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Gisbert JP, Chaparro M. Common Mistakes in Managing Patients with Inflammatory Bowel Disease. J Clin Med 2024; 13:4795. [PMID: 39200937 PMCID: PMC11355176 DOI: 10.3390/jcm13164795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
Introduction: Errors are very common in medical practice and in particular, in the healthcare of patients with inflammatory bowel disease (IBD); however, most of these can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to this problem consists in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation for each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, elderly patients, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for a greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it is desirable to follow IBD patients in specialized units, which would undoubtedly be associated with higher-quality healthcare and a lower likelihood of errors in managing these patients.
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Affiliation(s)
- Javier P. Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain;
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Akbar A, Arnott I, Kennedy NA, Nolan J, Peake S, Whiteoak SR, Probert C, Fraser A, Cheshire A, Lewis A, Sugrue K, Laird S, Scott G. Recommendations for the optimal use of mesalazine in the management of patients with mild to moderate ulcerative colitis. Br J Hosp Med (Lond) 2021; 82:1-11. [PMID: 34726945 DOI: 10.12968/hmed.2021.0399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The 2021 National report from IBD UK included responses from over 10 000 patients with inflammatory bowel disease, over 70% of whom reported having at least one flare in the last 12 months. As the first-line treatment for patients with mild and moderate ulcerative colitis, the action and delivery mechanisms of mesalazine are crucial for successful management of the disease. The choice of the most appropriate formulation of mesalazine and securing patient concordance and adherence to treatment remains a challenge for healthcare professionals. This article details the outcome of a roundtable discussion involving a group of gastroenterology consultants and specialist nurses which considered the importance of ensuring that patients have individualised mesalazine therapy before escalation to other treatments and gives recommendations for the management of patients with mild or moderate ulcerative colitis.
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Affiliation(s)
- Ayesha Akbar
- Consultant Gastroenterologist, St Marks Hospital, Harrow, Middlesex, UK
| | - Ian Arnott
- Consultant Gastroenterologist, Western General Hospital, Edinburgh, UK
| | - Nicholas A Kennedy
- Consultant Gastroenterologist, Royal Devon & Exeter Hospital NHS Foundation Trust, Exeter, UK
| | - Jonathan Nolan
- Consultant Gastroenterologist, Kingston Hospital, Kingston Upon Thames, UK
| | - Simon Peake
- Consultant Gastroenterologist, Imperial College Healthcare NHS Trust, London, UK
| | - Simon R Whiteoak
- Consultant Gastroenterologist, University Hospitals Dorset, Bournemouth, UK
| | - Chris Probert
- Professor of Gastroenterology, University of Liverpool, Liverpool, UK
| | - Aileen Fraser
- IBD Advanced Clinical Practitioner, University Hospitals Bristol & Weston, UK
| | - Alex Cheshire
- Day Case Unit/Endoscopy Nurse Team Lead, Queen Mary's Hospital, St George's University Hospital Trust, London, UK
| | - Allyson Lewis
- IBD Specialist Nurse, Royal Gwent Hospital, Newport, UK
| | - Kathleen Sugrue
- Advanced Nurse Practitioner, Mercy University Hospital, Cork, Ireland
| | - Susan Laird
- IBD Clinical Nurse Specialist Team Lead, Queen Elizabeth University Hospital, Glasgow, UK
| | - Glyn Scott
- Consultant Nurse Gastroenterology/Endoscopy/IBD, East Kent Hospital, Canterbury, UK
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Murray A, Nguyen TM, Parker CE, Feagan BG, MacDonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2020; 8:CD000544. [PMID: 32856298 PMCID: PMC8094989 DOI: 10.1002/14651858.cd000544.pub5] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Oral 5-aminosalicylic acid (5-ASA; also known as mesalazine or mesalamine) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. In an earlier version of this review, we found that 5-ASA drugs were more effective than placebo for maintenance of remission of ulcerative colitis (UC), but had a significant therapeutic inferiority relative to SASP. In this version, we have rerun the search to bring the review up to date. OBJECTIVES To assess the efficacy, dose-responsiveness, and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent UC and to compare the efficacy and safety of once-daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. SEARCH METHODS We performed a literature search for studies on 11 June 2019 using MEDLINE, Embase, and the Cochrane Library. In addition, we searched review articles and conference proceedings. SELECTION CRITERIA We included randomized controlled trials with a minimum treatment duration of six months. We considered studies of oral 5-ASA therapy for treatment of participants with quiescent UC compared with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose-ranging studies. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were adherence, adverse events (AE), serious adverse events (SAE), withdrawals due to AEs, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus SASP, once-daily dosing versus conventional dosing, 5-ASA (balsalazide, Pentasa, and olsalazine) versus comparator 5-ASA formulation (Asacol and Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence. MAIN RESULTS The search identified 44 studies (9967 participants). Most studies were at low risk of bias. Ten studies were at high risk of bias. Seven of these studies were single-blind and three were open-label. 5-ASA is more effective than placebo for maintenance of clinical or endoscopic remission. About 37% (335/907) of 5-ASA participants relapsed at six to 12 months compared to 55% (355/648) of placebo participants (RR 0.68, 95% CI 0.61 to 0.76; 8 studies, 1555 participants; high-certainty evidence). Adherence to study medication was not reported for this comparison. SAEs were reported in 1% (6/550) of participants in the 5-ASA group compared to 2% (5/276) of participants in the placebo group at six to 12 months (RR 0.60, 95% CI 0.19 to 1.84; 3 studies, 826 participants; low-certainty evidence). There is probably little or no difference in AEs at six to 12 months' follow-up (RR 0.93, 95% CI 0.73 to 1.18; 5 studies, 1132 participants; moderate-certainty evidence). SASP is more effective than 5-ASA for maintenance of remission. About 48% (416/871) of 5-ASA participants relapsed at six to 18 months compared to 43% (336/784) of SASP participants (RR 1.14, 95% CI 1.03 to 1.27; 12 studies, 1655 participants; high-certainty evidence). Adherence to study medication and SAEs were not reported for this comparison. There is probably little or no difference in AEs at six to 12 months' follow-up (RR 1.07, 95% CI 0.82 to 1.40; 7 studies, 1138 participants; moderate-certainty evidence). There is little or no difference in clinical or endoscopic remission rates between once-daily and conventionally dosed 5-ASA. About 37% (717/1939) of once-daily participants relapsed over 12 months compared to 39% (770/1971) of conventional-dosing participants (RR 0.94, 95% CI 0.88 to 1.01; 10 studies, 3910 participants; high-certainty evidence). There is probably little or no difference in medication adherence rates. About 10% (106/1152) of participants in the once-daily group failed to adhere to their medication regimen compared to 8% (84/1154) of participants in the conventional-dosing group (RR 1.18, 95% CI 0.72 to 1.93; 9 studies, 2306 participants; moderate-certainty evidence). About 3% (41/1587) of participants in the once-daily group experienced a SAE compared to 2% (35/1609) of participants in the conventional-dose group at six to 12 months (RR 1.20, 95% CI 0.77 to 1.87; moderate-certainty evidence). There is little or no difference in the incidence of AEs at six to 13 months' follow-up (RR 0.98, 95% CI 0.92 to 1.04; 8 studies, 3497 participants; high-certainty evidence). There may be little or no difference in the efficacy of different 5-ASA formulations. About 44% (158/358) of participants in the 5-ASA group relapsed at six to 18 months compared to 41% (142/349) of participants in the 5-ASA comparator group (RR 1.08, 95% CI 0.91 to 1.28; 6 studies, 707 participants; low-certainty evidence). AUTHORS' CONCLUSIONS There is high-certainty evidence that 5-ASA is superior to placebo for maintenance therapy in UC. There is high-certainty evidence that 5-ASA is inferior compared to SASP. There is probably little or no difference between 5-ASA and placebo, and 5-ASA and SASP in commonly reported AEs such as flatulence, abdominal pain, nausea, diarrhea, headache, and dyspepsia. Oral 5-ASA administered once daily has a similar benefit and harm profile as conventional dosing for maintenance of remission in quiescent UC.
