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Improda N, Chioma L, Capalbo D, Bizzarri C, Salerno M. Glucocorticoid treatment and adrenal suppression in children: current view and open issues. J Endocrinol Invest 2025; 48:37-52. [PMID: 39352628 PMCID: PMC11729088 DOI: 10.1007/s40618-024-02461-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 08/23/2024] [Indexed: 01/03/2025]
Abstract
PURPOSE Glucocorticoids (GCs) are commonly used for several acute and chronic pediatric diseases. However, chronic treatment may result in hypothalamic-pituitary-adrenal axis (HPA) dysfunction. Glucocorticoid-induced adrenal insufficiency (GI-AI) is indeed the most frequent cause of adrenal insufficiency (AI) in children, possibly resulting in a life-threatening event such as adrenal crisis (AC). It is generally underestimated, especially when using non-systemic glucocorticoid formulations. This review aims at summarizing current evidence on the effects of long-term GC treatment on the HPA axis, management of GC tapering and assessment of the HPA recovery. METHODS We conducted a narrative review of the relevant literature focusing on pathogenic mechanisms, predictive factors, diagnosis and treatment of GI-AI. RESULTS All types of GCs, whatever the route of administration, may have suppressive effects on the HPA axis, especially when compounds with higher potency and long half-life are used. Moreover, chronic GC administration is the most common cause of Cushing syndrome in children. In order to overcome the risk of GI-AI, slow withdrawal of GCs is necessary. When approaching the replacement dose, it is recommended to switch to shorter half-life formulations such as hydrocortisone. Assessment of HPA axis recovery with basal and stimulated cortisol levels may help detecting children at risk of AC that may require hydrocortisone supplementation. CONCLUSION The management of GI-AI in children is challenging and many areas of uncertainty remain. Improving the knowledge on long-term GC effects on HPA in children, the management of steroid discontinuation and emergency dosing may help preventing GI-AI symptoms and acute hospital admission for AC.
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Affiliation(s)
- Nicola Improda
- Neuro-Endocrine Diseases and Obesity Unit, Department of Neurosciences, Santobono- Pausilipon Children's Hospital, Napoli, Italy
| | - Laura Chioma
- Endocrinology Unit, University Hospital Pediatric Department, Bambino Gesù Children's Hospital, Rome, Italy
| | - Donatella Capalbo
- Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Endo-ERN Center for Rare Endocrine Conditions, Naples, Italy
| | - Carla Bizzarri
- Endocrinology Unit, University Hospital Pediatric Department, Bambino Gesù Children's Hospital, Rome, Italy
| | - Mariacarolina Salerno
- Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Endo-ERN Center for Rare Endocrine Conditions, Naples, Italy.
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Resál T, Mangó K, Bacsur P, Szántó K, Pigniczki D, Keresztes C, Rutka M, Bálint A, Milassin Á, Bor R, Fábián A, Szepes Z, Farkas K, Monostory K, Molnár T. Possible genetical predictors of efficacy and safety of budesonide-MMX in patients with mild-to-moderate ulcerative colitis, and safety comparison with methylprednisolone. Expert Opin Drug Saf 2023; 22:517-524. [PMID: 36811412 DOI: 10.1080/14740338.2023.2181336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 01/23/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND Budesonide-MMX is a topically active corticosteroid degraded by cytochrome-P450 enzymes, resulting in favorable side-effect profile. We aimed to assess the effect of CYP genotypes on safety and efficacy, and make a direct comparison with systemic corticosteroids. RESEARCH DESIGN AND METHODS We enrolled UC patients receiving budesonide-MMX and IBD patients on methylprednisolone in our prospective, observational-cohort study. Before and after treatment regimen clinical activity indexes, laboratory parameters (electrolytes, CRP, cholesterol, triglyceride, dehydroepiandrosterone, cortisol, beta-crosslaps, osteocalcin), and body composition measurements were assessed. CYP3A4 and CYP3A5 genotypes were determined in the budesonide-MMX group. RESULTS 71 participants were enrolled (budesonide-MMX: 52; methylprednisolone: 19). CAI decreased (p<0.05) in both groups. Cortisol decreased (p<0.001), and the level of cholesterol was elevated in both groups (p<0.001). Body composition altered only following methylprednisolone. Bone homeostasis (osteocalcin; p<0.05) and DHEA (p<0.001) changed more prominently after methylprednisolone. Glucocorticoid-related adverse events were more common following methylprednisolone treatment (47.4% compared to 1.9%). CYP3A5(*1/*3) genotype positively influenced efficacy, but not safety. Only one patient's CYP3A4 genotype differed. CONCLUSIONS CYP genotypes can affect the efficacy of budesonide-MMX; however, further studies would be needed with analyses of gene expression. Although budesonide-MMX is safer than methylprednisolone, due to glucocorticoid-related side effects, admission should require greater precaution.
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Affiliation(s)
- Tamás Resál
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Katalin Mangó
- Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
| | - Péter Bacsur
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Kata Szántó
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Daniella Pigniczki
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- Department of Surgery, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Csilla Keresztes
- Department for Medical Communication and Translation Studies, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Mariann Rutka
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Anita Bálint
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Ágnes Milassin
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Renáta Bor
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Anna Fábián
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Zoltán Szepes
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Klaudia Farkas
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Katalin Monostory
- Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
| | - Tamás Molnár
- Gastroenterology, Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
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Study on the regulatory effect of herbal cake-partitioned moxibustion on colonic CD206, AMPK and TSC2 in rats with Crohn disease. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE 2021. [DOI: 10.1007/s11726-021-1263-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Nakase H, Uchino M, Shinzaki S, Matsuura M, Matsuoka K, Kobayashi T, Saruta M, Hirai F, Hata K, Hiraoka S, Esaki M, Sugimoto K, Fuji T, Watanabe K, Nakamura S, Inoue N, Itoh T, Naganuma M, Hisamatsu T, Watanabe M, Miwa H, Enomoto N, Shimosegawa T, Koike K. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J Gastroenterol 2021; 56:489-526. [PMID: 33885977 PMCID: PMC8137635 DOI: 10.1007/s00535-021-01784-1] [Citation(s) in RCA: 251] [Impact Index Per Article: 62.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn's disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.
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Affiliation(s)
- Hiroshi Nakase
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan ,grid.263171.00000 0001 0691 0855Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuoku, Sapporo, Hokkaido 060-8543 Japan
| | - Motoi Uchino
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Shinichiro Shinzaki
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Minoru Matsuura
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Katsuyoshi Matsuoka
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Taku Kobayashi
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Masayuki Saruta
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Fumihito Hirai
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Keisuke Hata
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Sakiko Hiraoka
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Motohiro Esaki
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Ken Sugimoto
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Toshimitsu Fuji
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Kenji Watanabe
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Shiro Nakamura
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Nagamu Inoue
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Toshiyuki Itoh
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Makoto Naganuma
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Tadakazu Hisamatsu
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Mamoru Watanabe
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
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Editorial A. CROHN'S DISEASE. CLINICAL RECOMMENDATIONS (PRELIMINARY VERSION). KOLOPROKTOLOGIA 2020; 19:8-38. [DOI: 10.33878/2073-7556-2020-19-2-8-38] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
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6
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Falloon K, Lazarev M. A Primer on IBD: Phenotypes, Diagnosis, Treatment, and Clinical Challenges. MOLECULAR GENETICS OF INFLAMMATORY BOWEL DISEASE 2019:3-24. [DOI: 10.1007/978-3-030-28703-0_1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kuenzig ME, Rezaie A, Kaplan GG, Otley AR, Steinhart AH, Griffiths AM, Benchimol EI, Seow CH. Budesonide for the Induction and Maintenance of Remission in Crohn's Disease: Systematic Review and Meta-Analysis for the Cochrane Collaboration. J Can Assoc Gastroenterol 2018; 1:159-173. [PMID: 30656288 PMCID: PMC6328928 DOI: 10.1093/jcag/gwy018] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Budesonide is an oral glucocorticoid designed for the treatment of inflammatory bowel disease (IBD) that may reduce systemic adverse events (AEs). This review examined the efficacy and safety of budesonide for the induction and maintenance of clinical remission in Crohn’s disease (CD). Methods MEDLINE, EMBASE, other electronic databases, reference lists and conference proceedings were searched to November 2017 to identify randomized controlled trials of budesonide. Outcomes were the induction and maintenance of remission at eight weeks and one year, respectively, as well as corticosteroid-related AEs and abnormal adrenocorticotropic hormone (ACTH) tests. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random effects models. Results Thirteen induction and 10 maintenance trials were included. Budesonide 9 mg/day was more effective than placebo (RR 1.93; 95% CI, 1.37–2.73; GRADE: moderate) but less effective than conventional steroids (RR 0.85; 95% CI, 0.75–0.97; GRADE: moderate) to induce remission. Corticosteroid-related AEs occurred less often with induction doses of budesonide than steroids (RR 0.64; 95% CI, 0.54–0.76; GRADE: moderate); budesonide did not increase AEs relative to placebo (RR 0.97; 95% CI, 0.76–1.23; GRADE: moderate). Budesonide 6 mg/day was not different from placebo for maintaining remission (RR 1.13; 95% CI, 0.94–1.35; GRADE: moderate). Both induction (GRADE: low for 3 mg/day, moderate for 9 mg/day) and maintenance budesonide treatment (GRADE: very low for 3 mg/day, low for 6 mg/day) increased the risk of an abnormal ACTH test compared with placebo, but less than conventional steroids (GRADE: very low for both induction and maintenance). Conclusion For induction of clinical remission, budesonide was more effective than placebo, but less effective than conventional steroids. Budesonide was not effective for the maintenance of remission. Budesonide was safer than conventional steroids, but the long-term effects on the adrenal axis and bone health remain unknown.
