data show that in ulcerative proctitis and left-sided colitis, rectal 5‑ASA preparations are even more effective than oral administration. In a next step, steroid-containing topical therapies should be used. Topical steroids such as budesonide are also primarily used in mild Crohn's disease. However, it is controversial whether treatment is necessary in symptom-free patients. There is still a lack of evidence to prove that more aggressive treatment (using immunosuppressants, biologics or small molecules) has a long-term benefit in these patients. Most guidelines are critical of the use of 5‑ASA in mild Crohn's disease. Nevertheless, there is some evidence for sufficiently high-dose treatment with 5‑ASA, although one must be aware of its limited effectiveness. However, there is clear evidence for the postoperative use of 5‑ASA in cases of mild recurrence.
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Affiliation(s)
- Gerhard Rogler
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Rämistrasse 100, 8091, Zürich, Schweiz.
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O'Donnell JEM, Walters TD, Benchimol EI. Advancements in the management of pediatric inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2024; 18:815-827. [PMID: 39688852 DOI: 10.1080/17474124.2024.2444555] [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: 08/24/2024] [Revised: 11/22/2024] [Accepted: 12/16/2024] [Indexed: 12/18/2024]
Abstract
INTRODUCTION The management of pediatric inflammatory bowel disease (PIBD) has drastically changed in the last decade. The limited availability of new biologics or small molecule therapies, and concerns about durability in children has necessitated the development of other advances in management to optimize care. AREAS COVERED This review covers guidance for management targets and advances in optimizing biologic therapies, new medical therapies, adjuvant therapies, precision medicine and mental health concerns in PIBD. This review focused on recent advances and was not intended as a complete overview of the investigations and management of pediatric IBD. EXPERT OPINION Advancements include standardization of treatment goals via a treat-to-target strategy, optimizing anti-TNF biologics through combination therapy or proactive drug monitoring, earlier initiation of treatment for Crohn's disease, the emergence of new biologic/advanced therapies and a growing focus on adjuvant therapies targeting the microbiome. Future progress relies on the inclusion of children/adolescents in clinical trials to facilitate faster regulatory approval for pediatric therapies and the integration of precision medicine and mental health screening to improve patient care and outcomes.
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Affiliation(s)
- Jonathan E M O'Donnell
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada
- Department of Paediatrics, University of Toronto, Toronto, Canada
| | - Thomas D Walters
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada
- Department of Paediatrics, University of Toronto, Toronto, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
| | - Eric I Benchimol
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada
- Department of Paediatrics, University of Toronto, Toronto, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Canada
- ICES, Toronto, Canada
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3
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Gros B, Blackwell J, Segal J, Black CJ, Ford AC, Din S. Harms with placebo in trials of biological therapies and small molecules as maintenance therapy in inflammatory bowel disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2024; 9:1030-1040. [PMID: 39307146 DOI: 10.1016/s2468-1253(24)00233-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 07/16/2024] [Accepted: 07/17/2024] [Indexed: 10/14/2024]
Abstract
BACKGROUND Randomised placebo-controlled trials for the induction of inflammatory bowel disease (IBD) remission involve potential harms to those receiving placebo. Whether these harms are also apparent with placebo during maintenance of remission trials in IBD is unclear. We aimed to examine the potential harms associated with receiving placebo in trials of licensed biologics and small molecules for maintenance of remission of ulcerative colitis and luminal Crohn's disease in a meta-analysis. METHODS We performed a systematic review and meta-analysis. We searched several medical literature databases including MEDLINE (from Jan 1, 1946, to May 31, 2024), Embase and Embase Classic (Jan 1, 1947, to May 31, 2024), and the Cochrane Central Register of Controlled Trials from database inception to May 31, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for maintenance of remission in adults with IBD reporting data on adverse events over a period of 20 weeks or more. There were no language restrictions or prespecified exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, drug-related adverse event, infection, worsening of IBD activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events, reporting relative risks (RRs) for placebo versus active drug with 95% CIs for each outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42024542624). FINDINGS Our search identified 10 826 citations, of which 45 trials including 16 562 patients (10 319 [62·3%] receiving active drug and 6243 [37·7%] placebo) were eligible. The risks of any treatment-emergent adverse event (7297/9546 [76·4%] patients on active drug vs 4415/5850 [75·5%] on placebo; RR 1·01, 95% CI 0·99-1·04; I2 =47%), serious infection (260/10 242 [2·5%] vs 155/6149 [2·5%]; 0·97, 0·79-1·19; I2 =0%), or venous thromboembolic event (12/4729 [0·3%] vs 9/2691 [0·3%]; 0·72, 0·31-1·66; I2 =0%) were not significantly lower with active drug than placebo. The risks of any infection (3208/8038 [39·9%] vs 1713/4809 [35·6%]; 1·14, 1·05-1·23; I2 =60%) or any drug-related adverse event (1094/2997 [36·5%] vs 609/1950 [31·2%]; 1·24, 1·02-1·50; I2 =75%) were higher with active drug than placebo. However, the risks of any worsening of IBD activity (1038/8090 [12·8%] vs 1181/5191 [22·8%]; 0·58, 0·52-0·64; I2 =40%), any withdrawal due to adverse events (610/10 282 [5·9%] vs 561/6207 [9·0%]; 0·71, 0·60-0·84; I2 =43%), any serious adverse events (1066/10 292 [10·4%] vs 742/6198 [12·0%]; 0·85, 0·77-0·94; I2 =17%), or any serious worsening of IBD activity (101/5707 [1·8%] vs 143/3640 [3·9%]; 0·55, 0·42-0·71; I2 =0%) were lower with active drug than placebo. 21 randomised controlled trials were judged as low risk of bias across all domains. INTERPRETATION In maintenance of remission trials in IBD, placebo was associated with some clinically significant potential harms. Patients should be counselled about these before participating in clinical trials and consideration given to alternative designs to test novel drugs in IBD. FUNDING None.
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Affiliation(s)
- Beatriz Gros
- Department of Gastroenterology, Reina Sofía University Hospital, Cordoba, Spain; Maimonides Biomedical Research Institute of Cordoba, University of Cordoba, Cordoba, Spain; Biomedical Research Center in Hepatic and Digestive Disease, CIBEREHD, Madrid, Spain
| | - Jonathan Blackwell
- Edinburgh Inflammatory Bowel Diseases Unit, Western General Hospital, Edinburgh, UK
| | - Jonathan Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia
| | - Christopher J Black
- Leeds Gastroenterology Institute, St James's University Hospital, University of Leeds, Leeds, UK; Leeds Institute of Medical Research, St James's University Hospital, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, University of Leeds, Leeds, UK; Leeds Institute of Medical Research, St James's University Hospital, University of Leeds, Leeds, UK
| | - Shahida Din
- Edinburgh Inflammatory Bowel Diseases Unit, Western General Hospital, Edinburgh, UK; Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, UK.
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Tursi A, D’Avino A, Brandimarte G, Mocci G, Pellegrino R, Savarino EV, Gravina AG, the HERICIUM-UC Study Group. Enhancing Oral 5-ASA Effectiveness in Mild-to-Moderate Ulcerative Colitis through an H. erinaceus-Based Nutraceutical Add-on Multi-Compound: The "HERICIUM-UC" Two-Arm Multicentre Retrospective Study. Pharmaceutics 2024; 16:1133. [PMID: 39339171 PMCID: PMC11434695 DOI: 10.3390/pharmaceutics16091133] [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: 06/25/2024] [Revised: 08/03/2024] [Accepted: 08/16/2024] [Indexed: 09/30/2024] Open
Abstract
Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T1) and 60.2% at six months (T2), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1) and 70.4% (T2), with clinical remission rates of 30.4% (T1) and 50.9% (T2). No significant differences in clinical response rates between the groups at T1 (p = 0.231) and T2 (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 (p = 0.005) and T2 (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC.