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Affiliation(s)
- Alistair Murray
- Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada
| | | | | | - Brian G Feagan
- Robarts Clinical Trials, London, Canada
- Department of Medicine, University of Western Ontario, London, Canada
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada
| | - John K MacDonald
- Department of Medicine, University of Western Ontario, London, Canada
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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: 1517] [Impact Index Per Article: 252.8] [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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6
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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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Olaisen M, Spigset O, Flatberg A, Granlund AVB, Brede WR, Albrektsen G, Røyset ES, Gilde B, Sandvik AK, Martinsen TC, Fossmark R. Mucosal 5-aminosalicylic acid concentration, drug formulation and mucosal microbiome in patients with quiescent ulcerative colitis. Aliment Pharmacol Ther 2019; 49:1301-1313. [PMID: 30895635 PMCID: PMC6593792 DOI: 10.1111/apt.15227] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 01/18/2019] [Accepted: 02/22/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND 5-aminosalicylic acid (5-ASA) is the first-line therapy for ulcerative colitis (UC). 5-ASA acts locally in the colonic mucosa by numerous proposed mechanisms, and is metabolised by N-acetyltransferase (NAT). Large variations in mucosal 5-ASA concentrations have been reported, but the underlying mechanisms are not understood. AIM To study the relationship between 5-ASA concentration, 5-ASA formulation, NAT genotype and bacterial microbiome in patients with UC. METHODS Patients with quiescent UC, using monotherapy of Mezavant (n = 18), Asacol (n = 14) or Pentasa (n = 10), 4.0-4.8 g/day were included. 5-ASA was measured in colonic mucosal biopsies and serum by ultra-high performance liquid chromatography. NAT genotypes were determined by Sanger sequencing. Bacterial microbiome was sequenced from faeces and mucosa by 16S rRNA sequencing using Illumina Miseq. RESULTS Mezavant provided the highest mucosal 5-ASA levels (geometric mean 2.39 ng/mg), followed by Asacol (1.60 ng/mg, 33% lower, P = 0.50) and Pentasa (0.57 ng/mg, 76% lower, P = 0.033). Mucosal 5-ASA concentration was not associated with NAT genotype, but serum 5-ASA concentration and NAT1 genotype was associated (P = 0.044). Mucosal 5-ASA concentration was positively associated with mucosal bacterial diversity (P = 0.0005) and bacterial composition. High mucosal 5-ASA concentration was related to reduced abundance of pathogenic bacteria such as Proteobacteria, and increased abundance of several favourable bacteria such as Faecalibacterium. CONCLUSIONS Mucosal 5-ASA concentration is positively associated with bacterial diversity and a mucosal bacterial composition that are perceived favourable in UC. Mezavant yielded higher mucosal 5-ASA concentrations than Pentasa. 5-ASA may have beneficial effects on the mucosal microbiome, and high concentrations possibly amend dysbiosis in UC.
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Affiliation(s)
- Maya Olaisen
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health SciencesNTNU – Norwegian University of Science and TechnologyTrondheimNorway,Department of Gastroenterology, Clinic of MedicineSt. Olav's Hospital, Trondheim University HospitalTrondheimNorway
| | - Olav Spigset
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health SciencesNTNU – Norwegian University of Science and TechnologyTrondheimNorway,Department of Clinical Pharmacology, Clinic of Laboratory MedicineSt. Olav's Hospital, Trondheim University HospitalTrondheimNorway
| | - Arnar Flatberg
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health SciencesNTNU – Norwegian University of Science and TechnologyTrondheimNorway
| | - Atle van Beelen Granlund
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health SciencesNTNU – Norwegian University of Science and TechnologyTrondheimNorway,Centre of Molecular Inflammation ResearchNorwegian University of Science and TechnologyTrondheimNorway
| | - Wenche Rødseth Brede
- Department of Clinical Pharmacology, Clinic of Laboratory MedicineSt. Olav's Hospital, Trondheim University HospitalTrondheimNorway
| | - Grethe Albrektsen
- Department of Public Health and Nursing, Faculty of Medicine and Health ScienceNTNU – Norwegian University of Science and TechnologyTrondheimNorway
| | - Elin Synnøve Røyset
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health SciencesNTNU – Norwegian University of Science and TechnologyTrondheimNorway,Department of Pathology, Clinic of Laboratory MedicineSt. Olav's Hospital, Trondheim University HospitalTrondheimNorway
| | - Bodil Gilde
- Department of Medical Genetics, Clinic of Laboratory MedicineSt. Olav's Hospital, Trondheim University HospitalTrondheimNorway
| | - Arne Kristian Sandvik
- Department of Gastroenterology, Clinic of MedicineSt. Olav's Hospital, Trondheim University HospitalTrondheimNorway,Centre of Molecular Inflammation ResearchNorwegian University of Science and TechnologyTrondheimNorway
| | - Tom Christian Martinsen
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health SciencesNTNU – Norwegian University of Science and TechnologyTrondheimNorway,Department of Gastroenterology, Clinic of MedicineSt. Olav's Hospital, Trondheim University HospitalTrondheimNorway
| | - Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health SciencesNTNU – Norwegian University of Science and TechnologyTrondheimNorway,Department of Gastroenterology, Clinic of MedicineSt. Olav's Hospital, Trondheim University HospitalTrondheimNorway
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Ahmad H, Kumar VL. Pharmacotherapy of ulcerative colitis - current status and emerging trends. J Basic Clin Physiol Pharmacol 2019; 29:581-592. [PMID: 30089097 DOI: 10.1515/jbcpp-2016-0014] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 05/04/2018] [Indexed: 12/23/2022]
Abstract
Ulcerative colitis (UC) is a chronic mucosal inflammation of the large intestine restricted to the rectum and colon. Its clinical course follows an intermittent pattern with episodes of relapse, followed by remission and eventually resulting in mucosal damage. Although there is no permanent cure for UC, the currently available pharmacotherapy aims to induce and maintain clinical remission, promote the healing of colonic mucosa and avert any surgical intervention. The conventional drug therapy comprising of 5-aminosalicylates, thiopurines and corticosteroids has advanced recently in terms of formulations and dosing schedule, resulting in improved efficacy, safety and compliance. Calcineurin inhibitors, such as cyclosporin and tacrolimus, have emerged as steroid sparing agents. The treatment paradigm of UC patients who are refractory to conventional drugs has changed in view of the availability of biologics. Currently, there are four biologics approved by the US FDA for the treatment of UC, namely, infliximab, adalimumab, golimumab and vedolizumab, and several others are undergoing clinical trial. In this comprehensive review, the advantages and limitations of the medical therapy of UC are elaborated with an emphasis on the pharmacokinetic and pharmacodynamic aspects of the drugs.
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Affiliation(s)
- Hilal Ahmad
- Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Vijay L Kumar
- Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
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9
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Doherty G, Katsanos KH, Burisch J, Allez M, Papamichael K, Stallmach A, Mao R, Berset IP, Gisbert JP, Sebastian S, Kierkus J, Lopetuso L, Szymanska E, Louis E. European Crohn's and Colitis Organisation Topical Review on Treatment Withdrawal ['Exit Strategies'] in Inflammatory Bowel Disease. J Crohns Colitis 2018; 12:17-31. [PMID: 28981623 DOI: 10.1093/ecco-jcc/jjx101] [Citation(s) in RCA: 143] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 07/31/2017] [Indexed: 12/12/2022]
Abstract
Clinically effective therapies now exist for remission maintenance in both ulcerative colitis [UC] and Crohn's Disease [CD]. For each major class of IBD medications [5-aminosalicyclates, immunomodulators, and biologic agents], used alone or in combination, there is a risk of relapse following reduction or cessation of treatment. A consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the published literature and agreed a series of consensus practice points. The objective of the expert consensus is to provide evidence-based guidance for clinical practice so that physicians can make informed decisions in partnership with their patients. The likelihood of relapse with stopping each class of IBD medication is reviewed. Factors associated with an altered risk of relapse with withdrawal are evaluated, and strategies to monitor and allow early identification of relapse are considered. In general, patients in clinical, biochemical, and endoscopic remission are more likely to remain well when treatments are stopped. Reintroduction of the same treatment is usually, but not always, successful. The decision to stop a treatment needs to be individualized, and shared decision making with the patient should take place.