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Affiliation(s)
- M Ellen Kuenzig
- CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology Hepatology & Nutrition, Children’s Hospital of Eastern Ontario, Ontario, Ottawa, Canada
| | - Ali Rezaie
- Department of Medicine, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Gilaad G Kaplan
- Department of Medicine, University of Calgary, Calgary, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Canada
| | - Anthony R Otley
- Division of Gastroenterology, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada
| | - A Hillary Steinhart
- Department of Medicine, Division of Gastroenterology, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Anne Marie Griffiths
- Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Eric I Benchimol
- CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology Hepatology & Nutrition, Children’s Hospital of Eastern Ontario, Ontario, Ottawa, Canada
- Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Cynthia H Seow
- Department of Medicine, University of Calgary, Calgary, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Canada
- Correspondence: Cynthia H. Seow, 3280 Hospital Drive NW, TRW building, Rm 6D18, Calgary, AB, T2N 4Z6, Canada, e-mail
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8
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Bezzio C, Festa S, Zerboni G, Papi C, Manes G, Saibeni S. A safety evaluation of budesonide MMX for the treatment of ulcerative colitis. Expert Opin Drug Saf 2018; 17:437-444. [DOI: 10.1080/14740338.2018.1442432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Cristina Bezzio
- Gastroenterology Unit, Rho Hospital, ASST Rhodense, Garbagnate Milanese, Italy
| | | | | | - Claudio Papi
- IBD Unit, San Filippo Neri Hospital, Rome, Italy
| | - Gianpiero Manes
- Gastroenterology Unit, Rho Hospital, ASST Rhodense, Garbagnate Milanese, Italy
| | - Simone Saibeni
- Gastroenterology Unit, Rho Hospital, ASST Rhodense, Garbagnate Milanese, Italy
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Abstract
Inflammatory bowel disease (IBD) includes 2 chronic idiopathic inflammatory diseases: ulcerative colitis and Crohn disease. The incidence and prevalence of IBD is increasing worldwide. It can affect people of all ages, including children and geriatric populations, and can impact all aspects of life. In this article, diagnosis and treatment of IBD in adults, pediatric, pregnant, and elderly populations are explored from the perspective of a primary care physician.
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Affiliation(s)
- Tomoko Sairenji
- Department of Family Medicine, University of Washington, 1959 Northeast Pacific Street E-304, Seattle, WA 98195-6390, USA.
| | - Kimberly L Collins
- Department of Family Medicine, University of Washington, 331 NE Thornton Place, Seattle, WA 98125, USA
| | - David V Evans
- Department of Family Medicine, University of Washington, 1959 Northeast Pacific Street E-304, Seattle, WA 98195-6390, USA
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Park JJ, Yang SK, Ye BD, Kim JW, Park DI, Yoon H, Im JP, Lee KM, Yoon SN, Lee H. Second Korean guidelines for the management of Crohn's disease. Intest Res 2017; 15:38-67. [PMID: 28239314 PMCID: PMC5323307 DOI: 10.5217/ir.2017.15.1.38] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 01/15/2017] [Accepted: 01/16/2017] [Indexed: 02/07/2023] Open
Abstract
Crohn's disease (CD) is a chronic, progressive, and disabling inflammatory bowel disease (IBD) with an uncertain etiopathogenesis. CD can involve any site of the gastrointestinal tract from the mouth to the anus, and is associated with serious complications, such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower compared with those in Western countries, but they have been rapidly increasing during the recent decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies have been applied for the treatment of this disease. Concerning CD management, there have been substantial discrepancies among clinicians according to their personal experience and preference. To suggest recommendable approaches to the diverse problems of CD and to minimize the variations in treatment among physicians, guidelines for the management of CD were first published in 2012 by the IBD Study Group of the Korean Association for the Study of Intestinal Diseases. These are the revised guidelines based on updated evidence, accumulated since 2012. These guidelines were developed by using mainly adaptation methods, and encompass induction and maintenance treatment of CD, treatment based on disease location, treatment of CD complications, including stricture and fistula, surgical treatment, and prevention of postoperative recurrence. These are the second Korean guidelines for the management of CD and will be continuously revised as new evidence is collected.
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Affiliation(s)
- Jae Jun Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Wook Kim
- Department of Internal Medicine, Inje University College of Medicine Ilsan Paik Hospital, Goyang, Korea
| | - Dong Il Park
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jong Pil Im
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kang Moon Lee
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Suwon, Korea
| | - Sang Nam Yoon
- Department of Surgery, Hallym University College of Medicine, Chuncheon, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
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11
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Novaković A. Modern therapy for inflammatory bowel disease. ARHIV ZA FARMACIJU 2017. [DOI: 10.5937/arhfarm1702112n] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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12
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Taylor K, Gibson PR. Conventional Therapy of Ulcerative Colitis: Corticosteroids. CROHN'S DISEASE AND ULCERATIVE COLITIS 2017:399-412. [DOI: 10.1007/978-3-319-33703-6_39] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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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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Ooi CJ, Makharia GK, Hilmi I, Gibson PR, Fock KM, Ahuja V, Ling KL, Lim WC, Thia KT, Wei SC, Leung WK, Koh PK, Gearry RB, Goh KL, Ouyang Q, Sollano J, Manatsathit S, de Silva HJ, Rerknimitr R, Pisespongsa P, Abu Hassan MR, Sung J, Hibi T, Boey CCM, Moran N, Leong RWL. Asia-Pacific consensus statements on Crohn's disease. Part 2: Management. J Gastroenterol Hepatol 2016; 31:56-68. [PMID: 25819311 DOI: 10.1111/jgh.12958] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/11/2015] [Indexed: 02/05/2023]
Abstract
The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology (APAGE) with the goal of developing best management practices, coordinating research and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis (UC) with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis and management of Crohn's disease (CD). The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses and treatment availability. It does not intend to be all-comprehensive and future revisions are likely to be required in this ever-changing field.
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Affiliation(s)
- Choon Jin Ooi
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ida Hilmi
- Division of Gastroenterology and Hepatology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Peter R Gibson
- Monash University Department of Medicine, Box Hill Hospital, Melbourne, Victoria, Australia
| | - Kwong Ming Fock
- Department of Gastroenterology, Changi General Hospital, Singapore
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Khoon Lin Ling
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Wee Chian Lim
- Department of Gastroenterology, Tan Tock Seng Hospital, Singapore
| | - Kelvin T Thia
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Shu-chen Wei
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
| | | | - Poh Koon Koh
- Department of Colorectal Surgery, Singapore General Hospital, Singapore
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Khean Lee Goh
- Division of Gastroenterology and Hepatology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Qin Ouyang
- Division of Gastroenterology, Department of Internal Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Sathaporn Manatsathit
- Department of Medicine, Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - H Janaka de Silva
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Pises Pisespongsa
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Joseph Sung
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | | | | | - Neil Moran
- Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia
| | - Rupert W L Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia
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Abstract
Crohn's disease is increasing in prevalence worldwide. It arises from a complex interplay between both genetic predisposition and environmental influence. A search of databases and clinical practice guidelines was performed to provide the most up-to-date evidence-based approach for diagnosing and managing patients with Crohn's disease. No single gold standard investigation exists. Whilst full ileocolonoscopy with biopsies remains the mainstay for diagnosis, other less invasive imaging modalities are being actively considered in the workup, as well as the use of serological markers. Management should incorporate dietary and lifestyle modifications where necessary, the use of medications in induction and remission of disease, and consideration of surgical intervention where medical therapy has failed.