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Affiliation(s)
- Antonio Tursi
- Territorial Gastroenterology Service, Barletta-Andria-Trani Local Health Agency, Via Fornaci, 76123 Andria, Italy
- Department of Medical and Surgical Sciences, Catholic University of Rome, Largo A. Gemelli, 00168 Roma, Italy
| | - Alessandro D’Avino
- Department of Internal Medicine, IRCCS Istituto Dermopatico dell’Immacolata, 00167 Roma, Italy
| | | | - Giammarco Mocci
- SC Gastroenterologia, ARNAS Brotzu, Piazzale A. Ricchi, 09047 Cagliari, Italy
| | - Raffaele Pellegrino
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Napoli, Italy
| | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Via VIII Febbraio, 35121 Padova, Italy
| | - Antonietta Gerarda Gravina
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Napoli, Italy
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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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Pasternak B. Medical management of pediatric inflammatory bowel disease. Semin Pediatr Surg 2024; 33:151398. [PMID: 38582057 DOI: 10.1016/j.sempedsurg.2024.151398] [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] [Indexed: 04/08/2024]
Abstract
Management of inflammatory bowel disease, both Crohn's disease (CD) and ulcerative colitis (UC), has seen a seismic shift over the past decade. Over the past five years, there has been the introduction of many new therapies with differing mechanisms of action and a goal of achieving mucosal healing, as well as clinical and biochemical remission (1,2). In addition, management is aimed at restoring normal growth and normalizing quality of life. The ultimate goal is to individualize medical management and determine the right drug for the right patient by identifying which inflammatory pathway is predominant and avoiding unwarranted lack of efficacy or side effects through biomarkers and risk prognostication. Patient's age, location of disease, behavior (inflammatory vs. penetrating/structuring), severity and growth delay all play into deciding on the best treatment approach. Ultimately, early intervention is key in preventing complications. The therapeutic approaches to management can be broken down to nutritional therapy, biologic agents, immunomodulators (including corticosteroids), aminosalicylates and antibiotics. There are numerous other therapies, such as small molecule agents recently approved in adults, which are garnering a great deal of interest.
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Affiliation(s)
- Brad Pasternak
- Division of Pediatric Gastroenterology, Department of Pediatrics, Phoenix Children's Hospital, Phoenix, Arizona, USA.
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7
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Ota T, Takebe T, Shimizu Y, Orido T, Tanaka H, Nakamura S. Analysis of the Medication Persistence Rate for and Adherence to Oral 5-Aminosalicylic Acid Preparations in Japanese Patients with Ulcerative Colitis: Study Using a Nationwide Claims Database. Digestion 2024; 105:232-242. [PMID: 38527451 PMCID: PMC11152024 DOI: 10.1159/000538319] [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: 09/12/2023] [Accepted: 03/11/2024] [Indexed: 03/27/2024]
Abstract
INTRODUCTION 5-aminosalicylic acid (5-ASA) is the first-line drug for the treatment of mild-to-moderate ulcerative colitis (UC). Three oral sustained-release formulations are often used. However, no unified view of their actual use in routine medical practice has been presented to date. METHODS Using a health insurance claims database, we extracted patients with an initial diagnosis of mild-to-moderate UC during the period from December 1, 2017, to March 31, 2022. For the three types of oral 5-ASA formulation, we calculated and compared descriptive statistics of medication persistence rates (MPR), proportions of days covered (PDC), and adherence proportion (PDC ≥80%) in the extracted population. RESULTS An oral 5-ASA formulation was used in combination with a topical preparation (cohort 1) in 899 patients, and oral 5-ASA was used alone (cohort 2) in 1,829 patients. In cohort 1, MPR at days 151-180 with concomitant use of topical formulation was significantly higher for the Multi Matrix System™ (MMX) formulation (65.2%) compared with that for pH-dependent formulation (51.7%, p < 0.025), while MPR tended to be higher for MMX than for the time-dependent formulation (56.4%, not significant). During days 151-180 after starting the oral formulation, MPR for MMX (66.7% and 65.8%) was higher than for pH-dependent (55.9% and 55.3%) and time-dependent (57.6% and 55.9%) formulations in cohorts 1 + 2 and 2, respectively. In cohort 1, there was a significant difference between MMX (68.3%) and pH-dependent (57.1%) formulations, but no significant difference was seen with time-dependent formulations (61.8%). In terms of the proportion of adherence until day 180, MMX was significantly better than the other formulations. CONCLUSION The analyses of the three oral 5-ASA formulations suggested that both MPR and medication adherence were better for the MMX formulation than for time-dependent or pH-dependent formulations.
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Affiliation(s)
- Takumi Ota
- Medical Affairs Department, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Takahiro Takebe
- Medical Affairs Department, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Yutaka Shimizu
- Medical Affairs Department, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Takashi Orido
- Medical Affairs Department, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Hiroyuki Tanaka
- Medical Affairs Department, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Shiro Nakamura
- Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan
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Liu M, Gu L, Zhang Y, Zhou H, Wang Y, Xu ZX. A real-world disproportionality analysis of mesalazine data mining of the public version of FDA adverse event reporting system. Front Pharmacol 2024; 15:1290975. [PMID: 38357304 PMCID: PMC10864552 DOI: 10.3389/fphar.2024.1290975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 01/18/2024] [Indexed: 02/16/2024] Open
Abstract
Background: Mesalazine, a preparation of 5-aminosalicylic acid, is a medication widely used in clinical practice as a first-line therapy in the treatment of mild and moderate inflammatory bowel disease. However, the long-term safety of mesalazine in large sample population was unknown. The current study was to assess mesalazine -related adverse events of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio the Bayesian confidence propagation neural network and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of mesalazine -associated AEs. Results: Out of 14,149,980 reports collected from the FDA Adverse Event Reporting System database, 24,284 reports of mesalazine -associated AEs were identified. A total of 170 significant disproportionality preferred terms conforming to the four algorithms simultaneously were retained. The most common AEs included colitis ulcerative, diarrhoea, condition aggravated, crohn's disease, fatigue, abdominal pain, nausea, haematochezia, which were corresponding to those reported in the specification and clinical trials. Unexpected significant AEs as dizziness, drug ineffective, drug hypersensitivity, infection, off label use, weight decreased, decreased appetite, arthralgia, rash might also occur. The median onset time of mesalazine -related AEs was 1,127 days (interquartile range [IQR] 1,127-1,674 days), and most of the cases occurred 2 years later (n = 610, 70.93%) and within the first 1 month (n = 89, 10.35%) after mesalazine initiation. Conclusion: Results of our study were consistent with clinical observations. We also found potential new and unexpected AEs signals for mesalazine, suggesting prospective clinical studies were needed to confirm these results and illustrate their relationship. Our results could provide valuable evidence for further safety studies of mesalazine.
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Affiliation(s)
- Mingdi Liu
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
| | - Liting Gu
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
| | - Yuning Zhang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
| | - Honglan Zhou
- Department of Urology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yishu Wang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
| | - Zhi-Xiang Xu
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin, China
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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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Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis. Lancet 2023; 402:571-584. [PMID: 37573077 DOI: 10.1016/s0140-6736(23)00966-2] [Citation(s) in RCA: 476] [Impact Index Per Article: 238.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/03/2023] [Accepted: 05/08/2023] [Indexed: 08/14/2023]
Abstract
Ulcerative colitis is a lifelong inflammatory disease affecting the rectum and colon to a variable extent. In 2023, the prevalence of ulcerative colitis was estimated to be 5 million cases around the world, and the incidence is increasing worldwide. Ulcerative colitis is thought to occur in people with a genetic predisposition following environmental exposures; gut epithelial barrier defects, the microbiota, and a dysregulated immune response are strongly implicated. Patients usually present with bloody diarrhoea, and the diagnosis is based on a combination of clinical, biological, endoscopic, and histological findings. The aim of medical management is, first, to induce a rapid clinical response and normalise biomarkers and, second, to maintain clinical remission and reach endoscopic normalisation to prevent long-term disability. Treatments for inducing remission include 5-aminosalicylic acid drugs and corticosteroids. Maintenance treatments include 5-aminosalicylic acid drugs, thiopurines, biologics (eg, anti-cytokines and anti-integrins), and small molecules (Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators). Although the therapeutic options are expanding, 10-20% of patients still require proctocolectomy for medically refractory disease. The keys to breaking through this therapeutic ceiling might be the combination of therapeutics with precision and personalised medicine.
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Affiliation(s)
- Catherine Le Berre
- Institut des Maladies de l'Appareil Digestif, Hépato-Gastro-Entérologie et Assistance Nutritionnelle, Inserm CIC 1413, Inserm UMR 1235, Nantes Université, CHU Nantes, Nantes, France
| | - Sailish Honap
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK; School of Immunology and Microbial Sciences, King's College London, London UK
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, INFINY Institute, FHU-CURE, INSERM NGERE, Nancy University Hospital, Vandœuvre-lès-Nancy, France; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada.