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Affiliation(s)
- Glen Doherty
- Centre for Colorectal Disease, St Vincent's University Hospital & University College Dublin, Dublin, Ireland
| | - Konstantinos H Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Matthieu Allez
- Department of Gastroenterology and Hepatology, Hôpital Saint-Louis, APHP, INSERM UMRS 1160, Université Denis Diderot, Paris, France
| | | | - Andreas Stallmach
- Department of Internal Medicine IV [Gastroenterology, Hepatology and Infectious Disease], University Hospital Jena, Jena, Germany
| | - Ren Mao
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ingrid Prytz Berset
- Gastroenterology Department, Alesund Hospital, Helse More Romsdal Hospital Trust, Alesund, Norway
| | - Javier P Gisbert
- Department of Gastroenterology, Hospital Universitario de la Princesa, Instituto de Investigaciun Sanitaria Princesa (IIS-IP) and Centro de Investigaciun Biomédica en Red de Enfermedades Heprticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Shaji Sebastian
- IBD Unit, Department of Gastroenterology, Hull & East Yorkshire Hospitals NHS Trust, Hull, UK
| | - Jaroslaw Kierkus
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Children's Memorial Health Institute, Warsaw, Poland
| | - Loris Lopetuso
- Department of Gastroenterology and Internal Medicine, Catholic University of Rome-A. Gemelli Hospital, Rome, Italy
| | - Edyta Szymanska
- Department of Pediatrics, Nutrition, and Metabolic Disorders, Children's Memorial Health Institute, Warsaw, Poland
| | - Edouard Louis
- Department of Gastroenterology, CHU Liège, Sart Tilman, Liège, Belgium
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Wang Y, Parker CE, Feagan BG, MacDonald JK, Cochrane IBD Group. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2016; 2016:CD000544. [PMID: 27158764 PMCID: PMC7045447 DOI: 10.1002/14651858.cd000544.pub4] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Oral 5-aminosalicylic (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs were more effective than placebo but had a statistically significant therapeutic inferiority relative to SASP. This updated review includes more recent studies and evaluates the effectiveness, dose-responsiveness, and safety of 5-ASA preparations used for maintenance of remission in quiescent ulcerative colitis. OBJECTIVES The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent ulcerative colitis. A secondary objective was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. SEARCH METHODS A literature search for relevant studies (inception to 9 July 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. SELECTION CRITERIA Studies were accepted for analysis if they were randomized controlled trials with a minimum treatment duration of six months. Studies of oral 5-ASA therapy for treatment of patients with quiescent ulcerative colitis compared with placebo, SASP or other 5-ASA formulations were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose ranging studies were also considered for inclusion. DATA COLLECTION AND ANALYSIS The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes included adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA formulation, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol and Salofalk). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. MAIN RESULTS Forty-one studies (8928 patients) were included. The majority of included studies were rated as low risk of bias. Ten studies were rated at high risk of bias. Seven of these studies were single-blind and three studies were open-label. However, two open-label studies and four of the single-blind studies utilized investigator performed endoscopy as an endpoint, which may protect against bias. 5-ASA was significantly superior to placebo for maintenance of clinical or endoscopic remission. Forty-one per cent of 5-ASA patients relapsed compared to 58% of placebo patients (7 studies, 1298 patients; RR 0.69, 95% CI 0.62 to 0.77). There was a trend towards greater efficacy with higher doses of 5-ASA with a statistically significant benefit for the 1 to 1.9 g/day (RR 0.65; 95% CI 0.56 to 0.76) and the > 2 g/day subgroups (RR 0.73, 95% CI 0.60 to 0.89). SASP was significantly superior to 5-ASA for maintenance of remission. Forty-eight per cent of 5-ASA patients relapsed compared to 43% of SASP patients (12 studies, 1655 patients; RR 1.14, 95% CI 1.03 to 1.27). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome for the placebo and SASP-controlled studies was high. No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Twenty-nine per cent of once daily patients relapsed over 12 months compared to 31% of conventionally dosed patients (8 studies, 3127 patients; RR 0.91, 95% CI 0.82 to 1.01). Eleven per cent of patients in the once daily group failed to adhere to their medication regimen compared to 9% of patients in the conventional dosing group (6 studies, 1462 patients; RR 1.22, 95% CI 0.91 to 1.64). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Forty-four per cent of patients in the 5-ASA group relapsed compared to 41% of patients in the 5-ASA comparator group (6 studies, 707 patients; RR 1.08, 95% CI 0.91 to 1.28). A pooled analysis of two studies showed no statistically significant difference in efficacy between Balsalazide 6 g and 3 g/day. Twenty-three per cent of patients in the 6 g/day group relapsed compared to 33% of patients in the 3 g/day group (216 patients; RR 0.76; 95% CI 0.45 to 2.79). One study found Balsalazide 4 g to be superior to 2 g/day. Thirty-seven per cent of patients in the 4 g/day Balsalazide group relapsed compared to 55% of patients in the 2 g/day group (133 patients; RR 0.66; 95% CI 0.45 to 0.97). One study found a statistically significant difference between Salofalk granules 3 g and 1.5 g/day. Twenty-five per cent of patients in the Salofalk 3 g/day group relapsed compared to 39% of patients in the 1.5 g/day group (429 patients; RR 0.65; 95% CI 0.49 to 0.86). Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache, dyspepsia, and nasopharyngitis. There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, 5-ASA and SASP, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulations and 5-ASA dose ranging studies. The trials that compared 5-ASA and SASP may have been biased in favour of SASP because most trials enrolled patients known to be tolerant to SASP which may have minimized SASP-related adverse events. AUTHORS' CONCLUSIONS 5-ASA was superior to placebo for maintenance therapy in ulcerative colitis. However, 5-ASA had a statistically significant therapeutic inferiority relative to SASP. Oral 5-ASA administered once daily is as effective and safe as conventional dosing for maintenance of remission in quiescent ulcerative colitis. There does not appear to be any difference in efficacy or safety between the various formulations of 5-ASA. Patients with extensive ulcerative colitis or with frequent relapses may benefit from a higher dose of maintenance therapy. High dose therapy appears to be as safe as low dose and is not associated with a higher incidence of adverse events.
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Affiliation(s)
- Yongjun Wang
- University of Western OntarioSchulich School of Medicine & DentistryLondonONCanada
| | - Claire E Parker
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
| | - Brian G Feagan
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
| | - John K MacDonald
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
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11
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Wang Y, Parker CE, Feagan BG, MacDonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2016. [PMID: 27158764 DOI: 10.1002/14651858.cd000544.pub4.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Oral 5-aminosalicylic (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs were more effective than placebo but had a statistically significant therapeutic inferiority relative to SASP. This updated review includes more recent studies and evaluates the effectiveness, dose-responsiveness, and safety of 5-ASA preparations used for maintenance of remission in quiescent ulcerative colitis. OBJECTIVES The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent ulcerative colitis. A secondary objective was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. SEARCH METHODS A literature search for relevant studies (inception to 9 July 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. SELECTION CRITERIA Studies were accepted for analysis if they were randomized controlled trials with a minimum treatment duration of six months. Studies of oral 5-ASA therapy for treatment of patients with quiescent ulcerative colitis compared with placebo, SASP or other 5-ASA formulations were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose ranging studies were also considered for inclusion. DATA COLLECTION AND ANALYSIS The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes included adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA formulation, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol and Salofalk). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. MAIN RESULTS Forty-one studies (8928 patients) were included. The majority of included studies were rated as low risk of bias. Ten studies were rated at high risk of bias. Seven of these studies were single-blind and three studies were open-label. However, two open-label studies and four of the single-blind studies utilized investigator performed endoscopy as an endpoint, which may protect against bias. 5-ASA was significantly superior to placebo for maintenance of clinical or endoscopic remission. Forty-one per cent of 5-ASA patients relapsed compared to 58% of placebo patients (7 studies, 1298 patients; RR 0.69, 95% CI 0.62 to 0.77). There was a trend towards greater efficacy with higher doses of 5-ASA with a statistically significant benefit for the 1 to 1.9 g/day (RR 0.65; 95% CI 0.56 to 0.76) and the > 2 g/day subgroups (RR 0.73, 95% CI 0.60 to 0.89). SASP was significantly superior to 5-ASA for maintenance of remission. Forty-eight per cent of 5-ASA patients relapsed compared to 43% of SASP patients (12 studies, 1655 patients; RR 1.14, 95% CI 1.03 to 1.27). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome for the placebo and SASP-controlled studies was high. No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Twenty-nine per cent of once daily patients relapsed over 12 months compared to 31% of conventionally dosed patients (8 studies, 3127 patients; RR 0.91, 95% CI 0.82 to 1.01). Eleven per cent of patients in the once daily group failed to adhere to their medication regimen compared to 9% of patients in the conventional dosing group (6 studies, 1462 patients; RR 1.22, 95% CI 0.91 to 1.64). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Forty-four per cent of patients in the 5-ASA group relapsed compared to 41% of patients in the 5-ASA comparator group (6 studies, 707 patients; RR 1.08, 95% CI 0.91 to 1.28). A pooled analysis of two studies showed no statistically significant difference in efficacy between Balsalazide 6 g and 3 g/day. Twenty-three per cent of patients in the 6 g/day group relapsed compared to 33% of patients in the 3 g/day group (216 patients; RR 0.76; 95% CI 0.45 to 2.79). One study found Balsalazide 4 g to be superior to 2 g/day. Thirty-seven per cent of patients in the 4 g/day Balsalazide group relapsed compared to 55% of patients in the 2 g/day group (133 patients; RR 0.66; 95% CI 0.45 to 0.97). One study found a statistically significant difference between Salofalk granules 3 g and 1.5 g/day. Twenty-five per cent of patients in the Salofalk 3 g/day group relapsed compared to 39% of patients in the 1.5 g/day group (429 patients; RR 0.65; 95% CI 0.49 to 0.86). Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache, dyspepsia, and nasopharyngitis. There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, 5-ASA and SASP, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulations and 5-ASA dose ranging studies. The trials that compared 5-ASA and SASP may have been biased in favour of SASP because most trials enrolled patients known to be tolerant to SASP which may have minimized SASP-related adverse events. AUTHORS' CONCLUSIONS 5-ASA was superior to placebo for maintenance therapy in ulcerative colitis. However, 5-ASA had a statistically significant therapeutic inferiority relative to SASP. Oral 5-ASA administered once daily is as effective and safe as conventional dosing for maintenance of remission in quiescent ulcerative colitis. There does not appear to be any difference in efficacy or safety between the various formulations of 5-ASA. Patients with extensive ulcerative colitis or with frequent relapses may benefit from a higher dose of maintenance therapy. High dose therapy appears to be as safe as low dose and is not associated with a higher incidence of adverse events.
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Affiliation(s)
- Yongjun Wang
- Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada
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12
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Leitner GC, Vogelsang H. Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World J Gastrointest Pharmacol Ther 2016; 7:5-20. [PMID: 26855808 PMCID: PMC4734954 DOI: 10.4292/wjgpt.v7.i1.5] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 12/14/2015] [Accepted: 01/08/2016] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.