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Affiliation(s)
- Francis Ha
- Faculty of Medicine, Nursing and Health Science, Monash University, Australia
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Naeem M, Cao J, Choi M, Kim WS, Moon HR, Lee BL, Kim MS, Jung Y, Yoo JW. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles. Int J Nanomedicine 2015. [PMID: 26213469 PMCID: PMC4509535 DOI: 10.2147/ijn.s87816] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy.
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Affiliation(s)
- Muhammad Naeem
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Jiafu Cao
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Moonjeong Choi
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Woo Seong Kim
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Hyung Ryong Moon
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Bok Luel Lee
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Min-Soo Kim
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Yunjin Jung
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Jin-Wook Yoo
- College of Pharmacy, Pusan National University, Busan, South Korea
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López-Serrano P, Briongos EDLF, Alonso EC, Pérez-Calle JL, Rodríguez CF. Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis, with a special focus on corticosteroid therapy. World J Hepatol 2015; 7:539-547. [PMID: 25848477 PMCID: PMC4381176 DOI: 10.4254/wjh.v7.i3.539] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/07/2014] [Accepted: 01/12/2015] [Indexed: 02/06/2023] Open
Abstract
Currently immunosuppressive and biological agents are used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to pre-emptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.
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Murphy PD, Papettas T. Surgical Management of Crohn’s Disease. CROHN'S DISEASE 2015:143-161. [DOI: 10.1007/978-3-319-01913-0_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Corticosteroids are still the mainstay for treating relapses of Crohn’s disease, but should not be used for maintenance therapy. DRUGS & THERAPY PERSPECTIVES 2014. [DOI: 10.1007/s40267-014-0146-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Dignass A, Stoynov S, Dorofeyev AE, Grigorieva GA, Tomsová E, Altorjay I, Tuculanu D, Bunganič I, Pokrotnieks J, Kupčinskas L, Dilger K, Greinwald R, Mueller R. Once versus three times daily dosing of oral budesonide for active Crohn's disease: a double-blind, double-dummy, randomised trial. J Crohns Colitis 2014; 8:970-980. [PMID: 24534142 DOI: 10.1016/j.crohns.2014.01.021] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Revised: 01/27/2014] [Accepted: 01/27/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy. METHODS An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward). RESULTS The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. CONCLUSIONS Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease.
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Affiliation(s)
- Axel Dignass
- Agaplesion Markus Krankenhaus, 1st Dept. of Medicine, Goethe-University, 60431 Frankfurt am Main, Germany.
| | - Simeon Stoynov
- University General Hospital for Active Treatment "Tzaritza Yoanna", Clinic of Gastroenterology, 1527 Sofia, Bulgaria.
| | - Andrey E Dorofeyev
- Donetsk City Clinical Hospital No. 3, Gastroenterology Dept., M. Gorkyy Donetsk National Medical University, Donetsk, 83003 Donetsk, Ukraine.
| | - Galina A Grigorieva
- I.M. Sechenov First Moscow Medical State University, Conservative Coloproctology Dept., 119992 Moscow, Russia
| | - Eva Tomsová
- District Hospital Mladá Boleslav, 293 01 Mladá Boleslav II, Czech Republic.
| | - István Altorjay
- DEOEC, II. sz. Belgyógyászati Klinika, 4012 Debrecen, Hungary.
| | | | - Ivan Bunganič
- Gastro I. s.r.o., Gastroenterology Dept., 080 01 Prešov, Slovakia.
| | - Juris Pokrotnieks
- Paula Stradina University Hospital, Center of Gastroenterology, 1002 Riga, Latvia.
| | - Limas Kupčinskas
- Lithuanian University of Health Sciences, Dept. of Gastroenterology, 50009 Kaunas, Lithuania.
| | - Karin Dilger
- Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany.
| | - Roland Greinwald
- Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany.
| | - Ralph Mueller
- Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany.
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Kuenzig ME, Rezaie A, Seow CH, Otley AR, Steinhart AH, Griffiths AM, Kaplan GG, Benchimol EI. Budesonide for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2014; 2014:CD002913. [PMID: 25141071 PMCID: PMC7133546 DOI: 10.1002/14651858.cd002913.pub3] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Corticosteroids are effective for induction, but not maintenance of remission in Crohn's disease. Significant concerns exist regarding the risk for adverse events, particularly when corticosteroids are used for long treatment courses. Budesonide is a glucocorticoid with limited systemic bioavailability due to extensive first-pass hepatic metabolism and is effective for induction of remission in Crohn's disease. OBJECTIVES To evaluate the efficacy and safety of oral budesonide for maintenance of remission in Crohn's disease. SEARCH METHODS The following databases were searched from inception to 12 June 2014: PubMed, MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched. SELECTION CRITERIA Randomized controlled trials comparing budesonide to a control treatment, or comparing two doses of budesonide, were included. The study population included patients of any age with quiescent Crohn's disease. DATA COLLECTION AND ANALYSIS Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was maintenance of remission at various reported follow-up times during the study. Secondary outcomes included: time to relapse, mean change in CDAI, clinical, histological, improvement in quality of life, adverse events and study withdrawal. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference (MD) and 95% CI for continuous outcomes. Data were analysed on an intention-to-treat basis. The Chi(2) and I(2) statistics were used to assess heterogeneity. Random-effects models were used to allow for expected clinical and statistical heterogeneity. The overall quality of the evidence supporting the primary outcome was assessed using the GRADE criteria. MAIN RESULTS Twelve studies (n = 1273 patients) were included in the review: eight studies compared budesonide to placebo, one compared budesonide to 5-aminosalicylates, one compared budesonide to traditional systemic corticosteroids, one compared budesonide to azathioprine, and one compared two doses of budesonide. Nine studies used a controlled ileal release form of budesonide, while three used a pH-modified release formulation. Nine studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to blinding and one of these studies also had inadequate allocation concealment. Budesonide 6 mg daily was no more effective than placebo for maintenance of remission at 3 months, 6 months or 12 months. At three months 64% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.25, 95% CI 1.00 to 1.58; 6 studies, 540 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to moderate heterogeneity (I(2) = 56%) and sparse data (315 events). At six months 61% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.15, 95% CI 0.95 to 1.39; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (238 events). At 12 months 55% of budesonide 6 mg patients remained in remission compared to 48% of placebo patients (RR 1.13; 95% CI 0.94 to 1.35; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (215 events). Similarly, there was no significant benefit for budesonide 3 mg compared to placebo at 6 and 12 months. There was no statistically significant difference in continued remission at 12 months between budesonide and weaning doses of prednisolone (RR 0.79; 95% CI 0.55 to 1.13; 1 study, 90 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (51 events) and high risk of bias (no blinding). Budesonide 6 mg was better than mesalamine 3 g/day at 12 months (RR 2.51, 95% CI 1.03 to 6.12; 1 study, 57 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (18 events) and high risk of bias (no blinding). There was no statistically significant difference in continued remission at 12 months between budesonide and azathioprine (RR 0.81; 95% CI 0.61 to 1.08; 1 study 77 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to sparse data (55 events) and high risk of bias (single-blind and no allocation concealment). The use of budesonide 6 mg resulted in slight improvements in CDAI scores when assessed at 6 months (MD -24.30, 95% CI -46.31 to -2.29) and 12 months (MD -23.49, 95% CI -46.65 to -0.32) and mean time to relapse of disease (MD 59.93 days, 95% CI 19.02 to 100.84). Mean time to relapse was significantly shorter for patients receiving budesonide than for those receiving azathioprine (MD -58.00, 95% CI -96.68 to -19.32). Adverse events were not more common in patients treated with budesonide compared to placebo (6 mg: RR 1.51, 95% CI 0.90 to 2.52; 3 mg: RR 1.19, 95% CI 0.63 to 2.24). These events were relatively minor and did not result in increased rates of study withdrawal. Commonly reported treatment-related adverse effects included acne, moon facies, hirsutism, mood swings, insomnia, weight gain, striae, and hair loss. Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg (RR 2.88, 95% CI 1.72 to 4.82) and 3 mg daily (RR 2.73, 95% CI 1.34 to 5.57) compared to placebo. AUTHORS' CONCLUSIONS These data suggest budesonide is not effective for maintenance of remission in CD, particularly when used beyond three months following induction of remission. Budesonide does have minor benefits in terms of lower CDAI scores and longer time to relapse of disease. However, these benefits are offset by higher treatment-related adverse event rates and more frequent adrenocorticoid suppression in patients receiving budesonide.