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11
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Hey GE, Vedam-Mai V, Beke M, Amaris M, Ramirez-Zamora A. The Interface between Inflammatory Bowel Disease, Neuroinflammation, and Neurological Disorders. Semin Neurol 2023; 43:572-582. [PMID: 37562450 DOI: 10.1055/s-0043-1771467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Abstract
Inflammatory Bowel Disease (IBD) is a complex, chronic inflammatory condition affecting the gastrointestinal tract. IBD has been associated with a variety of neurologic manifestations including peripheral nerve involvement, increased risk of thrombotic, demyelinating and events. Furthermore, an evolving association between IBD and neurodegenerative disorders has been recognized, and early data suggests an increased risk of these disorders in patients diagnosed with IBD. The relationship between intestinal inflammatory disease and neuroinflammation is complex, but the bidirectional interaction between the brain-gut-microbiome axis is likely to play an important role in the pathogenesis of these disorders. Identification of common mechanisms and pathways will be key to developing potential therapies. In this review, we discuss the evolving interface between IBD and neurological conditions, with a focus on clinical, mechanistic, and potentially therapeutic implications.
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Affiliation(s)
- Grace E Hey
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
| | - Vinata Vedam-Mai
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
| | - Matthew Beke
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
- Department of Food Science and Human Nutrition, University of Florida, Gainesville, Florida
| | - Manuel Amaris
- Department of Gastroenterology, University of Florida, Gainesville, Florida
| | - Adolfo Ramirez-Zamora
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
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12
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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. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [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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13
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Shelygin YA, Ivashkin VT, Belousova EA, Reshetov IV, Maev IV, Achkasov SI, Abdulganieva DI, Alekseeva OA, Bakulin IG, Barysheva OY, Bolikhov KV, Vardanyan AV, Veselov AV, Veselov VV, Golovenko OV, Gubonina IV, Denisenko VL, Dolgushina AI, Kashnikov VN, Knyazev OV, Kostenko NV, Lakhin AV, Makarchuk PA, Moskalev AI, Nanaeva BA, Nikitin IG, Nikitina NV, Odintsova AK, Omelyanovskiy VV, Оshchepkov AV, Pavlenko VV, Poluektova EA, Sitkin SI, Sushkov OI, Tarasova LV, Tkachev AV, Тimerbulatov VM, Uspenskaya YB, Frolov SA, Khlynova OV, Chashkova EY, Chesnokova OV, Shapina MV, Sheptulin AA, Shifrin OS, Shkurko TV, Shchukina OB. Ulcerative colitis (K51), adults. KOLOPROKTOLOGIA 2023; 22:10-44. [DOI: 10.33878/2073-7556-2023-22-1-10-44] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Affiliation(s)
- Yu. A. Shelygin
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | - V. T. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - I. V. Reshetov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - I. V. Maev
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov
| | - S. I. Achkasov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | | | | | - I. G. Bakulin
- North-Western State Medical University named after I.I. Mechnikov
| | | | | | | | | | - V. V. Veselov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | - O. V. Golovenko
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | | | - V. L. Denisenko
- Educational Establishment Vitebsk State Order of Peoples’ Friendship Medical University
| | - A. I. Dolgushina
- Federal State Budgetary Educational Institution of Higher Education «South-Ural State Medical University» of the Ministry of Healthcare of the Russian Federation
| | | | - O. V. Knyazev
- GBUZ Moscow Clinical Scientific Center named after Loginov MHD
| | - N. V. Kostenko
- Federal State Budgetary Educational Institution of Higher Education «Astrakhan State Medical University» of the Ministry of Health of the Russian Federation
| | | | | | - A. I. Moskalev
- Ryzhikh National Medical Research Center of Coloproctology
| | - B. A. Nanaeva
- Ryzhikh National Medical Research Center of Coloproctology
| | - I. G. Nikitin
- Pirogov Russian National Research Medical University
| | | | - A. Kh. Odintsova
- GAUZ «RCH» of the Ministry of Health of the Republic of Tatarstan
| | | | - A. V. Оshchepkov
- GBUZ SO «SOKB No. 1» of the Ministry of Health of the Sverdlovsk Region
| | | | - E. A. Poluektova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - S. I. Sitkin
- North-Western State Medical University named after I.I. Mechnikov
| | - O. I. Sushkov
- Ryzhikh National Medical Research Center of Coloproctology
| | - L. V. Tarasova
- Federal State Budgetary Educational Institution of Higher Education «Chuvash State University named after I.N. Ulyanov»
| | - A. V. Tkachev
- Federal State Budgetary Educational Institution of Higher Education «Rostov State Medical University» of the Ministry of Health of the Russian Federation
| | | | | | - S. A. Frolov
- Ryzhikh National Medical Research Center of Coloproctology
| | - O. V. Khlynova
- Perm State Medical University named after E.A. Wagner (PSMU) of the Ministry of Healthcare of the Russian Feaderation
| | - E. Yu. Chashkova
- Federal State Budgetary Scientific Institution «Irkutsk Scientific Center for Surgery and Traumatology»
| | | | - M. V. Shapina
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | - A. A. Sheptulin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - O. S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - T. V. Shkurko
- Ryzhikh National Medical Research Center of Coloproctology
| | - O. B. Shchukina
- First St. Petersburg State Medical University named after Academician I.P. Pavlov of the Ministry of Health of Russia
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14
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Gonzalez M, Stephens M. 5-Aminosalicylate Therapy. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:339-347. [DOI: 10.1007/978-3-031-14744-9_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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15
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Liu Q, Jian W, Wang L, Yang S, Niu Y, Xie S, Hayer K, Chen K, Zhang Y, Guo Y, Tu Z. Alleviation of DSS-induced colitis in mice by a new-isolated Lactobacillus acidophilus C4. Front Microbiol 2023; 14:1137701. [PMID: 37152759 PMCID: PMC10157218 DOI: 10.3389/fmicb.2023.1137701] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 04/03/2023] [Indexed: 05/09/2023] Open
Abstract
Introduction Probiotic is adjuvant therapy for traditional drug treatment of ulcerative colitis (UC). In the present study, Lactobacillus acidophilus C4 with high acid and bile salt resistance has been isolated and screened, and the beneficial effect of L. acidophilus C4 on Dextran Sulfate Sodium (DSS)-induced colitis in mice has been evaluated. Our data showed that oral administration of L. acidophilus C4 remarkably alleviated colitis symptoms in mice and minimized colon tissue damage. Methods To elucidate the underlying mechanism, we have investigated the levels of inflammatory cytokines and intestinal tight junction (TJ) related proteins (occludin and ZO-1) in colon tissue, as well as the intestinal microbiota and short-chain fatty acids (SCFAs) in feces. Results Compared to the DSS group, the inflammatory cytokines IL-1β, IL-6, and TNF-α in L. acidophilus C4 group were reduced, while the antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were found to be elevated. In addition, proteins linked to TJ were elevated after L. acidophilus C4 intervention. Further study revealed that L. acidophilus C4 reversed the decrease in intestinal microbiota diversity caused by colitis and promoted the levels of SCFAs. Discussion This study demonstrate that L. acidophilus C4 effectively alleviated DSS-induced colitis in mice by repairing the mucosal barrier and maintaining the intestinal microecological balance. L. acidophilus C4 could be of great potential for colitis therapy.
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Affiliation(s)
- Qianqian Liu
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Wenwen Jian
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Lu Wang
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Shenglin Yang
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Yutian Niu
- International Medical College, Chongqing Medical University, Chongqing, China
| | - ShuaiJing Xie
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Kim Hayer
- Leicester Medical School, University of Leicester, Leicester, United Kingdom
| | - Kun Chen
- College of Foreign Languages, Chongqing Medical University, Chongqing, China
| | - Yi Zhang
- International Medical College, Chongqing Medical University, Chongqing, China
| | - Yanan Guo
- International Medical College, Chongqing Medical University, Chongqing, China
| | - Zeng Tu
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
- *Correspondence: Zeng Tu,
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16
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Lee WS, Arai K, Alex G, Treepongkaruna S, Kim KM, Choong CL, Mercado KS, Darma A, Srivastava A, Aw MM, Huang J, Ni YH, Malik R, Tanpowpong P, Tran HN, Ukarapol N. Medical Management of Pediatric Inflammatory Bowel Disease (PIBD) in the Asia Pacific Region: A Position Paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group. J Gastroenterol Hepatol 2022; 38:523-538. [PMID: 36574956 DOI: 10.1111/jgh.16097] [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: 07/23/2022] [Revised: 11/08/2022] [Accepted: 12/25/2022] [Indexed: 12/29/2022]
Abstract
Pediatric inflammatory bowel disease (PIBD) is rising rapidly in many industrialised and affluent areas in the Asia Pacific region. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in this region due to differences in disease characteristics and regional resources constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) with the aim of providing an up-to-date, evidence-based approach to PIBD in the Asia Pacific region, taking into consideration the unique disease characteristics and financial resources available in this region. A group of pediatric gastroenterologists with special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management and monitoring. Gastrointestinal infections, including tuberculosis, need to be excluded before diagnosing IBD. In some populations in Asia, the Nudix Hydrolase 15 (NUD15) gene is a better predictor of leukopenia induced by azathioprine than thiopurine-S-methyltransferase (TPMT). The main considerations in the use of biologics in the Asia Pacific region are high cost, ease of access, and potential infectious risk, especially tuberculosis. Conclusion: This position paper provides a useful guide to clinicians in the medical management of children with PIBD in the Asia Pacific region.