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13
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Liu JL, Shen H, Gu PQ, Zheng K, Liu YJ, Shen TH. Therapeutic effects of Qingchang Huashi Recipe combined with mesalazine in patients with distal ulcerative colitis. Shijie Huaren Xiaohua Zazhi 2015; 23:5715-5721. [DOI: 10.11569/wcjd.v23.i35.5715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the clinical efficacy of Qingchang Huashi Recipe combined with mesalazine in patients with mild to moderate distal ulcerative colitis.
METHODS: Forty-eight patients with mild to moderate distal ulcerative colitis were randomly divided into two groups: a treatment group and a control group. The treatment group was treated with Qingchang Huashi Recipe (traditional Chinese Medicine enema) combined with mesalazine, and the control group was treated with mesalazine only. The period of treatment was 12 weeks. The effective rate, the rates of disappearance of main symptoms, Sutherland disease activity index (DAI), erythrocyte sedimentation rate (ESR) and blood platelet (PLT) count were compared between the two groups before and after treatment. Adverse reactions were also recorded.
RESULTS: After 12 weeks of treatment, the total effective rate in the treatment group was significantly higher than that in the control group (P < 0.05). The rates of disappearance of diarrhea and hematochezia were significantly higher in the treatment group than in the control group (P < 0.05). DAI was significantly lower in the treatment group than in the control group (P < 0.01). ESR and PLT count were significantly lower in the treatment group than in the control group (P < 0.05). In two groups there was one patient each complaining with abdominal discomfort, dizziness, nausea or other symptoms, which relieved spontaneously. One patient of the control group had moderately increased alanine aminotransferase and aspartate transaminase, which returned to normal after symptomatic treatment.
CONCLUSION: Qingchang Huashi Recipe combined with mesalazine can significantly improve symptoms and reduce DAI, ESR and PLT in patients with mild to moderate distal ulcerative colitis. The combination therapy is effective and safe and its short-term clinical efficacy is superior to that of mesalazine alone.
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14
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Dignass A, Lindsay JO, Sturm A, Windsor A, Colombel JF, Allez M, d'Haens G, d'Hoore A, Mantzanaris G, Novacek G, Öresland T, Reinisch W, Sans M, Stange E, Vermeire S, Travis S, van Assche G. [Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management (Spanish version)]. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2015; 80:32-73. [PMID: 25769217 DOI: 10.1016/j.rgmx.2014.10.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 10/23/2014] [Indexed: 02/06/2023]
Affiliation(s)
- A Dignass
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso.
| | | | - A Sturm
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - A Windsor
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - J-F Colombel
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - M Allez
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - G d'Haens
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - A d'Hoore
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - G Mantzanaris
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - G Novacek
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - T Öresland
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - W Reinisch
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - M Sans
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - E Stange
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - S Vermeire
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
| | - S Travis
- Contribuyeron por igual a este trabajo; Coordinadores del Consenso
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15
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Five-aminosalicylic Acid: an update for the reappraisal of an old drug. Gastroenterol Res Pract 2015; 2015:456895. [PMID: 25685145 PMCID: PMC4320793 DOI: 10.1155/2015/456895] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 12/29/2014] [Indexed: 12/17/2022] Open
Abstract
Inflammatory bowel disease (IBD) comprises several conditions with chronic or recurring immune response and inflammation of the gastrointestinal apparatus, of which ulcerative colitis and Crohn's disease are the commonest forms. This disease has a significant prevalence and it is of an unknown aethiology. Five-aminosalicylic acid (5-ASA) and its derivatives are among the oldest drugs approved for the treatment of the IBD. In this review we reapprise aspects of 5-ASA mechanism of action, safety, and efficacy that in our opinion make it a valuable drug that can be fruitfully tailored in personalised treatments as a therapeutic option alongside other immune-modifying agents.
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16
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Viscido A, Capannolo A, Latella G, Caprilli R, Frieri G. Nanotechnology in the treatment of inflammatory bowel diseases. J Crohns Colitis 2014; 8:903-18. [PMID: 24686095 DOI: 10.1016/j.crohns.2014.02.024] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 02/26/2014] [Accepted: 02/26/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Treatment of inflammatory bowel diseases (IBD) is only aimed to block or inhibit the pathogenetic steps of the inflammatory cascade. Side effects of systemic therapies, poor targeting of orally administered topical drug and low adherence to prescription represent frequent therapeutic challenges. Recent observations suggest that nanotechnology could provide amazing advantage in this field since particles having dimension in the nanometer scale (nanoparticles) can modify pharmacokinetic step of biologic and conventional therapeutic agents with a better delivery of drugs within the intestinal inflammatory cells. The aim of this review was to provide the clinician with an insight into the potential role of nanotechnology in the treatment of IBD. METHODS A systematic search (PubMed) for experimental studies on the treatment of intestinal inflammation using nanotechnology for the delivery of drugs. RESULTS AND CONCLUSIONS The size of the pharmaceutical formulation is inversely related to specificity for inflammation. Nanoparticles can penetrate epithelial and inflammatory cells resulting in much higher, effective and long-acting concentrations than can be obtained using conventional delivery systems. From a practical point of view, this should lead to improvements in both efficacy and adherence to treatment, providing patients with the prospect of stable and prolonged remissions with reduced drug loadings. Reduced systemic side effects could also be expected.
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Affiliation(s)
- Angelo Viscido
- Gastroenterology Unit, Department of Life, Health, & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Annalisa Capannolo
- Gastroenterology Unit, Department of Life, Health, & Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health, & Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | | | - Giuseppe Frieri
- Gastroenterology Unit, Department of Life, Health, & Environmental Sciences, University of L'Aquila, L'Aquila, Italy
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17
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O'Connor A, Moss AC. Current and emerging maintenance therapies for ulcerative colitis. Expert Rev Gastroenterol Hepatol 2014; 8:359-68. [PMID: 24650224 DOI: 10.1586/17474124.2014.896193] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Ulcerative colitis (UC) is a chronic idiopathic intestinal disease that requires life-long maintenance therapy to maintain clinical remission. This article reviews the current literature on maintenance treatments in UC. It examines the natural history of the condition and the proposed benefits of treatment. These include improving quality of life parameters, decreasing corticosteroid intake, the prevention of relapse, the prevention of colorectal cancer and the avoidance of colectomy. The immunosuppressive era appears to be reducing the need for elective colectomy in UC. The article explores the classes of drug currently used for maintenance of UC, reviews the literature around adherence issues, and summarizes emerging agents in this space.
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Affiliation(s)
- Anthony O'Connor
- Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
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18
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D’Incà R, Paccagnella M, Cardin R, Pathak S, Baldo V, Giron MC, Sturniolo GC. 5-ASA colonic mucosal concentrations resulting from different pharmaceutical formulations in ulcerative colitis. World J Gastroenterol 2013; 19:5665-5670. [PMID: 24039359 PMCID: PMC3769903 DOI: 10.3748/wjg.v19.i34.5665] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Accepted: 05/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the mucosal concentrations of 5-aminosalicylic acid (5-ASA) resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.
METHODS: The study included 130 inflammatory bowel disease (IBD) patients receiving 5-ASA as pH-dependent-release formulations (73 patients), time-dependent-release formulations (11 patients), or pro-drugs (18 patients). In addition, 28 patients were receiving topical treatment (2-4 g/d) with pH-dependent-release formulations. Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy. The 5-ASA concentrations (ng/mg) were measured in tissue homogenates using high-pressure liquid chromatography with electrochemical detection. The t test and Mann-Whitney test, when appropriate, were used for statistical analysis.
RESULTS: Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA (51.75 ± 5.72 ng/mg) compared with patients receiving pro-drugs (33.35 ± 5.78 ng/mg, P = 0.01) or time-dependent-release formulations (38.24 ± 5.53 ng/mg, P = 0.04). Patients with endoscopic remission had significantly higher mucosal concentrations of 5-ASA than patients with active disease (60.14 ± 7.95 ng/mg vs 35.66 ± 5.68 ng/mg, P = 0.02). Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation (67.53 ± 9.22 ng/mg vs 35.53 ± 5.63 ng/mg, P < 0.001). Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone (72.33 ± 11.23 ng/mg vs 51.75 ± 5.72 ng/mg, P = 0.03).
CONCLUSION: IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation, and the highest mean concentration was achieved using pH-dependent-release formulations.
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19
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Lipka S, Katz S, Kaur N. "One more time" 5-ASA retrial after a glucocorticosteroid induced remission in moderate to severe ulcerative colitis: a prospective community practice experience. J Crohns Colitis 2013; 7:342-3. [PMID: 22871515 DOI: 10.1016/j.crohns.2012.07.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2012] [Accepted: 07/16/2012] [Indexed: 02/08/2023]
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Wang YL, Li J, Liu PW. Refractory distal ulcerative colitis: Clinical manifestations and treatment. Shijie Huaren Xiaohua Zazhi 2013; 21:454-458. [DOI: 10.11569/wcjd.v21.i5.454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the clinical features and treatment of distal ulcerative colitis (DUC) and to analyze probable reasons and optimal therapeutic regimens for refractory DUC.
METHODS: Clinical data for 145 DUC patients who were treated at the Affiliated Yijishan Hospital of Wannan Medical College from January 2005 to December 2011 were retrospectively analyzed. Based on the response to traditional treatments, the patients were divided into either an effective group or a refractory group. The two groups were compared in clinical and laboratory examination results to analyze probable reasons and optimal therapeutic regimens for refractory DUC.