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Affiliation(s)
- M Ellen Kuenzig
- The Children's Hospital of Eastern OntarioDivision of Gastroenterology Hepatology & Nutrition401 Smyth RoadOttawaONCanadaK1H 8L1
- University of CalgaryDepartment of Community Health SciencesCalgaryABCanada
| | - Ali Rezaie
- Cedars‐Sinai Medical CenterDepartment of MedicineLos AngelesCaliforniaUSA90048
| | - Cynthia H Seow
- University of CalgaryDepartment of Community Health SciencesCalgaryABCanada
- University of CalgaryDepartment of MedicineTRW Building Rm 6D183280 Hospital Drive NWCalgaryABCanadaT2N 4Z6
| | - Anthony R Otley
- IWK Health CentreHead, Division of Gastroenterology5850 University AvenueHalifaxNSCanadaB3K 6R8
| | - A. Hillary Steinhart
- Mount Sinai HospitalDepartment of Medicine, Division of GastroenterologyRoom 445, 600 University AvenueTorontoONCanadaM5G 1X5
| | - Anne Marie Griffiths
- The Hospital for Sick ChildrenDivision of Gastroenterology, Hepatology & Nutrition555 University Ave.TorontoONCanadaM5G 1X8
| | - Gilaad G Kaplan
- University of CalgaryDepartment of Community Health SciencesCalgaryABCanada
- University of CalgaryDepartment of MedicineTRW Building Rm 6D183280 Hospital Drive NWCalgaryABCanadaT2N 4Z6
| | - Eric I Benchimol
- The Children's Hospital of Eastern OntarioDivision of Gastroenterology Hepatology & Nutrition401 Smyth RoadOttawaONCanadaK1H 8L1
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Abstract
Crohn disease (CD) is one of the major subtypes of inflammatory bowel disease and can occur in any segment of the alimentary tract. There have been significant advances in the medical therapy of CD over the past several decades. For mild CD, the oral corticosteroid derivative budesonide has demonstrated superior efficacy compared with traditional therapies such as 5-aminosalicylic acid, and can be used concurrently with these agents. For the management of moderate to severe disease, the immunomodulators azathioprine, 6-mercaptopurine, and methotrexate, as well as the antitumor necrosis factor-alpha (TNF-α) agents infliximab, adalimumab, and certolizumab pegol, have become the mainstay of therapy, with growing interest in combining these agents for maximal effect. Immunomodulators and anti-TNF-α agents have also demonstrated benefit in fistulizing CD. There has been growing evidence suggesting that both of these agents, along with the antibiotics metronidazole and ornidazole, are also effective in preventing postoperative recurrence of CD.
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Affiliation(s)
- Frank I Scott
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Penn Presbyterian Medical Center, Philadelphia, Pennsylvania
| | - Mark T Osterman
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Penn Presbyterian Medical Center, Philadelphia, Pennsylvania
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Garg SK, Croft AM, Bager P. Helminth therapy (worms) for induction of remission in inflammatory bowel disease. Cochrane Database Syst Rev 2014; 2014:CD009400. [PMID: 24442917 PMCID: PMC10767620 DOI: 10.1002/14651858.cd009400.pub2] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, globally-occurring gastrointestinal disorder and a major cause of illness and disability. It is conventionally classified into Crohn's disease (CD) and ulcerative colitis (UC). Helminths are parasitic worms with complex life cycles involving tissue- or lumen-dwelling stages in their hosts, and causing long-lasting or chronic infections that are frequently asymptomatic. Helminths modulate immune responses of their hosts, and many observational and experimental studies support the hypothesis that helminths suppress immune-mediated chronic inflammation that occurs in asthma, allergy and IBD. OBJECTIVES The objective was to evaluate the efficacy and safety of helminth treatment for induction of remission in IBD. SEARCH METHODS We searched the following databases from inception to 13 July 2013: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register. We also searched four online trials registries, and abstracts from major meetings. There were no language restrictions. SELECTION CRITERIA Randomised controlled trials (RCTs) where the intervention was any helminth species or combination of helminth species, administered in any dose and by any route and for any duration of exposure to people with active CD or UC, confirmed through any combination of clinical, endoscopic and histological criteria were eligible for inclusion. DATA COLLECTION AND ANALYSIS Two authors independently extracted data and assessed eligibility using a standardized data collection form. We used the RevMan software for analyses. The primary outcome was induction of remission as defined by the included studies. Secondary outcomes included clinical, histologic, or endoscopic improvement as defined by the authors, endoscopic mucosal healing, change in disease activity index score, change in quality of life score, hospital admissions, requirement for intravenous corticosteroids, surgery, study withdrawal and the incidence of adverse events. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We calculated the mean difference (MD) and 95% CI for continuous outcomes. We assessed the methodological quality of included studies using the Cochrane risk of bias tool. The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. MAIN RESULTS Two RCTs (90 participants) were included. One trial assessed the efficacy and safety of Trichuris suis (T. suis) ova in patients with UC (n = 54). The other RCT was a phase one that assessed the safety and tolerability of T. suis ova in patients with CD (n = 36). The risk of bias in both studies was judged to be low. In the UC study, during the 12-week study period, participants in the active arm received 2-weekly aliquots of 2500 T. suis eggs, added to 0.8 mL of saline; those in the placebo arm received 0.8 mL saline only. There were sparse data available for the outcomes clinical remission and clinical improvement. Ten per cent (3/30) of patients in the T. suis arm entered remission compared to 4% (1/24) of patients in the placebo arm (RR 2.40, 95% CI 0.27 to 21.63). Forty-three per cent (13/30) of patients in the T. suis group achieved clinical improvement compared to 17% (4/24) of placebo patients (RR 2.60, 95% CI 0.97 to 6.95). The mean ulcerative colitis disease activity index (UCDAI) score was lower in the T. suis group (6.1 +/- 0.61) compared to the placebo group (7.5 +/- 0.66) after 12 weeks of treatment (MD -1.40, 95% CI -1.75 to -1.05). There was only limited evidence relating to the proportion of patients who experienced an adverse event. Three per cent (1/30) of patients in the T. suis group experienced at least one adverse event compared to 12% (3/24) of placebo patients (RR 0.27, 95% CI 0.03 to 2.40). None of the adverse events reported in this study were judged to be related to the study treatment. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission and improvement) as low due to serious imprecision. In the CD study, participants received a single treatment of T. suis ova at a dosage of 500 (n = 9), 2500 (n = 9), or 7500 (n = 9) embryonated eggs or matching placebo (n = 9). The CD study did not assess clinical remission or improvement as outcomes. There were sparse data on adverse events at two weeks. Thirty-seven per cent (10/27) of patients in the T. suis group experienced at least one adverse event compared to 44% (4/9) of placebo patients (RR 0.83, 95% CI 0.35 to 2.01). Only one adverse event (dysgeusia) was judged to be possibly related to treatment in this study. Dysgeusia was reported in one patient in the T. suis group and in one patient in the placebo group. AUTHORS' CONCLUSIONS Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of helminths used to treat patients with IBD. The evidence for our primary efficacy outcomes in this review comes from one small study and is of low quality due to serious imprecision. We do not have enough evidence to determine whether helminths are safe when used in patients with UC and CD. Further RCTs are required to assess the efficacy and safety of helminth therapy in IBD.