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Affiliation(s)
- Way Seah Lee
- Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Katsuhiro Arai
- Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, Tokyo, Japan
| | - George Alex
- Department of Gastroenterology and Nutrition, Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Suporn Treepongkaruna
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Chee Liang Choong
- Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Karen Sc Mercado
- Makati Medical Center and The Medical City, Philippine Society for Pediatric Gastroenterology, Hepatology and Nutrition, Manila, Philippines
| | - Andy Darma
- Department of Child Health, Dr. Soetomo General Hospital, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Anshu Srivastava
- Department of Paediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Marion M Aw
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - James Huang
- Division of Paediatric Gastroenterology, Nutrition, Hepatology and Liver Transplantation, Department of Paediatrics, National University Hospital, Singapore
| | - Yen Hsuan Ni
- National Taiwan University College of Medicine, Taiwan
| | - Rohan Malik
- Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Pornthep Tanpowpong
- Department of Pediatrics, Faculty of Medicine Ramathibodi, Mahidol University, Bangkok, Thailand
| | - Hong Ngoc Tran
- Department of Gastroenterology, Children's Hospital # 1, Ho Chi Minh City, Vietnam
| | - Nuthapong Ukarapol
- Department of Pediatric Gastroenterology and Hepatology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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17
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Aslam N, Lo SW, Sikafi R, Barnes T, Segal J, Smith PJ, Limdi JK. A review of the therapeutic management of ulcerative colitis. Therap Adv Gastroenterol 2022; 15:17562848221138160. [PMID: 36478780 PMCID: PMC9720837 DOI: 10.1177/17562848221138160] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 10/26/2022] [Indexed: 12/03/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic relapsing and remitting gastrointestinal disorder of uncertain aetiology. The last two decades have seen an expansion in the therapeutic arsenal used to treat UC. This has resulted in improved clinical remission and response rates. Nonetheless, staples in our current medical management originate from trials conducted in the early 20th century. In this review article, we aim to outline the key milestones in the history of the medical management of UC in addition to highlighting promising therapeutic developments for the future.
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Affiliation(s)
| | | | - Rafid Sikafi
- St Mark’s Hospital, London North West University Healthcare NHS Trust, London, UK
| | - Tom Barnes
- Section of IBD – Division of Gastroenterology, Northern Care Alliance NHS Foundation Trust, Salford, UK
| | - Jonathan Segal
- Northern Hospital, Epping, Melbourne, VIC, Australia,Department of Medicine, University of Melbourne, Parkville, VIC, Australia
| | - Philip J Smith
- Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals Foundation NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- Section of IBD – Division of Gastroenterology, Northern Care Alliance NHS Foundation Trust, Manchester, UK,Manchester Academic Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
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18
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Qiu B, Liang JX, Li C. Efficacy and safety of vedolizumab for inflammatory bowel diseases: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2022; 101:e30590. [PMID: 36221344 PMCID: PMC9543089 DOI: 10.1097/md.0000000000030590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Vedolizumab is a humanized monoclonal antibody that inhibits gut-selective α4β7 integrins on the surface of leukocytes, preventing their trafficking into the gastrointestinal tract, and ultimately achieves the effect of suppressing intestinal inflammation. This study aimed to evaluate the efficacy and safety of vedolizumab in the treatment of inflammatory bowel disease. METHODS After a systematic review of relevant studies, the pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated to evaluate the effect. Heterogeneity was explored using sensitivity analysis, univariate meta-regression, and subgroup analysis. Potential publication bias was evaluated using Egger test and trim-and-fill method. RESULTS Nine randomized controlled trials involving 4268 participants were included in the meta-analysis. During induction therapy, vedolizumab was more effective than placebo in treating active ulcerative colitis and Crohn disease in terms of clinical response (RR = 1.55, 95%CI: 1.35-1.78), clinical remission (RR = 1.90, 95%CI: 1.50-2.41), and mucosal healing (RR = 1.53, 95%CI: 1.21-1.95). A superior effect in terms of durable Clinical or Crohn disease Activity Index-100 response (RR = 1.65, 95%CI: 1.20-2.26), clinical remission (RR = 1.92, 95%CI: 1.48-2.50), and glucocorticoid-free remission (RR = 2.22, 95%CI: 1.71-2.90) was found during maintenance treatment. Vedolizumab was not associated with any adverse events and was as safe as placebo in terms of the risk of serious adverse reactions. CONCLUSIONS Vedolizumab may be safe and effective as an induction and maintenance therapy for the treatment of inflammatory bowel disease; however, further studies are needed to validate this conclusion.
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Affiliation(s)
- Bo Qiu
- International Doctoral School, University of Seville, Faculty of Medicine, Seville, Spain
| | - Jia-Xu Liang
- International Doctoral School, University of Seville, Faculty of Medicine, Seville, Spain
- Department of Diagnostic Radiology, The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People’s Hospital), Zhengzhou, China
| | - Cong Li
- Department of Endocrinology of North District, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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19
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Park J, Cheon JH. Updates on conventional therapies for inflammatory bowel diseases: 5-aminosalicylates, corticosteroids, immunomodulators, and anti-TNF-α. Korean J Intern Med 2022; 37:895-905. [PMID: 35882566 PMCID: PMC9449200 DOI: 10.3904/kjim.2022.132] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 05/13/2022] [Indexed: 12/03/2022] Open
Abstract
The incidence and prevalence of inflammatory bowel diseases (IBDs) are rapidly increasing worldwide. IBDs are considered an emerging problem not only in Western countries but also in developing counties. The relapses and complications of active IBD mandate various medications. Nevertheless, hospitalization, emergency room visits, or surgery may be required, resulting in a socioeconomic burden. Great advances have been made in the development of new therapeutic options for IBD to achieve induction and maintenance remission. Nevertheless, conventional therapy is still the mainstay in the treatment of IBD. This review article provides an update on recent advances in conventional therapies, including 5-aminosalicylates, corticosteroids, immunomodulators, and anti-tumor necrosis factor-α agents to treat IBD.
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Affiliation(s)
- Jihye Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
| | - Jae Hee Cheon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
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20
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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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21
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Cai C, Lu J, Lai L, Song D, Shen J, Tong J, Zheng Q, Wu K, Qian J, Ran Z. Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia. Intest Res 2022; 20:213-223. [PMID: 35508955 PMCID: PMC9081996 DOI: 10.5217/ir.2021.00031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 02/07/2022] [Indexed: 11/17/2022] Open
Abstract
Background/Aims The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. Methods A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. Results In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. Conclusions The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.
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22
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Saiki JP, Andreasson JO, Grimes KV, Frumkin LR, Sanjines E, Davidson MG, Park KT, Limketkai B. Treatment-refractory ulcerative colitis responsive to indigo naturalis. BMJ Open Gastroenterol 2022; 8:bmjgast-2021-000813. [PMID: 34969665 PMCID: PMC8718466 DOI: 10.1136/bmjgast-2021-000813] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
Background Indigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model. Methods This open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500 mg/day or 1.5 g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression. Results Ten of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN. Conclusion IN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation. Trial registration number NCT02442960.