RESULTS: Of 145 DUC patients, 117 were eligible for evaluation, and 26 of 117 patients were confirmed to have refractory DUC. The percentages of patients with abdominal distention and abdominal pain or elevated white blood cell count differed significantly between the refractory group and effective group (42.3% vs 22.0%, P = 0.038; 30.8% vs 12.1%, P = 0.035), while no significant differences were found in bloody stools, diarrhea, extraintestinal manifestations, C-reactive protein, blood sedimentation between the two groups (all P > 0.05). Of all 117 cases, 43 were found to have rectitis (including 10 refractory cases), and 74 were found to have sigmoiditis (including 16 refractory cases). No significant difference was found between the two groups in the location of the lesions (P > 0.05). Of 26 refractory cases, only 1 was treated by surgery, and the others were treated by intravenous hormone therapy, addition of new dosage form of 5-ASA, or proper laxatives to gain relief.
CONCLUSION: Diarrhea and bloody stools are the most common clinical symptoms of DUC. Significantly elevated leukocyte count can be expected to be an important factor for evaluating treatment outcome of DUC. Refractory DUC can be treated by intensification therapy, addition of new dosage form of 5-ASA, proper laxatives, or surgery to gain relief.
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Probert C. Steroids and 5-aminosalicylic acids in moderate ulcerative colitis: addressing the dilemma. Therap Adv Gastroenterol 2013; 6:33-8. [PMID: 23320048 PMCID: PMC3539295 DOI: 10.1177/1756283x12461395] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Steroids have been a mainstay of ulcerative colitis (UC) therapy for many years, based on a thoroughly established efficacy profile for the induction of remission. However, in light of the considerable side effects and negative perceptions they carry, it is important to ensure such treatments are used as effectively as possible. For severe UC, the need for steroids is rarely questioned, and rightly so; it is for moderate UC that the role of steroids should be considered. Both patients and clinicians place a high importance on rapid, effective resolution of symptoms, yet at the same time wish to avoid unnecessary side effects. Through consideration of the available evidence, it becomes clear that both steroids and high-dose 5-aminosalicylic acid (5-ASA) are supported by robust trials demonstrating their efficacy. Indeed, both therapies have been shown to give rise to resolution of symptoms after 2 weeks in many patients. However, a paucity of head-to-head comparisons makes conclusive interpretation challenging. This paper therefore presents a practical approach, which builds on the available evidence and is developed from informed discussions with patients. This approach involves initiating therapy with high-dose 5-ASA, followed by a review of symptom improvements after 2-3 weeks. Steroids can then be introduced, when needed, with minimal delay. In this way, symptoms can be resolved rapidly, yet many patients may avoid unpleasant side effects.
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Affiliation(s)
- Chris Probert
- Department of Gastroenterology, The Henry Wellcome Laboratory, Institute of Translational Medicine, University of Liverpool, Nuffield Building, Crown Street, Liverpool L69 3GE, UK
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Dignass A, Lindsay JO, Sturm A, Windsor A, Colombel JF, Allez M, D'Haens G, D'Hoore A, Mantzaris G, Novacek G, Oresland T, Reinisch W, Sans M, Stange E, Vermeire S, Travis S, Van Assche G. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis 2012; 6:991-1030. [PMID: 23040451 DOI: 10.1016/j.crohns.2012.09.002] [Citation(s) in RCA: 700] [Impact Index Per Article: 53.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2012] [Accepted: 09/03/2012] [Indexed: 02/07/2023]
Affiliation(s)
- Axel Dignass
- Department of Medicine 1, Agaplesion Markus Hospital, Wilhelm-Epstein-Str. 4, D-60431 Frankfurt/Main, Germany.
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Feagan BG, Macdonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2012; 10:CD000544. [PMID: 23076890 DOI: 10.1002/14651858.cd000544.pub3] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Oral 5-aminosalicylic (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs were more effective than placebo but had a statistically significant therapeutic inferiority relative to SASP. This updated review includes more recent studies and evaluates the effectiveness, dose-responsiveness, and safety of 5-ASA preparations used for maintenance of remission in quiescent ulcerative colitis. OBJECTIVES The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent ulcerative colitis. A secondary objective was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. SEARCH METHODS A literature search for relevant studies (inception to January 20, 2012) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. SELECTION CRITERIA Studies were accepted for analysis if they were randomized controlled trials with a minimum treatment duration of six months. Studies of oral 5-ASA therapy for treatment of patients with quiescent ulcerative colitis compared with placebo, SASP or other 5-ASA formulations were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose ranging studies were also considered for inclusion. DATA COLLECTION AND ANALYSIS The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes included adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA formulation, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol and Salofalk). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention to treat basis. MAIN RESULTS Thirty-eight studies (8127 patients) were included. The majority of included studies were rated as low risk of bias. Eight studies were rated at high risk of bias. Six of these studies were single-blind and two studies were open-label. However, the two open-label studies and four of the single-blind studies utilized investigator performed endoscopy as an endpoint, which may protect against bias. 5-ASA was significantly superior to placebo for maintenance of clinical or endoscopic remission. Forty-one per cent of 5-ASA patients relapsed compared to 58% of placebo patients (7 studies, 1298 patients; RR 0.69, 95% CI 0.62 to 0.77). There was a trend towards greater efficacy with higher doses of 5-ASA with a statistically significant benefit for the 1 to 1.9 g/day (RR 0.65; 95% CI 0.56 to 0.76) and the > 2 g/day subgroups (RR 0.73, 95% CI 0.60 to 0.89). SASP was significantly superior to 5-ASA for maintenance of remission. Forty-eight per cent of 5-ASA patients relapsed compared to 43% of SASP patients (12 studies, 1655 patients; RR 1.14, 95% CI 1.03 to 1.27). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome for the placebo and SASP-controlled studies was high. No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Twenty-nine per cent of once daily patients relapsed over 12 months compared to 31% of conventionally dosed patients (7 studies, 2826 patients; RR 0.92, 95% CI 0.83 to 1.03). Fourteen per cent of patients in the once daily group failed to adhere to their medication regimen compared to 11% of patients in the conventional dosing group (5 studies, 1161 patients; RR 1.21, 95% CI 0.90 to 1.63). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Thirty-eight per cent of patients in the 5-ASA group relapsed compared to 37% of patients in the 5-ASA comparator group (5 studies, 457 patients; RR 1.01, 95% CI 0.80 to 1.28). A pooled analysis of two studies showed no statistically significant difference in efficacy between Balsalazide 6 g and 3 g/day. Twenty-three per cent of patients in the 6 g/day group relapsed compared to 33% of patients in the 3 g/day group (216 patients; RR 0.72; 95% CI 0.46 to 1.13). One study found Balsalazide 4 g to be superior to 2 g/day. Thirty-seven per cent of patients in the 4 g/day Balsalazide group relapsed compared to 55% of patients in the 2 g/day group (133 patients; RR 0.66; 95% CI 0.45 to 0.97). One study found a statistically significant difference between Salofalk granules 3 g and 1.5 g/day. Twenty-five per cent of patients in the Salofalk 3 g/day group relapsed compared to 39% of patients in the 1.5 g/day group (429 patients; RR 0.65; 95% CI 0.49 to 0.86). Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache, dyspepsia, and nasopharyngitis. There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, 5-ASA and SASP, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulations and 5-ASA dose ranging studies. The trials that compared 5-ASA and SASP may have been biased in favour of SASP because most trials enrolled patients known to be tolerant to SASP which may have minimized SASP-related adverse events. AUTHORS' CONCLUSIONS 5-ASA was superior to placebo for maintenance therapy in ulcerative colitis. However, 5-ASA had a statistically significant therapeutic inferiority relative to SASP. Oral 5-ASA administered once daily is as effective and safe as conventional dosing for maintenance of remission in quiescent ulcerative colitis. There does not appear to be any difference in efficacy or safety between the various formulations of 5-ASA. Patients with extensive ulcerative colitis or with frequent relapses may benefit from a higher dose of maintenance therapy. High dose therapy appears to be as safe as low dose and is not associated with a higher incidence of adverse events.
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Affiliation(s)
- Brian G Feagan
- Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada.
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Choi CH, Kim YH, Kim YS, Ye BD, Lee KM, Lee BI, Jung SA, Kim WH, Lee H. [Guidelines for the management of ulcerative colitis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2012; 59:118-40. [PMID: 22387836 DOI: 10.4166/kjg.2012.59.2.118] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by a relapsing and remitting course. The quality of life can decreases significantly during exacerbations of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies are currently used for the management of UC. However, many challenging issues exist and sometimes these lead to differences in practice between clinicians. Therefore, Inflammatory Bowel Diseases (IBD) Study Group of Korean Association for the Study of Intestinal Diseases (KASID) set out the Korean guidelines for the management of UC. These guidelines are made by the adaptation using several foreign guidelines and encompass treatment of active colitis, maintenance of remission and indication for surgery in UC. The specific recommendations are presented with the quality of evidence. These are the first Korean treatment guidelines for UC and will be revised with new evidences on treatment of UC.