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Affiliation(s)
- Sushil K Garg
- University of MinnesotaDepartment of Surgery420 Delaware Street SEMayo Mail Code 195MinneapolisMNUSA55455
| | - Ashley M Croft
- Ministry of DefenceSurgeon General's DepartmentLondonUKSW1A 2HA
| | - Peter Bager
- Statens Serum InstitutDepartment of Epidemiology ResearchØrestads Boulevard 5CopenhagenDenmarkDK‐2300
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Chhaya V, Pollok R. The impact of thiopurines on surgical outcomes in inflammatory bowel disease: do they make a difference? F1000PRIME REPORTS 2013; 5:50. [PMID: 24273651 PMCID: PMC3816845 DOI: 10.12703/p5-50] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Ulcerative colitis and Crohn's disease together are known as inflammatory bowel disease (IBD). Surgery is considered for more severe disease and is a dreaded consequence for patients. Thiopurines have proven efficacy in the induction and maintenance of remission of IBD, but the long-term need for surgery remains uncertain with conflicting results from the available studies. The timing and duration of thiopurines also appears to play a pivotal role in the management of these conditions and may also affect the need for surgery. Data from Denmark, Canada, Hungary and the UK appear to suggest a reduction in surgery rates prior to the introduction of anti-tumor necrosis factor (TNF) therapy. The authors aim to review the more recent literature evaluating the surgery rates in IBD and changes in disease trends over time. We ask whether increasing thiopurine prescribing has had an effect on the surgery rates in the era of biologic therapy and whether more aggressive treatment approaches have altered the natural history of IBD.
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Curkovic I, Egbring M, Kullak-Ublick GA. Risks of inflammatory bowel disease treatment with glucocorticosteroids and aminosalicylates. Dig Dis 2013; 31:368-73. [PMID: 24246990 DOI: 10.1159/000354699] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Glucocorticosteroids and aminosalicylates, mainly mesalazine (5-ASA), are both standard therapeutics in the treatment of inflammatory bowel disease (IBD) patients. The glucocorticosteroids are highly effective in inducing remission in both ulcerative colitis and Crohn's disease, but their use is limited by the high incidence and the potentially serious nature of adverse events. In an attempt to limit systemic side effects, rapidly metabolized corticosteroids such as budesonide have been introduced. The safety profile of aminosalicylates differs between the formulations. METHODS We summarize the potential risks associated with glucocorticosteroid and aminosalicylate therapy in IBDs. RESULTS The numerous adverse events of glucocorticosteroids, particularly at high doses and prolonged treatment, include opportunistic infections, diabetes mellitus, hypertension, ocular effects (glaucoma and cataracts), psychiatric complications, hypothalamic-pituitary-adrenal axis suppression and increased fracture risk. Partially, these systemic adverse events occur with budesonide, which only has a low systemic exposure. The safety profile of 5-ASA is comparable to placebo and superior to the old aminosalicylate prodrug sulfasalazine, which had a significantly higher incidence of intolerance reactions including allergic rashes. Only in rare cases has nephrotoxicity such as interstitial nephritis been associated with 5-ASA. CONCLUSION Considering the toxicity profile of conventional glucocorticosteroids, one primary goal of treatment in IBD should be corticosteroid-free remission. Therapy with budesonide may result in a better safety profile. 5-ASA treatment is usually well tolerated, but with regard to the rare nephrotoxic events, it is advisable to assess renal function before and during treatment with 5-ASA.
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Affiliation(s)
- Ivanka Curkovic
- Department of Clinical Pharmacology and Toxicology, University Hospital Zürich, Zürich, Switzerland
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27
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Practical medical management of Crohn's disease. ISRN GASTROENTEROLOGY 2013; 2013:208073. [PMID: 24307950 PMCID: PMC3838825 DOI: 10.1155/2013/208073] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 09/01/2013] [Indexed: 12/14/2022]
Abstract
Crohn's disease is a chronic inflammatory disease of diagnostic and therapeutic challenges. After proper diagnosis, treatment decisions must be made on precise clinical judgment. During the course of the disease there are variable clinical features, so each case must be managed individually. Physicians who care for patients with Crohn's disease should be prepared for treatment options in different states of the disease and possible complications of both the disease and medications. This paper will focus on the management of Crohn's disease. We aim to discuss current treatment options in different presentations of the disease and to provide algorithmic management strategy.
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Han J, Wang J, Wang JH. How to achieve deep remission in the treatment of inflammatory bowel disease. J TRADIT CHIN MED 2013; 33:549-52. [DOI: 10.1016/s0254-6272(13)60164-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Abstract
In recent years, a change in the treatment goals for patients with Crohn's disease (CD) has come under intense discussion. Whereas 10 years ago treatment was initiated mainly in reaction to acute flares of the disease aimed to improve clinical symptoms, the focus now has changed to the prevention of damage to the intestinal wall. The prevention of structural damage by achievement of 'mucosal healing', however, is associated with the more 'aggressive' treatment and an earlier use of immunosuppressants and biologicals. The use of immunosuppressants and biologicals especially in patients with CD has decreased the rates of surgery and hospitalizations, indicating that there is a group of patients definitely profiting from such an early use of immunosuppressive treatment. In this group of patients, the benefits outweigh the disadvantages of immunosuppression: the increased risk of severe infections. However, it remains questionable whether this improvement can only be achieved by completely reversing established treatment strategies. The dispute has been condensed to the questions whether 'top-down' (e.g. start with a combination of biological and immunosuppressant and 'de-escalate' if possible) or 'step-up' treatment (e.g. start with topical steroids, step up to systemic steroid, go to immunosuppression and biologicals if necessary) may be better. In general, in an upcoming era of individualized and personalized medicine, a 'one-size-fits-all' approach does not appear to be desirable. CD patients definitely should not be undertreated (which is still frequently the case) or remain on steroid treatment (which is inappropriate); however, overtreatment (putting patients at risk of side effects without benefit) is against a fundamental principle of medicine: nihil nocere (do no harm).
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Affiliation(s)
- Gerhard Rogler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zürich, Zürich, Switzerland.
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Abstract
IMPORTANCE Treatment of Crohn disease is rapidly evolving, with the induction of novel biologic therapies and newer, often more intensive treatment approaches. Knowing how to treat individual patients in this quickly changing milieu can be a challenge. OBJECTIVE To review the diagnosis and management of moderate to severe Crohn disease, with a focus on newer treatments and goals of care. EVIDENCE REVIEW MEDLINE was searched from 2000 to 2011. Additional citations were procured from references of select research and review articles. Evidence was graded using the American Heart Association level-of-evidence guidelines. RESULTS Although mesalamines are still often used to treat Crohn disease, the evidence for their efficacy is lacking. Corticosteroids can be effectively used to induce remission in moderate to severe Crohn disease, but they do not maintain remission. The mainstays of treatment are immunomodulators and biologics, particularly anti-tumor necrosis factor. CONCLUSION AND RELEVANCE Immunomodulators and biologics are now the preferred treatment options for Crohn disease.
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Affiliation(s)
- Adam S Cheifetz
- Division of Gastroenterology, Rabb-Rose 425, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA.
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Prantera C, Marconi S. Glucocorticosteroids in the treatment of inflammatory bowel disease and approaches to minimizing systemic activity. Therap Adv Gastroenterol 2013; 6:137-56. [PMID: 23503968 PMCID: PMC3589135 DOI: 10.1177/1756283x12473675] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions characterized by chronic, uncontrolled inflammation of the gastrointestinal tract. Reported prevalence is high in the United States and northern Europe, while the incidence varies greatly across the rest of Europe. Glucocorticosteroids are the standard treatment for IBD, but due to adverse events their use can be limited. However, new formulations of glucocorticosteroids have been developed to reduce systemic activation. The aim of this review was to assess and summarize the efficacy and safety of new formulations of glucocorticosteroids. A MEDLINE search identified publications focused on new formulations of nonsystemic steroid-based drugs for IBD and benefits and limitations of each of the new glucocorticosteroid formulations were identified. Budesonide has good efficacy and is an established treatment for Crohn's disease; it has been shown to be beneficial for the induction of remission in these patients, although it is not recommended for the maintenance of induced remission. Glucocorticosteroids are not recommended for the maintenance of remission in patients with IBD. However, a recent study suggested that beclomethasone dipropionate may be effective for prolonged treatment in patients in the postacute phase of Crohn's disease who were treated with a short course of systemic steroids. The efficacy of fluticasone propionate and prednisolone metasulphobenzoate in IBD is not well established given the small number of patients enrolled in the few published clinical trials. While the tolerability of these glucocorticosteroids is favourable, more research comparing these new agents with traditional systemic glucocorticosteroids is warranted.