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Affiliation(s)
- Julie P Saiki
- Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, USA
| | - Johan Ol Andreasson
- Department of Genetics, Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA
| | - Kevin V Grimes
- Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, USA
| | - Lyn R Frumkin
- Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, USA
| | - Elvi Sanjines
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | | | - K T Park
- Division of Pediatric Gastroenterology, Stanford University School of Medicine, Stanford, California, USA
| | - Berkeley Limketkai
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
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23
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Burr NE, Gracie DJ, Black CJ, Ford AC. Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis. Gut 2021; 71:gutjnl-2021-326390. [PMID: 34937767 DOI: 10.1136/gutjnl-2021-326390] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 12/02/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Biological therapies and small molecules continue to be evaluated in moderate to severely active ulcerative colitis, but are often studied in placebo-controlled trials, meaning their relative efficacy and safety is unknown. We examined this in a network meta-analysis. DESIGN We searched the literature to October 2021 to identify eligible trials. We judged efficacy using clinical remission, endoscopic improvement, or clinical response, and according to previous exposure or non-exposure to antitumour necrosis factor (TNF)-α therapy. We also assessed safety. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs. Interventions were ranked according to their P-score. RESULTS We identified 28 trials (12 504 patients). Based on failure to achieve clinical remission, upadacitinib 45 mg once daily ranked first versus placebo (RR 0.73; 95% CI 0.68 to 0.80, P-score 0.98), with infliximab 5 mg/kg and 10 mg/kg second and third, respectively. Upadacitinib ranked first for clinical remission in both patients naïve to anti-TNF-α drugs (RR 0.69; 95% CI 0.61 to 0.78, P-score 0.99) and previously exposed (RR 0.78; 95% CI 0.72 to 0.85, P-score 0.99). Upadacitinib was superior to almost all other drugs in these analyses. Based on failure to achieve endoscopic improvement infliximab 10 mg/kg ranked first (RR 0.61; 95% CI 0.51 to 0.72, P-score 0.97), with upadacitinib 45 mg once daily, second, and infliximab 5 mg/kg third. Upadacitinib was more likely to lead to adverse events, but serious adverse events were no more frequent, and withdrawals due to adverse events were significantly lower than with placebo. Infections were significantly more likely with tofacitinib than placebo (RR 1.41; 95% CI 1.03 to 1.91). CONCLUSION In a network meta-analysis, upadacitinib 45 mg once daily ranked first for clinical remission in all patients, patients naïve to anti-TNF-α drugs and patients previously exposed. Infliximab 10 mg/kg ranked first for endoscopic improvement. Most drugs were safe and well tolerated.
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Affiliation(s)
- Nicholas E Burr
- Department of Gastroenterology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - David J Gracie
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Christopher J Black
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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24
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Kim YS. Treatment of inflammatory bowel diseases: focusing on 5-aminosalicylates and immunomodulators. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2021. [DOI: 10.5124/jkma.2021.64.9.596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background: Recently, the incidence and prevalence rates of inflammatory bowel disease (IBD) have increased worldwide, including in Korea. Although there has been considerable progress in the management of IBD following the discovery of biologic agents, 5-aminosalicylate (5-ASA) and immunomodulators are still considered cornerstones in the management of mild to moderate IBD.Current Concepts: 5-ASA plays a key role in inducing remission in patients with mild to moderate ulcerative colitis. High doses of 5-ASA are more effective in inducing remission in patients with moderate ulcerative colitis, and combination therapy of oral 5-ASA and topical 5-ASA agents is recommended. Although the effect of 5-ASA in patients with Crohn disease is limited, high doses of 5-ASA can be effective for patients with mild disease, inflammatory behavior, and colonic involvement. Maintaining remission is essential for patients with IBD. Good doctor-patient relationships and encouraging drug adherence are recommended. Regarding drug adherence, a once-daily regimen is preferred for patients’ satisfaction. Thiopurines, the most important immunomodulators, show therapeutic benefits, such as steroid-sparing effects and remission maintenance in ulcerative colitis and Crohn disease after induction therapy. However, several side effects, including severe leukopenia, can induce the discontinuation of thiopurines. Close monitoring and management decisions should be individualized according to the risk of relapse and adverse events.Discussion and Conclusion: In conclusion, 5-ASA and immunomodulators are cornerstones in the management of IBD. As such, clinicians should have knowledge of these drugs and patients’ characteristics for proper prescription.
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25
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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: 28] [Impact Index Per Article: 7.0] [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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26
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Gu FL, Huang RS, He XM, Chen NF, Han BX, Deng H. Dendrobium huoshanense Polysaccharides Prevent Inflammatory Response of Ulcerative Colitis Rat through Inhibiting the NF-κB Signaling Pathway. Chem Biodivers 2021; 18:e2100130. [PMID: 34080308 DOI: 10.1002/cbdv.202100130] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 05/25/2021] [Indexed: 12/12/2022]
Abstract
The polysaccharides of the Chinese herbal medicine Dendrobium huoshanense exhibit anti-inflammatory effects in multiple organs through regulating the immune responses. In the present study, we constructed ulcerative colitis (UC) model rats using dextran sulfate sodium to investigate the anti-inflammatory effects of D. huoshanense polysaccharides (DHP). After oral administration of DHP for two weeks, the indices of UC symptoms, including the ratio of colon weight to length, Disease Activity Index (DAI), and Colon Mucosal Damage Index (CMDI), all decreased significantly compared with the UC model group. The histological sections also revealed better cell orders in DHP treatments than in the UC model rats. Moreover, in treatment with high dose of DHP (200 mg/kg), the treatment efficacy arrived the similar levels to those in the treatment with 300 mg/kg sulfasalazine, which is a typical medicine to treat UC. These results indicated that DHP has a high efficacy to treat UC in model rats. Furthermore, serum levels of interleukin-1β, tumor necrosis factor-α, interleukin-17, and transforming growth factor-β were assessed using the enzyme linked immunosorbent assay (ELISA) method, and the levels of nuclear factor-κB in colon tissue sections were determined using the immunohistochemical method. The results showed that all these indices decreased significantly after administration of DHP in UC model rats, which might be the mechanisms underlying the DHP-suppressed UC inflammation. Overall, this study indicated that DHP might be directly used to treat UC and is a promising source to develop novel drugs against UC.
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Affiliation(s)
- Fang-Li Gu
- College of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, 237012, P. R. China.,Anhui Province Traditional Chinese Medicine Resource Protection and Sustainable Utilization Engineering Laboratory, Lu'an, 237012, P. R. China
| | - Ren-Shu Huang
- College of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, 237012, P. R. China.,Anhui Province Traditional Chinese Medicine Resource Protection and Sustainable Utilization Engineering Laboratory, Lu'an, 237012, P. R. China
| | - Xiao-Mei He
- College of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, 237012, P. R. China.,Anhui Province Traditional Chinese Medicine Resource Protection and Sustainable Utilization Engineering Laboratory, Lu'an, 237012, P. R. China
| | - Nai-Fu Chen
- College of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, 237012, P. R. China.,Anhui Province Traditional Chinese Medicine Resource Protection and Sustainable Utilization Engineering Laboratory, Lu'an, 237012, P. R. China
| | - Bang-Xing Han
- College of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, 237012, P. R. China.,Anhui Province Traditional Chinese Medicine Resource Protection and Sustainable Utilization Engineering Laboratory, Lu'an, 237012, P. R. China
| | - Hui Deng
- College of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, 237012, P. R. China.,Anhui Province Traditional Chinese Medicine Resource Protection and Sustainable Utilization Engineering Laboratory, Lu'an, 237012, P. R. China
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27
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Jin QW, Wang XD. Progress in research of vedolizumab in treatment of inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2021; 29:248-255. [DOI: 10.11569/wcjd.v29.i5.248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease is a kind of chronic inflammatory disease of the gastrointestinal tract with unclear etiology. At present, its main therapeutic drugs include aminosalicylates, glucocorticoids, immunosuppressive agents, and biological agents. With the deepening study of the disease and the progress of science and technology, there have been more and more studies on the targets for biological agents, including tumor necrosis factor-α, Janus kinase, interleukin, intestinal integrin, etc. As a humanized integrin antagonist, vedolizumab can selectively inhibit the interaction between integrin α4β7 and mucosal addressin cell adhesion molecule-1, and block the migration of lymphocytes to the intestinal tract to alleviate the intestinal inflammation, so as to achieve the therapeutic effect. This article reviews the mechanism, clinical efficacy, and application of vedolizumab in the treatment of inflammatory bowel disease.
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Affiliation(s)
- Qi-Wen Jin
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Xiao-Di Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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28
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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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29
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Dal Buono A, Roda G, Argollo M, Paridaens K, Peyrin-Biroulet L, Danese S. 'Treat to Target' in Mild to Moderate Ulcerative Colitis: Evidence to Support this Strategy. Curr Drug Targets 2020; 22:117-125. [PMID: 32718289 DOI: 10.2174/1389450121666200727120305] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 05/27/2020] [Accepted: 06/12/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND The management of chronic conditions, above all rheumatic disease and diabetes, now incorporates a "treat to target" strategy where treatment aims to achieve objective outcomes. This is applicable in ulcerative colitis (UC) as well. Targets are demonstrated to prevent endorgan dysfunction, specifically bowel damage and its complications, and lastly colorectal cancer. Recently, the scientific community has tried to define further targets beyond those currently recommended, namely mucosal healing and clinical remission. Studies that prospectively investigated this approach in UC are scanty and a treat-to-target (T2T) algorithm is not routinely used in daily clinical practice. OBJECTIVE We aim to review current evidence on T2T in UC and discuss its adoption in routine clinical practice as well as in clinical trials. METHODS A PubMed search was conducted in February 2020 to identify published papers investigating targets' achievement rates in UC. RESULTS Different targets can be achieved through approved drugs for mild to moderate UC; histological remission is emerging as a robust target with respect to long-term outcomes. CONCLUSION Further studies to compare a T2T strategy with the traditional care are needed, particularly in the mild to moderate spectrum of disease.