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Affiliation(s)
- Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Korea
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25
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Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis. Am J Gastroenterol 2012; 107:167-76; author reply 177. [PMID: 22108446 DOI: 10.1038/ajg.2011.410] [Citation(s) in RCA: 115] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, no recent meta-analysis has studied the relative efficacies of differing routes of administration. METHODS MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through May 2011). Eligible trials recruited adults with mildly to moderately active UC, or quiescent UC, and compared oral 5-ASAs with either topical 5-ASAs or a combination of oral and topical 5-ASAs. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active UC, and RR of relapse of disease activity in quiescent UC, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. RESULTS The search identified 3,061 citations, and 12 randomized controlled trials (RCTs) were eligible. Four compared topical with oral 5-ASAs in active UC remission, with an RR of no remission with topical 5-ASAs of 0.82 (95% CI=0.52-1.28). Four trials compared combined with oral 5-ASAs in active UC (RR of no remission=0.65; 95% CI=0.47-0.91; NNT=5). Three RCTs compared intermittent topical with oral 5-ASAs in preventing relapse of quiescent UC (RR=0.64; 95% CI=0.43-0.95; NNT=4), and two compared combined with oral 5-ASAs (RR of relapse=0.48; 95% CI=0.17-1.38). CONCLUSIONS Combined 5-ASA therapy appeared superior to oral 5-ASAs for induction of remission of mildly to moderately active UC. Intermittent topical 5-ASAs appeared superior to oral 5-ASAs for preventing relapse of quiescent UC.
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Gisbert JP, Chaparro M, Gomollón F. Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease. World J Gastroenterol 2011; 17:3467-78. [PMID: 21941413 PMCID: PMC3163244 DOI: 10.3748/wjg.v17.i30.3467] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2011] [Revised: 03/29/2011] [Accepted: 04/05/2011] [Indexed: 02/06/2023] Open
Abstract
Misconceptions are common in the care of patients with inflammatory bowel disease (IBD). In this paper, we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines, to review the related scientific evidence, and make appropriate recommendations. Prevention of errors needs knowledge to avoid making such errors through ignorance. However, the amount of knowledge is increasing so quickly that one new danger is an overabundance of information. IBD is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical problems. With regard to the use of 5-aminosalicylates, the best practice may to be consider abandoning the use of these drugs in patients with small bowel Crohn’ s disease. The combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis; once-daily treatment should be offered as a first choice regimen due to its better compliance and higher efficacy. With regard to thiopurines, they seem to be as effective in ulcerative colitis as in Crohn’ s disease. Underdosing of thiopurines is a form of undertreatment. Thiopurines should probably be continued indefinitely because their withdrawal is associated with a high risk of relapse. Mercaptopurine is a safe alternative in patients with digestive intolerance or hepatotoxicity due to azathioprine. Finally, thiopurine methyltransferase (TPMT) screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related.
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27
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Krenzlin S, Siepmann F, Wils D, Guerin-Deremaux L, Flament MP, Siepmann J. Non-coated multiparticulate matrix systems for colon targeting. Drug Dev Ind Pharm 2011; 37:1150-9. [PMID: 21417601 DOI: 10.3109/03639045.2011.562214] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Colon specific drug delivery can significantly improve the efficacy of local treatments of inflammatory bowel diseases. Film coatings containing the starch derivative Nutriose have recently been reported to minimize 5-ASA release in media simulating the upper gastro intestinal tract (GIT), while releasing the drug in a time-controlled manner upon contact with feces from Crohn's Disease and Ulcerative Colitis patients. It was the aim of this study to prepare Nutriose-containing matrix pellets and mini tablets in order to avoid a film coating step. METHODS Highly dosed matrix pellets were prepared by extrusion-spheronization, highly dosed mini tablets by compression. Various types of lipids were added and drug release measured in 0.1 N HCl and phosphate buffer pH 6.8, optionally containing pepsin and pancreatin. RESULTS The type of added lipid and the preparation technique, in particular the curing conditions, significantly affected the resulting drug release kinetics. Glyceryl palmitostearate containing pellets and mini tablets showed the most promising results upon appropriate curing, minimizing premature drug release in media simulating the upper GIT. CONCLUSION The proposed novel multiparticulates do not require a film coating step and show an interesting potential for site-specific drug delivery to the colon of inflammatory bowel disease patients.
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Affiliation(s)
- S Krenzlin
- Université Lille Nord de France, College of Pharmacy, France
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28
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Sonu I, Lin MV, Blonski W, Lichtenstein GR. Clinical pharmacology of 5-ASA compounds in inflammatory bowel disease. Gastroenterol Clin North Am 2010; 39:559-599. [PMID: 20951918 DOI: 10.1016/j.gtc.2010.08.011] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Mesalamine has been the first-line of therapy in patients with inflammatory bowel disease (IBD) since the 1960s. This article serves as a review of the different 5-aminosalicylic acid compounds, release formulations, use and dosing in the treatment of IBD, in particular ulcerative colitis.
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Affiliation(s)
- Irene Sonu
- University of Pennsylvania School of Medicine, Suite 100, Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104, USA
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29
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Cohen RD, Yu AP, Wu EQ, Xie J, Mulani PM, Chao J. Systematic review: the costs of ulcerative colitis in Western countries. Aliment Pharmacol Ther 2010; 31:693-707. [PMID: 20064142 DOI: 10.1111/j.1365-2036.2010.04234.x] [Citation(s) in RCA: 216] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Early onset and complications such as hospitalization and surgery contribute to the economic burden of ulcerative colitis. AIM To review systematically the literature on costs of ulcerative colitis in Western countries. METHODS Studies estimating costs of ulcerative colitis in Western countries were identified using Medline, EMBASE and ISI Web of Science and were rated based on relevance and reliability of estimates. All costs were adjusted to 2008 currency values. A parallel review focused on the impact of disease severity on costs, hospitalizations and surgeries. RESULTS Estimated annual per-patient direct medical costs of ulcerative colitis ranged from $6217 to $11,477 in the United States and from euro8949 to euro10,395 in Europe. Hospitalizations accounted for 41-55% of direct medical costs. Indirect costs accounted for approximately one-third of total costs in the United States and 54-68% in Europe. Total economic burden of ulcerative colitis was estimated at $8.1-14.9 billion annually in the United States and at euro12.5-29.1 billion in Europe; total direct costs were $3.4-8.6 billion in the United States and euro5.4-12.6 billion in Europe. Direct costs, hospitalizations and surgeries increased with worsening disease severity. CONCLUSIONS Ulcerative colitis is a costly disease. Hospitalizations contribute significantly to direct medical costs, and indirect costs are considerable, having previously been substantially underestimated.
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Affiliation(s)
- R D Cohen
- Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, Chicago, IL 60637, USA.
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Ooi CJ, Fock KM, Makharia GK, Goh KL, Ling KL, Hilmi I, Lim WC, Kelvin T, Gibson PR, Gearry RB, Ouyang Q, Sollano J, Manatsathit S, Rerknimitr R, Wei SC, Leung WK, de Silva HJ, Leong RW. The Asia-Pacific consensus on ulcerative colitis. J Gastroenterol Hepatol 2010; 25:453-468. [PMID: 20370724 DOI: 10.1111/j.1440-1746.2010.06241.x] [Citation(s) in RCA: 122] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Inflammatory bowel disease (IBD) is increasing in many parts of the Asia-Pacific region. There is a need to improve the awareness of IBD and develop diagnostic and management recommendations relevant to the region. This evidence-based consensus focuses on the definition, epidemiology and management of ulcerative colitis (UC) in Asia. A multi-disciplinary group developed the consensus statements, reviewed the relevant literature, and voted on them anonymously using the Delphi method. The finalized statements were reviewed to determine the level of consensus, evidence quality and strength of recommendation. Infectious colitis must be excluded prior to diagnosing UC. Typical histology and macroscopic extent of the disease seen in the West is found in the Asia-Pacific region. Ulcerative colitis is increasing in many parts of Asia with gender distribution and age of diagnosis similar to the West. Extra-intestinal manifestations including primary sclerosing cholangitis are rarer than in the West. Clinical stratification of disease severity guides management. In Japan, leukocytapheresis is a treatment option. Access to biologic agents remains limited due to high cost and concern over opportunistic infections. The high endemic rates of hepatitis B virus infection require stringent screening before initiating immune-suppressive agents. Vaccination and prophylactic therapies should be initiated on a case-by-case basis and in accordance with local practice. Colorectal cancer complicates chronic colitis. A recent increase in UC is reported in the Asia-Pacific region. These consensus statements aim to improve the recognition of UC and assist clinicians in its management with particular relevance to the region.
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Affiliation(s)
- Choon Jin Ooi
- Department of Gastroenterology and Hepatology, Duke-NUS Graduate Medical School and Singapore General Hospital, Singapore.