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Affiliation(s)
- Cosimo Prantera
- Azienda Ospedaliera San Camillo Forlanini, via Monterosi 116, 00191 Rome, Italy
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32
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Hall PSJ, Allen PB, Diong KL, Varghese A. If it walks like Crohn's and talks like Crohn's, it must be... BMJ Case Rep 2013; 2013:bcr-2012-008051. [PMID: 23314454 DOI: 10.1136/bcr-2012-008051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 30-year-old man presented with a 6- month history of nausea, vomiting and diarrhoea. This was associated with 25 kg weight loss and a right-sided abdominal colic. He had been provisionally diagnosed with Crohn's disease 6 months back and treated with budesonide and mesalazine. Investigations including C reactive protein, white cell count, coeliac antibodies, fasting gut hormones and faecal elastase were all normal. Colonoscopy and ileoscopy were normal both macroscopically and microscopically. Small bowel series and labelled white cell scan were both unremarkable. A CT scan suggested the presence of mild right-sided abdominal lymphadenopathy. Laparoscopy of entire small bowel and colon was normal. But had something been missed? An adrenocorticotrophic hormone stimulation test demonstrated inadequate cortisol response and a diagnosis of adrenal insufficiency was confirmed. Addison's disease can present with a variety of gastrointestinal symptoms and should be considered in the diagnostic work-up of these patients.
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Affiliation(s)
- Philip S J Hall
- Department of Gastroenterology, Altnagelvin Hospital, Londonderry, UK
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Melter M, Buderus S. Pharmakologische Aspekte. PÄDIATRISCHE GASTROENTEROLOGIE, HEPATOLOGIE UND ERNÄHRUNG 2013. [PMCID: PMC7498793 DOI: 10.1007/978-3-642-24710-1_47] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Kortikosteroide waren die ersten Therapeutika zur Kontrolle von Abstoßungsreaktionen nach Transplantation. Sie sind seit Langem und immer noch wichtiger Bestandteil vieler immunsuppressiver Therapiekonzepte. Kortikosteroide besitzen zahlreiche antiinflammatorische und immunsuppressive Effekte. Sie beeinflussen über die Bindung spezifischer zytoplasmatischer Rezeptoren die Gentranskriptionsrate für zentrale, immunregulatorische Proteine wie Interleukin 1β (IL-1β), IL-6, Tumor-Nekrose-Faktor α (TNF-α) mit resultierender Suppression der Makrophagenfunktion und konsekutiver T-Zell-Aktivierung. Sie inhibieren auch die IL-2-Synthese, hemmen damit die T-Zell-Proliferation und reduzieren die IL- 2-Rezeptorbindungsfähigkeit. Andererseits stimulieren sie die Synthese des inhibierenden Zytokins „transforming growth factor β“ (TGF-β), was in einem „antiinflammatorisch“ geprägten T-Helfer-Zell-2-artigen Zytokinprofil resultiert. Über die Inhibition der Expression von interferonabhängigen Adhäsionsmolekülen (einschließlich MHC-Klasse-II-Moleküle) bewirken Kortikosteroide darüber hinaus die Alteration von Leukozytenverkehr und -transmigration sowie eine Induktion der Lymphozytenapoptose.
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34
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Ueno F, Matsui T, Matsumoto T, Matsuoka K, Watanabe M, Hibi T. Evidence-based clinical practice guidelines for Crohn's disease, integrated with formal consensus of experts in Japan. J Gastroenterol 2013; 48:31-72. [PMID: 23090001 PMCID: PMC3541931 DOI: 10.1007/s00535-012-0673-1] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2012] [Accepted: 08/16/2012] [Indexed: 02/04/2023]
Abstract
Crohn's disease is a disorder of unknown etiology and complicated pathogenesis. A substantial amount of evidence has accumulated recently and has been applied to clinical practice. The present guidelines were developed based on recent evidence and the formal consensus of experts relevant to this disease. Here we provide an overview of these guidelines, as follows. Target disease: Crohn's disease Users: Clinical practitioners in internal medicine, surgery, gastroenterology, and general practice Purpose: To provide appropriate clinical indicators to practitioners Scope of clinical indicators: Concept of Crohn's disease, epidemiology, classifications, diagnosis, treatment, follow up, and special situations Intervention: Diagnosis (interview, physical examination, clinical laboratory tests, imaging, and pathology) and treatment (lifestyle guidance, drug therapy, nutritional therapy, surgery, etc.) Outcome assessment: Attenuation of symptoms, induction and maintenance of remission, imaging findings, quality of life (QOL), prevention of complications and harm of therapy Methods for developing these guidelines: Described in the text Basis of recommendations: Integration of evidence level and consensus of experts Cost-benefit analysis: Not implemented Evaluation of effectiveness: Yet to be confirmed Status of guidelines: Updated version of the first Guidelines published in 2010 Publication sources: Printed publication available and electronic information in preparation Patient information: Not available Date of publication: October 2011 These guidelines were intended primarily to be used by practitioners in Japan, and the goal of these guidelines is to improve the outcomes of patients with Crohn's disease.
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Affiliation(s)
| | - Toshiyuki Matsui
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Takayuki Matsumoto
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshifumi Hibi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
| | - On Behalf of the Guidelines Project Group of the Research Group of Intractable Inflammatory Bowel Disease subsidized by the Ministry of Health, Labour and Welfare of Japan and the Guidelines Committee of the Japanese Society of Gastroenterology
- Ofuna Chuo Hospital, Kanagawa, Japan
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
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O'Donnell S, O'Morain CA. Therapeutic benefits of budesonide in gastroenterology. Ther Adv Chronic Dis 2012; 1:177-86. [PMID: 23251737 DOI: 10.1177/2040622310379293] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Budesonide is a synthetic steroid of the glucocorticoid family with a high topical anti-inflammatory activity. Enteric-coated formulations resist gastric-acid degradation, delivering active drug to the small intestine and proximal colon. Budesonide has a high first-pass metabolism with minimal systemic absorption. It is therefore felt to cause fewer side effects than traditional glucocorticosteroids and to be generally well tolerated. The aim of this paper is to examine the utility of this medication in frequently encountered gastrointestinal conditions: Crohn's disease, ulcerative colitis, microscopic colitis and eosinophilic oesophagitis. A Medline search was performed to find published original research and review articles relating to the use budesonide in common gastroenterological conditions. The results showed that budesonide is efficacious in the induction and short-term maintenance of Crohn's disease. Budesonide is the best-documented treatment for microscopic colitis. It is well proven to be effective in the induction of remission in collagenous colitis but its use in lymphocytic colitis remains less well documented. In conclusion, budesonide is an effective glucocorticosteroid therapy for many chronic gastrointestinal diseases. In combination with its efficacy, the low incidence of serious side effects associated with this drug should keep it at the forefront in the therapeutic arsenal of any gastroenterologist.
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Affiliation(s)
- Sarah O'Donnell
- Colm A. O'Morain, DSc (University of London), DSc Honoris Causa (University of Athens), MSc, MD, MA, Dip. Imm., FACG, FEBG, FRCP, FRCPI, FTCD, AGAF, Consultant Gastroenterologist, Professor of Medicine, Dean of Health Sciences Department of Gastroenterology, AMNCH/Trinity College Dublin, Dublin, Ireland
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36
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Abstract
Pediatric inflammatory bowel disease encompasses a spectrum of disease phenotype, severity, and responsiveness to treatment. Intestinal healing rather than merely symptom control is an especially important therapeutic goal in young patients, given the potential for growth impairment as a direct effect of persistent chronic inflammation and the long life ahead, during which other disease complications may occur. Corticosteroids achieve rapid symptom control, but alternate steroid-sparing strategies with greater potential to heal the intestine must be rapidly adopted. Exclusive enteral nutrition is an alternate short-term treatment in pediatric Crohn's disease. The results of multi-center pediatric clinical trials of both infliximab and adalimumab in Crohn's disease and of infliximab in ulcerative colitis (all in children with unsatisfactory responses to other therapies) have now been reported and guide treatment regimens in clinical practice. Optimal patient selection and timing of anti-TNF therapy requires clinical judgment. Attention must be paid to sustaining responsiveness safely.
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Affiliation(s)
- Mary E Sherlock
- Division of Gastroenterology, McMaster Children's Hospital, Hamilton, Canada.