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Affiliation(s)
- Arianna Dal Buono
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
| | - Giulia Roda
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
| | - Marjorie Argollo
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University of Lorraine, 54500 Vandoeuvre-les- Nancy, France
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
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Ng SC, Mak JWY, Pal P, Banerjee R. Optimising management strategies of inflammatory bowel disease in resource-limited settings in Asia. Lancet Gastroenterol Hepatol 2020; 5:1089-1100. [PMID: 33181088 DOI: 10.1016/s2468-1253(20)30298-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 05/16/2020] [Accepted: 05/20/2020] [Indexed: 12/16/2022]
Abstract
Over the 21st century, inflammatory bowel disease (IBD) has become a global disease with increasing prevalence reported in the Asian subcontinent as a result of rapid urbanisation, industrialisation, and westernisation of lifestyles. Although rates of surgery have shown a temporal decrease globally because of the increasing availability of new drugs and early initiation of effective therapy, health-care costs associated with IBD have continued to rise. The increase in IBD prevalence in resource-limited countries poses a substantial health-care burden. Drugs are not universally accessible or available. An optimised and practical management strategy of IBD in resource-limited countries in Asia is urgently needed. Special consideration should be made to balance the risk of undertreatment (and suboptimal disease control) because of financial constraints with the risk of overtreatment, which is associated with side-effects and costly therapeutics. In this Series paper, we summarise the current approach in optimising conventional therapies, use of other therapies, and de-escalation of biologics in low-resource settings in Asia. The long-term objective is to strive for more effective and affordable therapies with sustained durability of benefit.
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Affiliation(s)
- Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
| | - Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Partha Pal
- IBD Centre, Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Rupa Banerjee
- IBD Centre, Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
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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. [Not Available]. 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] [MESH Headings] [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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Alkhatry M, Al-Rifai A, Annese V, Georgopoulos F, Jazzar AN, Khassouan AM, Koutoubi Z, Nathwani R, Taha MS, Limdi JK. First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus. World J Gastroenterol 2020; 26:6710-6769. [PMID: 33268959 PMCID: PMC7684461 DOI: 10.3748/wjg.v26.i43.6710] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 07/15/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis and Crohn's disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.
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Affiliation(s)
- Maryam Alkhatry
- Gastroenterology and Endoscopy Department, Ibrahim Bin Hamad Obaid Allah Hospital, Ministry of Health and Prevention, Ras Al Khaiman, United Arab Emirates
| | - Ahmad Al-Rifai
- Department of Gastroenterology, Sheikh Shakbout Medical City, Abu Dhabi, United Arab Emirates
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic, Dubai, United Arab Emirates
- Department of Gastroenterology and Endoscopy, American Hospital, Dubai, United Arab Emirates
| | | | - Ahmad N Jazzar
- Gastroenterology Division, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Ahmed M Khassouan
- Digestive Disease Unit, Rashid Hospital, Dubai, United Arab Emirates
| | - Zaher Koutoubi
- Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates
| | - Rahul Nathwani
- Department of Gastroenterology, Mediclinic City Hospital, Dubai, United Arab Emirates
- Department of Gastroenterology, Mohammed Bin Rashid University, Dubai, United Arab Emirates
| | - Mazen S Taha
- Gastroenterology and Hepatology, Tawam Hospital, Al Ain, United Arab Emirates
| | - Jimmy K Limdi
- Department of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester Academic Health Sciences, University of Manchester, Manchester M8 5RB, United Kingdom
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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: 86] [Impact Index Per Article: 17.2] [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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Abstract
Although management of inflammatory bowel disease follows a similar approach for all adults, there are certain characteristics making its treatment more challenging in older patients. The advent of novel medical treatments has changed the paradigm of inflammatory bowel disease, with an increasing focus on preventing disease progression in addition to controlling symptoms. The safety of these therapies in the elderly needs to be considered. Management of inflammatory bowel disease in the elderly is confounded by comorbidities that can increase the risk of medication or surgical complications; polypharmacy and altered pharmacokinetics also increase the risk of drug-drug interactions and adverse events.
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Affiliation(s)
- Shirley Cohen-Mekelburg
- Inflammatory Bowel Disease Program, VA Ann Arbor Healthcare System, VA Center for Clinical Management Research, 2215 Fuller Road, Ann Arbor, MI 48105, USA; Division of Gastroenterology & Hepatology, Department of Internal Medicine, Michigan Medicine, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA; Institute for Healthcare Policy and Innovation, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
| | - Akbar K Waljee
- Inflammatory Bowel Disease Program, VA Ann Arbor Healthcare System, VA Center for Clinical Management Research, 2215 Fuller Road, Ann Arbor, MI 48105, USA; Division of Gastroenterology & Hepatology, Department of Internal Medicine, Michigan Medicine, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA; Institute for Healthcare Policy and Innovation, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Michigan Integrated Center for Health Analytics and Medical Prediction (MiCHAMP), University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA. https://twitter.com/AkbarWaljee
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35
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Dhillon P, Singh K. Therapeutic applications of probiotics in ulcerative colitis: An updated review. PHARMANUTRITION 2020. [DOI: 10.1016/j.phanu.2020.100194] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Aniwan S, Limsrivilai J, Pongprasobchai S, Pausawasdi N, Prueksapanich P, Kongtub N, Rerknimitr R. Temporal trend in the natural history of ulcerative colitis in a country with a low incidence of ulcerative colitis from 2000 through 2018. Intest Res 2020; 19:186-193. [PMID: 32806871 PMCID: PMC8100373 DOI: 10.5217/ir.2020.00028] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 05/23/2020] [Indexed: 12/30/2022] Open
Abstract
Background/Aims The incidence of ulcerative colitis (UC) in Thailand (crude incidence rate of 0.28 per 100,000 persons) is much lower than in the West. The burden of UC varies in different populations. The aim of this study was to evaluate the natural history of UC over the two decades in Bangkok, Thailand. Methods This retrospective study included patients who were diagnosed with UC between 2000 and 2018 in 2 university hospitals. To evaluate changes in the disease course, we stratified patients into 2000–2009 cohort and 2010–2018 cohort. The cumulative probability of endoscopic healing, UC-related hospitalization and colectomy was estimated using the Kaplan-Meier method. Results A total of 291 UC patients were followed for total of 2,228 person-years. Comparison between 2 cohorts, there were no differences in disease pattern and severity whereas an increase in the combination use of oral and topical mesalamine and the early use of thiopurine was observed. Only 1% of patients for each cohort required biologic agent at 5 years. The rate of achieving mucosal healing increased from 15% to 46% at 3 years (P<0.01). The rate of UC-related hospitalization decreased from 30% to 21% at 5 years (P<0.05). The rate of colectomy decreased from 6% to 2% at 5 years (P<0.05). Conclusions The natural history of UC in a low incidence country was less aggressive than the West. Over the past two decades, the rates of UC-related hospitalization and colectomy have been decreasing which were similar to the West.
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Affiliation(s)
- Satimai Aniwan
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand
| | - Supot Pongprasobchai
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand
| | - Nonthalee Pausawasdi
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand
| | - Piyapan Prueksapanich
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Natanong Kongtub
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
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Sood A, Ahuja V, Midha V, Sinha SK, Pai CG, Kedia S, Mehta V, Bopanna S, Abraham P, Banerjee R, Bhatia S, Chakravartty K, Dadhich S, Desai D, Dwivedi M, Goswami B, Kaur K, Khosla R, Kumar A, Mahajan R, Misra SP, Peddi K, Singh SP, Singh A. Colitis and Crohn's Foundation (India) consensus statements on use of 5-aminosalicylic acid in inflammatory bowel disease. Intest Res 2020; 18:355-378. [PMID: 32646198 PMCID: PMC7609395 DOI: 10.5217/ir.2019.09176] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 04/04/2020] [Indexed: 12/16/2022] Open
Abstract
Despite several recent advances in therapy in inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) therapy has retained its place especially in ulcerative colitis. This consensus on 5-ASA is obtained through a modified Delphi process, and includes guiding statements and recommendations based on literature evidence (randomized trials, and observational studies), clinical practice, and expert opinion on use of 5-ASA in IBD by Indian gastroenterologists. The aim is to aid practitioners in selecting appropriate treatment strategies and facilitate optimal use of 5-ASA in patients with IBD.