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Pimpo MT, Galletti B, Palumbo G, Viscido A, Gentile P, Caprilli R, Frieri G. Mesalazine vanishing time from rectal mucosa following its topical administration. J Crohns Colitis 2010; 4:102-5. [PMID: 21122491 DOI: 10.1016/j.crohns.2009.08.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2009] [Revised: 08/10/2009] [Accepted: 08/12/2009] [Indexed: 02/08/2023]
Abstract
To investigate how long and how much Mesalazine (M) is available inside the rectal mucosa following its topical instillation, in patients (pts) with Ulcerative Colitis (UC). Two rectal biopsies for M concentration were obtained from 45 UC pts in clinical remission and on oral M treatment (OT), before a 4g enema randomly given to consentient pts every day (Group A, 15 pts), every 2 days (Group B, 15 pts) and every 3 days (Group C, 15 pts). Two additional biopsies were taken 1, 2 and 3 days after the last enema in group A, B and C respectively, at least 10 days later. All biopsies were immediately frozen at -80°C for later assay by means of high-performance light chromatography (HPLC). Data were analyzed using Student's t-test. Mean values±standard deviation of M mucosal concentration (ng/mg of tissue) were 1.32±1.41, 56.1±39.2, 9.65±6.60, and 6.39±5.03 in pts receiving OT alone, groups A, B and C, respectively. Values in Group A were statistically higher (p<0.001) than those in Groups B and C while no differences were found between Groups B and C. Values of OT were lower than groups A, B and C. M mucosal concentration rapidly decreases 2 days after a 4g enema, but after three days is still higher than OT alone. These results may provide data which would be useful to plan topical therapy and improve adherence to treatment.
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Affiliation(s)
- M T Pimpo
- S. Pietro-Fatebenefratelli Hospita, Rome, Italy
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The long journey of salicylates in ulcerative colitis: The past and the future. J Crohns Colitis 2009; 3:149-56. [PMID: 21172263 DOI: 10.1016/j.crohns.2009.05.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2009] [Revised: 05/05/2009] [Accepted: 05/05/2009] [Indexed: 02/08/2023]
Abstract
The advent of salicylates in the treatment of ulcerative colitis started in 1938 with the discovery of Salazopyrin by Nanna Svartz. This drug offered for the first time a therapeutic chance to patients with ulcerative colitis. In this paper we describe the fascinating history of Salazopyrin and salicylates from the first serendipitous observations to the last randomized clinical trials. Attention was paid to the pharmacokinetics and the mechanism of action of 5-aminosalicylates and, in particular, to the issue of the mucosal concentrations of 5-aminosalicylates and its therapeutic efficacy. Moreover a look at the new oral mesalazine formulations that allow the homogenous distribution of 5-aminosalicylate through all the large bowel was taken. Lastly, the possible use of mesalazine in the prevention of colorectal cancer was reviewed.
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Lichtenstein GR, Kamm MA. Review article: 5-aminosalicylate formulations for the treatment of ulcerative colitis--methods of comparing release rates and delivery of 5-aminosalicylate to the colonic mucosa. Aliment Pharmacol Ther 2008; 28:663-73. [PMID: 18532992 DOI: 10.1111/j.1365-2036.2008.03751.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Many oral 5-aminosalicylic acid (5-ASA) formulations are designed to maximize 5-ASA release in the colon where it acts topically on the colonic mucosa. Delayed-release formulations and azo-prodrugs minimize 5-ASA absorption in the upper gastrointestinal (GI) tract. AIMS To review methods for assessing 5-ASA release and colonic distribution from oral formulations, and the potential use of this information for guiding clinical decisions. METHODS PubMed and recent conference abstracts were searched for articles describing techniques used to assess 5-ASA release from ulcerative colitis (UC) therapies. RESULTS In-vitro GI models, although unable to simulate more complex aspects of GI physiology, can provide useful data on 5-ASA release kinetics and bioaccessibility. Gamma-scintigraphy is useful for investigating GI disintegration of different formulations, but may not accurately reflect 5-ASA distribution. Plasma pharmacokinetic studies provide data on systemic exposure, but not on colonic distribution or mucosal uptake. Mucosal biopsies provide direct evidence of colonic distribution and may predict clinical efficacy, but must be interpreted cautiously because of considerable inter-subject variability and other confounding factors. CONCLUSION While assessment of 5-ASA release is important, limitations of individual measurement techniques mean that randomized clinical studies in UC patients remain the best guide for dosing and treatment regimen decisions.
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Affiliation(s)
- G R Lichtenstein
- Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
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Travis SPL, Stange EF, Lémann M, Oresland T, Bemelman WA, Chowers Y, Colombel JF, D'Haens G, Ghosh S, Marteau P, Kruis W, Mortensen NJM, Penninckx F, Gassull M. European evidence-based Consensus on the management of ulcerative colitis: Current management. J Crohns Colitis 2008; 2:24-62. [PMID: 21172195 DOI: 10.1016/j.crohns.2007.11.002] [Citation(s) in RCA: 365] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2007] [Accepted: 11/23/2007] [Indexed: 02/08/2023]
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Gisbert JP, Gomollón F. Errores frecuentes en el manejo del paciente ambulatorio con enfermedad inflamatoria intestinal. GASTROENTEROLOGIA Y HEPATOLOGIA 2007; 30:469-86. [DOI: 10.1157/13110491] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Gandia P, Idier I, Houin G. Is once-daily mesalazine equivalent to the currently used twice-daily regimen? A study performed in 30 healthy volunteers. J Clin Pharmacol 2007; 47:334-42. [PMID: 17322145 DOI: 10.1177/0091270006296522] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
A randomized, 2-way, crossover study was conducted in 30 volunteers to compare the pharmacokinetic profile of a new once-daily dosing regimen of mesalazine (1 x 4 g/d) with the current twice-daily dosage (2 x 2 g/d) used in many European countries. The 2 dosages were administrated orally for 8 days, separated by a 2-week washout. Plasma concentrations of mesalazine and N-acetyl-mesalazine were determined on days 1 and 8 by a validated high-performance liquid chromatography method and C(max), t(max), and AUCs calculated. The bioequivalence was obtained for a 90% confidence interval of the AUC(0-24h) ratio (test/reference) for mesalazine and N-acetyl-mesalazine on days 1 and 8, within the range of 0.80 to 1.25. The bioequivalence was demonstrated on day 1 for mesalazine and N-acetyl-mesalazine and on day 8 for mesalazine. As it is desirable to offer patients a preparation with a less frequent administration to enhance compliance, this once-daily regimen may be an attractive dosing option.
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Affiliation(s)
- Peggy Gandia
- Laboratoire de Pharmacocinétique et Toxicologie Clinique, Institut Fédératif de Biologie, Hôpital Purpan, TSA 70034, 330 avenue de Grande Bretagne, 31059 Toulouse cedex 9, France
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Lakatos L, Lakatos PL. [Medical therapy of inflammatory bowel diseases: ulcerative colitis]. Orv Hetil 2007; 148:1163-1170. [PMID: 17573252 DOI: 10.1556/oh.2007.28063] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
There are fewer significant changes in the medical therapy of ulcerative colitis (UC) compared to Crohn's disease. The most important factors that determine therapy are disease extent and severity. 5-aminosalicylates (5-ASA) constitute the treatment of choice in mild-to-moderate UC. The efficacy of new compounds (e.g. mesalazine) is only mildly improved compared to sulphasalazine; however, their use has become more frequent due to a more favorable side effects profile. Topical medication is more effective in proctitis and distal colitis, and the combination of topical and orally-administered drugs is superior to oral therapy alone also in extensive disease. Thus, this latter regimen should be considered for cases where the escalation of treatment is required. Systemic steroids still represent the first line therapy in acute, severe UC, while in patients who do not respond to steroids, cyclosporine and infliximab should be considered as a second line therapy and as alternatives for colectomy. Maintenance treatment is indicated in all UC cases. 5-ASA compounds are suggested as first line maintenance therapy with the optimal dose still being under investigation. Topical compounds are effective also for maintenance in distal colitis or proctitis, if accepted by the patients. Immunosuppressives, especially azathioprine, should be considered in chronically active, steroid dependent or resistant patients. According to recent publications, azathioprine is almost equally effective in UC and CD. The question of chemoprevention is important during maintenance. There are increasing data supporting the notion that aminosalicylates may lower the risk for UC-associated colorectal cancer. The most important changes in the management of UC are the more frequent use of topical aminosalicylates and azathioprine, the availability of infliximab in severe UC, and increasing use of aminosalicylates for chemoprevention of colorectal carcinoma. Furthermore, adequate attention is needed to better organize the patient-doctor relationship and for greater adherence to medical therapy.
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Affiliation(s)
- László Lakatos
- Csolnoky Ferenc Megyei Kórház I. Belgyógyászati Osztály Veszprém.
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Banks C, Forbes A. Topical treatment of ulcerative colitis. Some reflections. Dig Liver Dis 2007; 39:338-41. [PMID: 17317345 DOI: 10.1016/j.dld.2006.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2006] [Accepted: 11/03/2006] [Indexed: 12/11/2022]
Affiliation(s)
- C Banks
- Centre for Gastroenterology, University College London, UK
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Creed TJ, Probert CSJ. Review article: steroid resistance in inflammatory bowel disease - mechanisms and therapeutic strategies. Aliment Pharmacol Ther 2007; 25:111-22. [PMID: 17229236 DOI: 10.1111/j.1365-2036.2006.03156.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Steroid resistance in inflammatory bowel disease presents a difficult clinical challenge. The advent of biological therapies coupled with an increasing understanding of the pathogenesis of inflammatory bowel disease has provided new therapeutic options. METHODS We review the available literature of the mechanisms behind steroid resistance. In addition, we outline some of the options available for treating those patients who fail to respond adequately to glucocorticoids. RESULTS Approximately 30% of patients prescribed glucocorticoids will not achieve clinical remission. Many such patients are offered immunosuppressive or, recently, biological agents. However, these agents are ineffective in a large proportion of patients. Immunosuppressive agents only bring 40-60% of patients into remission, and biological agents typically induce remission in just 40% of patients. In this review, the possible explanations for glucocorticoid resistance are discussed. Recent evidence suggests that in many patients it is mediated by interleukin-2. Basiliximab, a biological agent that interrupts interleukin-2 signalling, has shown significant benefit in early clinical studies. CONCLUSIONS Patients who fail to respond to steroid therapy should have alternative agents introduced in a timely fashion. Steroid refractory inflammatory bowel disease remains a difficult condition to treat, but new therapies and managements are emerging.