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37
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Abstract
Treatment goals in Crohn's disease are evolving beyond the control of symptoms. A treat-to-target approach to management that features earlier initiation of TNF antagonist therapy will enable resolution of objective parameters of inflammation. The decision to initiate anti-TNF therapy should be based on a patient-specific assessment of risks and benefits. This paradigm necessitates a complex process, influenced by multiple factors that include the quality of data available, physicians' and patients' knowledge of the data, and the preferences and values of patients, physicians and society. The potential 'opportunity cost' resulting from a delay in initiation of effective therapy, a consideration that has been neglected in the past, must also enter into the equation. Our evolving approach to the management of Crohn's disease challenges patients to participate in the decision-making process and to become an active partner in their care. Ideally, this evolution should occur within the context of an enduring physician/patient relationship that is based on mutual trust. Motivational communication provides a useful technique to improve dialogue and collaboration between healthcare professionals and patients, and may help to engage and motivate patients to commit to managing their disease.
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38
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Panaccione R, Hibi T, Peyrin-Biroulet L, Schreiber S. Implementing changes in clinical practice to improve the management of Crohn's disease. J Crohns Colitis 2012; 6 Suppl 2:S235-42. [PMID: 22463930 DOI: 10.1016/s1873-9946(12)60503-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The introduction of anti-tumour necrosis factor therapies has provided highly effective treatments for Crohn's disease, making it possible to significantly improve the prognosis of patients. However, neither conventional non-biological therapies nor anti-tumour necrosis factor therapies are routinely used to optimum effect. There are several reasons for this, including a lack of specific evidence to guide common clinical questions and a lack of clearly defined treatment targets. This paper suggests some simple changes to the management of Crohn's disease that have the potential to significantly improve patient outcomes. A new treatment target, 'deep remission', which includes mucosal healing as well as clinical remission, may be the first step in defining the successful treatment of Crohn's disease; early clinical studies have demonstrated that this is a readily achievable target. Initiating appropriate treatment early can increase clinical remission rates, improve steroid sparing, induce mucosal healing and prevent structural bowel damage, whereby reducing the need for hospitalization and surgery. There are also clear indications that modifying treatment based on regular objective assessments of disease activity to provide tight disease control can improve patient outcomes in a similar way to that observed in rheumatoid arthritis. These simple changes to management strategy appear to allow the full potential of available treatments to be realized. Clinical studies to further define optimized treatment strategies for Crohn's disease are underway and will provide future direction.
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Affiliation(s)
- Remo Panaccione
- Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, Canada.
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39
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Buchner AM, Blonski W, Lichtenstein GR. Update on the management of Crohn's disease. Curr Gastroenterol Rep 2012; 13:465-74. [PMID: 21792543 DOI: 10.1007/s11894-011-0220-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Crohn's disease (CD) is a chronic inflammatory disorder characterized by focal, asymmetric, transmural inflammation of any part of the luminal gastrointestinal tract of uncertain etiology and an unpredictable course. The available treatment options include aminosalicylates, budesonide and systemic corticosteroids, antibiotics, immunomodulators,methotrexate and anti-TNF agents. This review discusses recent developments in the treatment of CD and provides a comprehensive update on management of patients with CD based on the data from randomized controlled trials.
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Affiliation(s)
- Anna M Buchner
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA
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40
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Roth L, Macdonald JK, McDonald JW, Chande N. Sargramostim (GM-CSF) for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2011:CD008538. [PMID: 22071853 DOI: 10.1002/14651858.cd008538.pub2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Crohn's disease is an inflammatory condition of the gut, thought to involve an overactive immune response to gut flora. A novel theory postulates possible immunodeficiency as a cause, and aims to use sargramostim (granulocyte macrophage colony stimulating factor, GM-CSF) to boost the immune system in an effort to test this hypothesis. OBJECTIVES The primary objectives were to determine the efficacy and safety of sargramostim for induction of remission in patients with clinically active Crohn's disease. SEARCH METHODS A systematic search of MEDLINE, EMBASE, and CENTRAL was conducted from inception to April 2011. Reference lists of relevant review articles were also searched. Trial registries and abstract databases including Digestive Diseases Week (1980-2010) and United European Gastroenterology Week (2005-2009) were searched to identify studies published in abstract form. SELECTION CRITERIA Randomized controlled trials of sargramostim for the treatment of patients with active Crohn's disease were considered for inclusion. DATA COLLECTION AND ANALYSIS Data from selected articles were extracted and the Cochrane Risk of Bias tool applied independently by two authors. The primary outcome was induction of clinical remission as defined by a Crohn's Disease Activity Index (CDAI) of < 150 at the end of treatment. Secondary outcomes included clinical responses measures on the CDAI and safety outcomes. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes, in most cases using a random effects model due to high heterogeneity. MAIN RESULTS Three studies were identified, 2 published as full papers and one in abstract form (537 patients). The risk of bias was low for the 3 included studies. There was no statistically significant difference in the proportion of patients (GM-CSF 25.3% versus placebo 17.5%) who achieved clinical remission (RR 1.67; 95% CI 0.80 to 3.50; P = 0.17; 3 studies; 537 patients). There was no statistically significant difference in the proportion of patients (GM-CSF 38.3% versus placebo 24.8%) who achieved a 100-point clinical response (RR 1.71 95% CI 0.98 to 2.97; P = 0.06; 3 studies; 537 patients). There was no statistically significant difference in the proportion of patients (GM-CSF 54.3% versus placebo 44.2%) who achieved a 70 point clinical response (RR 1.23; 95% CI 0.83 to 1.82; P = 0.30; 1 study; 124 patients). There was no statistically significant difference in the proportion of patients (GM-CSF 95.8% versus placebo 89.3%) who experienced at least one adverse event (RR 1.07; 95% CI 0.99 to 1.16; P = 0.08; 2 studies; 251 patients), or serious adverse events (GM-CSF 12.0% versus placebo 4.8%; RR 2.21; 95% CI 0.84 to 5.81; P = 0.11; 2 studies; 251 patients). The incidence of bone pain, musculoskeletal chest pain, and dyspnea were higher in patients treated with sargramostim compared to placebo. Other adverse events commonly associated with sargramostim such as pulmonary capillary leak syndrome, pulmonary edema, heart failure, fever, and neurotoxicity were not reported in these studies. AUTHORS' CONCLUSIONS Sargramostim does not appear to be more effective than placebo for induction of clinical remission or clinical improvement in patients with active Crohn's disease. However, the GRADE analysis indicates that the overall quality of the evidence for the primary (clinical remission) and secondary outcomes (clinical response) was low indicating that further research is likely to have an impact on the effect estimates.
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Affiliation(s)
- Lee Roth
- London Health Sciences Centre - Victoria Hospital, London, Canada
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Abstract
The majority of patients with IBD use conventional therapy (namely, aminosalicylates, antibiotics, corticosteroids and immunomodulatory agents) for prolonged periods of time, to both induce and maintain remission. Treatment paradigms in IBD have evolved towards a rapid escalation of therapy to achieve stringent goals, including mucosal healing and a reduction in the need for hospital admission and surgery. In this context, the failure to optimize conventional therapy can lead to a potentially effective treatment being abandoned too early, which is undesirable when only a limited number of drugs are effective in the management of IBD, and could also lead to patients being unnecessarily exposed to potentially toxic and/or expensive biologic drugs. This Review provides an overview of the many ways in which conventional therapy can be optimized, and describes strategies to improve adherence to drug regimens, such as simplifying the dosing regimen, optimizing drug delivery and dose, and tailoring medication on the basis of metabolite levels.
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Affiliation(s)
- Kirstin M Taylor
- Department of Gastroenterology, Guy's & St Thomas' Hospitals, Westminster Bridge Road, London SE1 7EH, UK
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Stewart MJ, Seow CH, Storr MA. Prednisolone and budesonide for short- and long-term treatment of microscopic colitis: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2011; 9:881-90. [PMID: 21699817 DOI: 10.1016/j.cgh.2011.06.005] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2011] [Revised: 05/18/2011] [Accepted: 06/04/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The incidence of microscopic colitis and its disease burden are increasing, yet there is limited systematic information addressing the use of conventional corticosteroids and budesonide in microscopic colitis. We performed a systematic review and meta-analysis on the short- and long-term efficacy of corticosteroids in treatment of microscopic colitis. METHODS Randomized controlled trials that met predetermined selection criteria were included. Articles were identified through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, proceedings of major gastroenterology meetings, and reference lists of trials and review articles. RESULTS Eight randomized trials were identified. A total of 248 patients were randomized to corticosteroid versus placebo. The intervention was budesonide in 7 trials and prednisolone in 1 trial. Budesonide was significantly more effective than placebo for short-term clinical response (risk ratio [RR], 3.07; 95% confidence interval [CI], 2.06-4.57) and long-term clinical response (RR, 3.22; 95% CI, 1.05-9.89). Prednisolone was not superior to placebo for short-term clinical response (RR, 2.00; 95% CI, 0.38-10.58). Histologic improvement was seen with both short- and long-term budesonide (RR, 3.76; 95% CI, 2.00-7.06, and RR, 2.50; 95% CI, 1.25-4.98, respectively). Symptom relapse occurred in 46%-80% of patients within 6 months of treatment cessation. Withdrawal because of adverse effects occurred in 4.4% of patients, with no difference between study groups (P = .55). CONCLUSIONS Both short- and long-term treatment with budesonide is effective and well-tolerated for microscopic colitis. However, the rate of symptom relapse once budesonide is discontinued is high. Further studies are needed to determine optimal treatment duration, dose, and withdrawal procedure.