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Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Saroj Kant Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - C Ganesh Pai
- Department of Gastroenterology, Kasturba Medical College, Manipal, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | | | - Philip Abraham
- P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Shobna Bhatia
- Department of Gastroenterology, King Edward Memorial Hospital, Mumbai, India
| | | | - Sunil Dadhich
- Department of Gastroenterology, Dr. Sampurnanand Medical College, Jodhpur, India
| | - Devendra Desai
- P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Manisha Dwivedi
- Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad, India
| | - Bhabhadev Goswami
- Department of Gastroenterology, Gauhati Medical College, Guwahati, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Rajeev Khosla
- Max Super Speciality Hospital, Saket, New Delhi, India
| | - Ajay Kumar
- BLK Super Speciality Hospital, New Delhi, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - S P Misra
- Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad, India
| | - Kiran Peddi
- Citizens Centre for Digestive Disorders, Hyderabad, India
| | - Shivaram Prasad Singh
- Department of Gastroenterology, Sriram Chandra Bhanj Medical College and Hospital, Cuttack, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
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Abstract
PURPOSE OF REVIEW Multiple new medications with novel mechanisms of action are now available to treat inflammatory bowel disease (IBD). Identifying the appropriate patients in whom to use these therapies is critical in maximizing benefit and reducing unnecessary risks. Once the appropriate therapy is selected, using a treat-to-target algorithm including symptomatic, biochemical, and endoscopic monitoring can improve clinical outcomes. If symptoms recur, these same principles, coupled with therapeutic drug monitoring, should be considered to confirm inflammation and determine next therapeutic steps. RECENT FINDINGS Multiple network meta-analyses can assist clinicians in determining the ideal biologic or small molecule therapy for patients with moderate-to-severe IBD. Once selected, several clinical trials have demonstrated that follow-up in 3 to 4 months, coupled with fecal calprotectin or C-reactive protein monitoring, can improve clinical remission and mucosal healing rates. Structural assessment should be performed via colonoscopy, enterography, or capsule endoscopy, dependent on disease location, at 9--12 months to confirm healing. SUMMARY Appropriate disease stratification, coupled with biologic or small molecule medication selection and treat-to-target follow-up, can greatly assist clinicians who are managing patients with IBD in achieving the greatest potential benefits of medical therapy.
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Positioning Therapies in Ulcerative Colitis. Clin Gastroenterol Hepatol 2020; 18:1280-1290.e1. [PMID: 31982609 DOI: 10.1016/j.cgh.2020.01.017] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 12/30/2019] [Accepted: 01/11/2020] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease (IBD) that affects the large intestine. Several therapeutic drug classes are available for the treatment of UC: salicylates, corticosteroids, thiopurines, calcineurin inhibitors, anti-tumor necrosis factor (TNF) agents, anti-adhesion molecules, and, more recently, small molecules directed against the Janus kinase (JAK) pathways, and ustekinumab (anti IL12/23). Other drugs are currently in development, and they will be probably available for UC patients in the near future. Several therapeutic algorithms have been proposed for the treatment of UC patients, yet these are predominantly based on expert opinions rather than high-quality evidence, mainly due to the lack of head-to-head trials, especially for monoclonal antibody and small molecule therapies. The optimal position of therapies in these algorithms remains unclear. Therefore, we conducted this review of the literature to provide an up-to-date overview of the available evidence on this topic.
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Pugliese N, Roda G, Peyrin-Biroulet L, Danese S. Emerging therapies for the treatment of ulcerative colitis. Expert Opin Emerg Drugs 2020; 25:1-9. [PMID: 32148112 DOI: 10.1080/14728214.2020.1737009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 02/27/2020] [Indexed: 12/16/2022]
Abstract
Introduction: Ulcerative colitis (UC) is a chronic idiopathic autoimmune inflammatory disorder, primarily affecting the gastrointestinal system. There are many patients affected that do not respond well to therapy and many others to which there is a loss of efficacy every year. The proportion of patients who have already experienced anti-TNF therapy is constantly increasing, making the development of new drugs with alternative mechanisms of action an important need for the treatment of UC.Areas covered: This review aims on emerging drugs in the treatment of UC and reviews data on their efficacy and safety.Expert opinion: UC, for many years, comparatively to CD, received little attention for several possible reasons, especially because it was not considered as a progressive disease able to induce irreversible bowel damage. This has led to lower investments by the scientific community and a slower development of therapeutic options for UC. In the past few years, this trend has started to change. In fact, new promising drugs have been developed and others are emerging with positive results. Although many treatment modalities have recently been approved, additional drugs are currently being investigated and will probably be part of the UC treatment regimen in the coming years.
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Affiliation(s)
- Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Giulia Roda
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
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Lu PD, Zhao YH. Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines. Chin Med 2020; 15:15. [PMID: 32063999 PMCID: PMC7011253 DOI: 10.1186/s13020-020-0296-z] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 01/30/2020] [Indexed: 12/15/2022] Open
Abstract
Nuclear factor-kappa B (NF-κB) is a kind of multi-functional nuclear transcription factor involved in regulating gene transcription to influence pathological evolution of inflammatory and immune diseases. Numerous literature evidence that NF-κB pathway plays an essential role in pathogenic development of ulcerative colitis (UC). UC is a chronic non-specific inflammatory bowel disease, and until now, therapeutic agents for UC including aminosalicylates, corticosteroids and immune inhibitors still cannot exert satisfied effects on patients. In recent years, Chinese medicines suggest the advantages of alleviating symptoms and signs, decreasing side-effects and recurrence, whose one of mechanisms is related to regulation of NF-κB pathway. In this review, we categorize Chinese medicines according to their traditional therapeutic functions, and summarize the characteristics of Chinese medicines targeting NF-κB pathway in UC treatment. It indicates that 85 kinds of Chinese medicines’ compounds and formulae can directly act on NF-κBp65; while 58 Chinese medicines’ ingredients and formulae indirectly suppress NF-κBp65 by regulation of its upstream or other related pathways. Moreover, by the analysis of Chinese medicines’ category based on their traditional functions, we conclude the category of dampness-drying and detoxificating medicine targeting NF-κB pathway accounts for primary status for amelioration of UC. Simultaneously, this review also contributes to the choices of Chinese medicine category and provides curative potential of Chinese medicines for clinical UC treatment.
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Affiliation(s)
- Peng-De Lu
- 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yong-Hua Zhao
- 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078 Macao, Special Administrative Region of China
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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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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: 1502] [Impact Index Per Article: 250.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 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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Fan Y, Yi W, Huang H, Mei Z, Feng Z. Efficacy of herbal medicine (Gegen Qinlian Decoction) on ulcerative colitis: A systematic review of randomized controlled trials. Medicine (Baltimore) 2019; 98:e18512. [PMID: 31876740 PMCID: PMC6946546 DOI: 10.1097/md.0000000000018512] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND This systematic review aims to evaluate the efficacy of Gegen Qinlian Decoction (GQD) for ulcerative colitis (UC). METHODS PubMed, EMBASE, Springer LINK, Cochrane Library, the China National Knowledge Infrastructure, Chongqing Weipu Database for Chinese Technical Periodicals, Wan-fang Database, and Chinese Biomedicine Database were searched from their inception to December 2018 for randomized controlled trials comparing the use of GQD alone or in combination with western medicine (WM) with that of WM therapies for UC. Outcomes on the therapy's effectiveness rate, ulcerative colitis endoscopic index of severity (UCEIS), recurrence rate, and adverse events were extracted and analyzed by Review Manager 5.3 software. Meta-analysis was combined with fixed or random-effects model, and risk ratios (RR) and 95% confidence intervals (CI) were calculated for all outcomes. Two researchers independently reviewed each trial to determine its inclusion. The Cochrane risk of bias assessment tool was used for quality assessment. RESULTS We included 22 trials involving 2028 patients with UC. When compared with WM therapy, GQD significantly improved the clinical effectiveness (n = 591, RR = 1.21, 95% CI: 1.12-1.31, P < .00001) and recurrence rate (n = 94, RR = 0.23, 95% CI: 0.10-0.54, P = .0006). GQD plus WM was more effective in improving the clinical effectiveness (n = 1337, RR = 1.21, 95% CI: 1.16-1.27, P < .00001), and decreasing UCEIS scores (n = 384, mean difference = -0.63, 95% CI: -1.26--0.01, P = .05), recurrence rate (n = 179, RR = 0.18, 95% CI: 0.06-0.61, P = .006). In addition, the adverse events for GQD (n = 238, RR = 0.20, 95% CI: 0.02-1.68, P = .14) and GQD plus WM (n = 427, RR = 0.37, 95% CI: 0.15-0.90, P = .03) was significantly lower than that for WM alone. Noted adverse events primarily included gastrointestinal symptoms, headache, dizziness, and leukocytopenia. CONCLUSIONS This meta-analysis shows that GQD used alone or in combination with WM might have potential benefits in curing UC. However, there is no sufficient evidence to draw definite conclusion supporting the effect of GQD for UC due to poor methodological quality of the included trials. More rigorously designed investigations and studies with large sample sizes should be conducted to establish clinical evidence further.