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Affiliation(s)
- T J Creed
- University Research Centre for Neuroendocrinology, Bristol Royal Infirmary, Bristol, UK.
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Gionchetti P, Rizzello F, Morselli C, Tambasco R, Campieri M. Review article: aminosalicylates for distal colitis. Aliment Pharmacol Ther 2006; 24 Suppl 3:41-4. [PMID: 16961744 DOI: 10.1111/j.1365-2036.2006.03059.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
About two-thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure and therefore may be effectively treated with topical treatment. This allows the delivery of the active drug directly to the site of inflammation, limiting the systemic absorption and the potential side effects. Topical aminosalicylate therapy is the most effective approach, provided that the formulation reaches the upper extent of the disease. Suppositories should be considered the treatment of choice for proctitis and distal sigmoiditis. A 1 g Pentasa-suppository once daily induces a quicker clinical and endoscopic remission and was better tolerated than a 500-mg suppository twice daily. Enemas, foams and gel, thanks to their proximal spread, should be the treatment of choice for proctosigmoiditis and left-sided colitis. Oral aminosalicylates are less effective than topical therapies for patients with active disease; however, a combination of oral and topical aminosalicylates can be successfully tried in refractory patients. Topical aminosalicylates also play an important role in the maintenance of remission, and the combination of oral plus rectal 5-aminosalicylate is superior to the single agent. Patients who prefer not to continue on long-term rectal therapy can be treated with oral aminosalicylates.
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Affiliation(s)
- P Gionchetti
- Department of Internal Medicine, University of Bologna, Bologna, Italy.
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D'Haens G, Hommes D, Engels L, Baert F, van der Waaij L, Connor P, Ramage J, Dewit O, Palmen M, Stephenson D, Joseph R. Once daily MMX mesalazine for the treatment of mild-to-moderate ulcerative colitis: a phase II, dose-ranging study. Aliment Pharmacol Ther 2006; 24:1087-97. [PMID: 16984503 DOI: 10.1111/j.1365-2036.2006.03082.x] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND SPD476 (MMX mesalazine), is a novel, once daily, high-strength mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System (MMX) technology to delay and extend delivery of the active drug throughout the colon. AIM To assess the safety and efficacy of MMX mesalazine in patients with mild-to-moderately active ulcerative colitis, in a pilot, phase II, randomized, multicentre, double-blind, parallel-group, dose-ranging study (SPD476-202). METHODS Thirty-eight patients with mild-to-moderately active ulcerative colitis were randomized to MMX mesalazine 1.2, 2.4 or 4.8 g/day given once daily for 8 weeks. Remission ulcerative colitis-disease activity index (UC-DAI) < or =1, a score of 0 for rectal bleeding and stool frequency, and > or =1 -point reduction in sigmoidoscopy score from baseline was the primary end point. RESULTS Week 8 remission rates were 0%, 31% and 18% of patients receiving MMX mesalazine 1.2, 2.4 and 4.8 g/day respectively. No statistically significant difference in remission was observed between treatment groups. MMX mesalazine 2.4 and 4.8 g/day groups demonstrated greater improvement in overall UC-DAI and component scores from baseline, compared with the 1.2 g/day group. CONCLUSION MMX mesalazine given as 2.4 or 4.8 g/day once daily is well tolerated and effective for the treatment of mild-to-moderately active ulcerative colitis.
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Affiliation(s)
- G D'Haens
- Department of Gastroenterology, Imelda General Hospital, Imelda GI Clinical Research Center, Imeldalaan, Bonheiden, Belgium.
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Orchard T, Probert CS, Keshav S. Review article: maintenance therapy in patients with ulcerative colitis. Aliment Pharmacol Ther 2006; 24 Suppl 1:17-22. [PMID: 16939425 DOI: 10.1111/j.1365-2036.2006.03071.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
British Society of Gastroenterology guidelines recommend that all patients with ulcerative colitis should receive long-term therapy with a 5-aminosalicylic acid compound to maintain remission. Recent studies have shown that time spent in remission is longer when the maintenance dose is increased from 1.2 to 2.4 g/day, with patients with extensive disease benefiting most from an increase with dosage. A retrospective analysis also found that the frequency of relapse was lower in patients taking more than the median dose of 5-aminosalicylic acid (1.6 g/day) compared with those taking less than the median dose. Similarly, when 5-aminosalicylic acids are used to induce remission, continuing the induction dosage for an extra 4 weeks prolongs remission and reduces the frequency of relapse. However, patients rarely comply fully with the prescribed dose regimen, which can lead to effective under-dosing. The recent discovery that 5-aminosalicylic acids may act in ulcerative colitis by activating peroxisome proliferator-activated receptor-gamma, a nuclear receptor that plays a role in the control of cell proliferation and apoptosis, has given new impetus to the idea that long-term therapy with 5-aminosalicylic acid may reduce the risk of colorectal cancer. Epidemiological studies are beginning to provide evidence to support this view. Accumulating evidence suggests that the next revision of the clinical guidelines should suggest life-long doses of 5-aminosalicylic acid of > or =2 g/day for maintenance of remission in patients with ulcerative colitis.
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Affiliation(s)
- T Orchard
- St Mary's Hospital & Imperial College, London, UK.
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43
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Affiliation(s)
- A Nilsson
- Department of Medicine, University of Lund, Lund, Sweden.
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Travis SPL. New thinking: theory vs practice. A case study illustrating evidence-based therapeutic decision making. Colorectal Dis 2006; 8 Suppl 1:25-9. [PMID: 16594961 DOI: 10.1111/j.1463-1318.2006.00989.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Evidence-based medicine (EBM) plays a key role for decision making in clinical practice. Clinicians are encouraged to adhere to treatment guidelines based on high quality clinical trials, systematic reviews and meta-analyses, that are the focus of the Cochrane Collaboration. EBM is not, however, a panacea for medical decision making. The results of randomized clinical trials apply to populations of patients, and the challenge is to translate the results to individuals. Individual patients require different thought processes because presentation and response vary, and external factors (e.g. patient preference) influence the choice of treatment. The application of EBM demands clinical judgement. The case of a 28 year old scientist who presented with typical features of moderate ulcerative colitis, illustrates the dilemma. At each stage of his illness the treatment options based on EBM were discussed, including high dose 5-aminosalicyclic acid with or without topical therapy, corticosteroids, infliximab, immunomodulation, complementary therapy and surgery. Ultimately, therapeutic decisions depended on the patient's circumstances, preferences and response. Decisions should avoid circular motion caused by the illusion of progress and always consider the direction of travel.
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Affiliation(s)
- S P L Travis
- John Radcliffe Hospital and Linacre College, Oxford, UK.
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Travis S. Advances in therapeutic approaches to ulcerative colitis and Crohn's disease. Curr Gastroenterol Rep 2006; 7:475-84. [PMID: 16313878 DOI: 10.1007/s11894-005-0079-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Advances (from 2004 to 2006) in the use of conventional agents include the molecular mechanisms of action, which have implications for monitoring (azathioprine and thioguanosine triphosphate) and chemoprevention (mesalamine and peroxisome proliferator activated receptor gamma). Advances in biotherapy include new data on monoclonal antibodies (infliximab in ulcerative colitis, adalimumab, certolizumab pegol, fontolizumab, selective anti-adhesion molecules, and others), antisense oligonucleotides, the development of small molecules, and cell-gene therapy (including helminth ova, leukocytapheresis, stem cell transplantation, and probiotic intestinal mucosal delivery systems). However, management of inflammatory bowel disease is about more than drug therapy, dose, and timing. The goals remain induction of remission, limitation of side effects, modification of the pattern of disease, and avoidance of complications. With the cost and complexity of biotherapy, inflammatory bowel disease is emerging as a specific subspecialty.
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Affiliation(s)
- Simon Travis
- Gastroenterology Unit, John Radcliffe Hospital, Oxford OX3 9DU, UK.
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Travis S. What is the optimal dosage of mesalazine to maintain remission in patients with ulcerative colitis? ACTA ACUST UNITED AC 2005; 2:564-5. [PMID: 16327832 DOI: 10.1038/ncpgasthep0336] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2005] [Accepted: 09/27/2005] [Indexed: 12/18/2022]
Affiliation(s)
- Simon Travis
- Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
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47
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Affiliation(s)
- S P L Travis
- John Radcliffe Hospital and Linacre College, Old Road, Headington, Oxford OX3 7LJ, UK.
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