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Affiliation(s)
- Yuling Fan
- Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University
- Department of Traditional Chinese Medicine, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China
| | - Wen Yi
- Department of Traditional Chinese Medicine, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China
| | - Han Huang
- Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University
- Department of Traditional Chinese Medicine, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China
| | - Zhigang Mei
- Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University
| | - Zhitao Feng
- Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University
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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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46
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Törüner M, Akpınar H, Akyüz F, Dağlı Ü, Hamzaoğlu HÖ, Tezel A, Ünsal B, Yıldırım S, Çelik AF. 2019 Expert opinion on biological treatment use in inflammatory bowel disease management. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2019; 30:S913-S946. [PMID: 32207688 PMCID: PMC7372973 DOI: 10.5152/tjg.2019.061119] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 10/24/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Murat Törüner
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Hale Akpınar
- Department of Gastroenterology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Filiz Akyüz
- Department of Gastroenterology, İstanbul University School of Medicine, İstanbul, Turkey
| | - Ülkü Dağlı
- Department of Gastroenterology, Başkent University School of Medicine, İstanbul, Turkey
| | - Hülya Över Hamzaoğlu
- Department of Gastroenterology, İstanbul Acıbadem Fulya Hospital, İstanbul, Turkey
| | - Ahmet Tezel
- Department of Gastroenterology, Trakya University School of Medicine, Edirne, Turkey
| | - Belkıs Ünsal
- Department of Gastroenterology, Katip Çelebi University School of Medicine, İzmir, Turkey
| | - Süleyman Yıldırım
- Department of Gastroenterology, İstanbul University-Cerrahpaşa Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Aykut Ferhat Çelik
- Department of Gastroenterology, İstanbul University-Cerrahpaşa Cerrahpaşa School of Medicine, İstanbul, Turkey
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Xu L, Zhang Y, Xue X, Liu J, Li ZS, Yang GY, Song Y, Pan Y, Ma Y, Hu S, Wen A, Jia Y, Rodriguez LM, Tull MB, Benante K, Khan SA, Cao Y, Jovanovic B, Richmond E, Umar A, Bergan R, Wu K. A Phase I Trial of Berberine in Chinese with Ulcerative Colitis. Cancer Prev Res (Phila) 2019; 13:117-126. [PMID: 31619442 DOI: 10.1158/1940-6207.capr-19-0258] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/10/2019] [Accepted: 10/07/2019] [Indexed: 11/16/2022]
Abstract
The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.
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Affiliation(s)
- Li Xu
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yujie Zhang
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xianmin Xue
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jie Liu
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zeng-Shan Li
- Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University, Chicago, Illinois
| | - Ying Song
- Department of Pharmacology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yan Pan
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yueyun Ma
- Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Sijun Hu
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Aidong Wen
- Department of Pharmacology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yanyan Jia
- Department of Pharmacology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Luz Maria Rodriguez
- Division of Cancer Prevention, NCI, Bethesda, Maryland.,Walter Reed Military Medical Center, Department of Surgery, Bethesda, Maryland
| | - Mary Beth Tull
- Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois
| | - Kelly Benante
- Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois
| | - Seema A Khan
- Department of Surgery and Northwestern University, Chicago, Illinois
| | - Ying Cao
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Borko Jovanovic
- Department of Preventive Medicine, Northwestern University, Chicago, Illinois
| | | | - Asad Umar
- Division of Cancer Prevention, NCI, Bethesda, Maryland
| | - Raymond Bergan
- Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
| | - Kaichun Wu
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
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Nunes R, Neves JD, Sarmento B. Nanoparticles for the regulation of intestinal inflammation: opportunities and challenges. Nanomedicine (Lond) 2019; 14:2631-2644. [PMID: 31612773 DOI: 10.2217/nnm-2019-0191] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Prevalence of chronic inflammation of the gastrointestinal tract is increasing, emerging as a public health challenge. Conventional drug delivery systems targeting the colon have improved the treatment of inflammatory bowel disease. However, therapy frequently results in inconsistent efficacy and toxicity problems. Novel approaches based on nanoparticles offer several advantages over conventional dosage forms due to their ability to selectively target inflamed tissues. Several formulation efforts have been made in order to obtain increasingly selective nanosized systems, some with promising results in animal models of colitis. Despite all advances, no nanomedicines are yet approved for clinical use in inflammatory bowel disease. This review discusses the most recent efforts made toward the development of nanoparticles for regulating chronic intestinal inflammation.
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Affiliation(s)
- Rute Nunes
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.,INEB - Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal
| | - José das Neves
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.,INEB - Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal.,CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, 4585-116 Gandra, Portugal
| | - Bruno Sarmento
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.,INEB - Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal.,CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, 4585-116 Gandra, Portugal
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Sood A, Mahajan R, Singh A, Midha V, Mehta V, Narang V, Singh T, Singh Pannu A. Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients With Ulcerative Colitis: A Pilot Study. J Crohns Colitis 2019; 13:1311-1317. [PMID: 30873549 DOI: 10.1093/ecco-jcc/jjz060] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To study the role of faecal microbiota transplantation [FMT] in maintenance of remission in ulcerative colitis [UC]. METHODS In this pilot study, patients with UC in clinical remission achieved after multi-session FMT were randomly allocated to either maintenance FMT or placebo colonoscopic infusion every 8 weeks, for 48 weeks. The standard of care [SOC] therapy was continued in all patients. The primary endpoint was maintenance of steroid-free clinical remission [Mayo score ≤2, all subscores ≤1] at Week 48. Secondary endpoints were achievement of endoscopic remission [endoscopic Mayo score 0] and histological remission [Nancy grade 0, 1] at Week 48. RESULTS In all, 61 patients in clinical remission were randomised to receive either FMT [n = 31] or placebo [n = 30]. The primary outcome was achieved in 27/31 [87.1%] patients allocated FMT versus 20/30 [66.7%] patients assigned placebo [p = 0.111]. Secondary endpoints of endoscopic remission (FMT: 18/31 [58.1%] versus placebo: 8/30 [26.7%], p = 0.026) and histological remission (FMT: 14/31 [45.2%] versus placebo: 5/30 [16.7%], p = 0. 033) were achieved in a significantly higher number of patients with FMT. Three patients receiving FMT [9.7%] and 8 patients on placebo [26.7%] relapsed. There were no serious adverse events necessitating discontinuation in patients on FMT; one patient who relapsed on placebo required colectomy. CONCLUSIONS Maintenance FMT in patients who are in clinical remission may help sustain clinical, endoscopic and histological remission in patients with UC.
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Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, Punjab, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, Punjab, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, Punjab, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College & Hospital, Ludhiana, India
| | - Varun Mehta
- Department of Internal Medicine, Dayanand Medical College & Hospital, Ludhiana, India
| | - Vikram Narang
- Department of Pathology, Dayanand Medical College & Hospital, Ludhiana, Punjab, India
| | - Tarundeep Singh
- Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anmol Singh Pannu
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, Punjab, India
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50
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Le Berre C, Roda G, Nedeljkovic Protic M, Danese S, Peyrin-Biroulet L. Modern use of 5-aminosalicylic acid compounds for ulcerative colitis. Expert Opin Biol Ther 2019; 20:363-378. [DOI: 10.1080/14712598.2019.1666101] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Catherine Le Berre
- Inserm U954 and Department of Gastroenterology, Nancy University Hospital, Université de Lorraine, Vandoeuvre-lès-Nancy, France
- Institut des Maladies de l’Appareil Digestif, Nantes University Hospital, Nantes, France
| | - Giulia Roda
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Centre, Milan, Italy
| | | | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Centre, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Inserm U954 and Department of Gastroenterology, Nancy University Hospital, Université de Lorraine, Vandoeuvre-lès-Nancy, France
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