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Affiliation(s)
- Michael J Stewart
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
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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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Burger D, Travis S. Conventional medical management of inflammatory bowel disease. Gastroenterology 2011; 140:1827-1837.e2. [PMID: 21530749 DOI: 10.1053/j.gastro.2011.02.045] [Citation(s) in RCA: 163] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2010] [Revised: 01/31/2011] [Accepted: 02/04/2011] [Indexed: 02/08/2023]
Abstract
Conventional therapies for ulcerative colitis and Crohn's disease (CD) include aminosalicylates, corticosteroids, thiopurines, methotrexate, and anti-tumor necrosis factor agents. A time-structured approach is required for appropriate management. Traditional step-up therapy has been partly replaced during the last decade by potent drugs and top-down therapies, with an accelerated step-up approach being the most appropriate in the majority of patients. When patients are diagnosed with CD or ulcerative colitis, physicians should consider the probable pattern of disease progression so that effective therapy is not delayed. This can be achieved by setting arbitrary time limits for administration of biological therapies, changing therapy from mesalamine in patients with active ulcerative colitis, or using rescue therapy for acute severe colitis. In this review, we provide algorithms with a time-structured approach for guidance of therapy. Common mistakes in conventional therapy include overprescription of mesalamine for CD; inappropriate use of steroids (for perianal CD, when there is sepsis, or for maintenance); delayed introduction or underdosing with azathioprine, 6-mercaptopurine, or methotrexate; and failure to consider timely surgery. The paradox of anti-tumor necrosis factor therapy is that although it too is used inappropriately (when patients have sepsis or fibrostenotic strictures) or too frequently (for diseases that would respond to less-potent therapy), it is also often introduced too late in disease progression. Conventional drugs are the mainstay of current therapy for inflammatory bowel diseases, but drug type, timing, and context must be optimized to manage individual patients effectively.
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Affiliation(s)
- Daniel Burger
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom
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Gionchetti P, Calabrese C, Tambasco R, Brugnera R, Straforini G, Liguori G, Fornarini GS, Riso D, Campieri M, Rizzello F. Role of conventional therapies in the era of biological treatment in Crohn’s disease. World J Gastroenterol 2011; 17:1797-806. [PMID: 21528051 PMCID: PMC3080713 DOI: 10.3748/wjg.v17.i14.1797] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2010] [Revised: 07/12/2010] [Accepted: 07/19/2010] [Indexed: 02/06/2023] Open
Abstract
Outstanding progress regarding the pathophysiology of Crohn’s disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized, placebo-controlled trials, and meta-analyses when available, that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD, modifying the treatment goals. However, the large majority of patients with CD will be managed through conventional therapy, even if they are a prelude to biological therapy.
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Tromm A, Bunganič I, Tomsová E, Tulassay Z, Lukáš M, Kykal J, Bátovský M, Fixa B, Gabalec L, Safadi R, Kramm HJ, Altorjay I, Löhr H, Koutroubakis I, Bar-Meir S, Stimac D, Schäffeler E, Glasmacher C, Dilger K, Mohrbacher R, Greinwald R. Budesonide 9 mg is at least as effective as mesalamine 4.5 g in patients with mildly to moderately active Crohn's disease. Gastroenterology 2011; 140:425-434.e1; quiz e13-4. [PMID: 21070781 DOI: 10.1053/j.gastro.2010.11.004] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2010] [Revised: 10/21/2010] [Accepted: 11/03/2010] [Indexed: 01/09/2023]
Abstract
BACKGROUND & AIMS Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in patients with mildly to moderately active CD. METHODS We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L-coated oral mesalamine (4.5 g/day). RESULTS The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, -4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups. CONCLUSIONS Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L-coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen.
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Affiliation(s)
- Andreas Tromm
- Ev. Krankenhaus Hattingen GmbH, Klinik für Innere Medizin, Hattingen, Germany.
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Muratori L, Muratori P, Granito A, Pappas G, Cassani F, Lenzi M. Current topics in autoimmune hepatitis. Dig Liver Dis 2010; 42:757-764. [PMID: 20615766 DOI: 10.1016/j.dld.2010.05.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2010] [Revised: 05/23/2010] [Accepted: 05/31/2010] [Indexed: 12/11/2022]
Abstract
Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis.
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MESH Headings
- Animals
- Autoantibodies/immunology
- Autoantigens/immunology
- Biomarkers/blood
- Budesonide/therapeutic use
- Cholangitis, Sclerosing/complications
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/immunology
- Cholangitis, Sclerosing/therapy
- Cyclosporine/therapeutic use
- Glucocorticoids/therapeutic use
- Hepatitis, Autoimmune/complications
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/immunology
- Hepatitis, Autoimmune/therapy
- Humans
- Hypergammaglobulinemia
- Immunity, Cellular
- Immunoglobulin G/blood
- Immunosuppressive Agents/therapeutic use
- Liver Cirrhosis, Biliary/complications
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/immunology
- Liver Cirrhosis, Biliary/therapy
- Liver Transplantation/adverse effects
- Mice
- Mycophenolic Acid/analogs & derivatives
- Mycophenolic Acid/therapeutic use
- Rats
- Transaminases/blood
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Affiliation(s)
- Luigi Muratori
- Department of Clinical Medicine, Alma Mater Studiorum - University of Bologna, Policlinico Sant'Orsola-Malpighi, Padiglione 11, Bologna, Italy.
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Sherlock ME, Seow CH, Steinhart AH, Griffiths AM. Oral budesonide for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2010:CD007698. [PMID: 20927762 DOI: 10.1002/14651858.cd007698.pub2] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Corticosteroids remain one of the most popular medication choices for the induction of remission in ulcerative colitis and Crohn's disease. While corticosteroids may improve symptoms, they do not always result in mucosal healing and have significant adverse effects. Steroids which act topically, with less systemic side-effects may be more desirable. Oral budesonide, a topically acting corticosteroid with extensive first pass hepatic metabolism, is effective in Crohn's disease and in enema formulation for left-sided ulcerative colitis. Data are limited regarding the role of oral budesonide in ulcerative colitis. OBJECTIVES To systematically review the safety and efficacy of oral budesonide for induction of remission in ulcerative colitis. SEARCH STRATEGY Electronic searching of the MEDLINE and EMBASE databases was performed. Two authors independently reviewed all identified titles and abstracts. Full text articles of all potentially relevant studies were retrieved. Reference lists of review articles were searched in an attempt to identify additional studies. Abstracts of the major gastroenterology scientific meetings, held over the past 3 years, were hand searched. The ClinicalTrials.gov website as well as the Cochrane Registry of Controlled Trials was searched to identify any ongoing trials. Direct communication with pharmaceutical manufacturers was established to identify any ongoing or unpublished studies. SELECTION CRITERIA Randomized controlled trials of oral budesonide for the induction of remission in ulcerative colitis, with either a parallel arm or cross-over design, were considered eligible for inclusion. There were no exclusions based on patient age or the type, dose or duration of budesonide therapy. The primary outcome was the induction of clinical remission in ulcerative colitis. Secondary outcomes included clinical, histologic and endoscopic improvement, endoscopic mucosal healing, change in disease activity index scores, adverse events and study withdrawals. DATA COLLECTION AND ANALYSIS Studies were reviewed for eligibility, data were extracted and quality assessed by 2 independent investigators. It was not possible to perform a meta-analysis of the included studies due to significant heterogeneity, with each study comparing budesonide to a different control medication. MAIN RESULTS Three studies met the inclusion criteria. Oral budesonide was significantly less likely to induce clinical remission than oral mesalamine after 8 weeks of therapy (RR 0.72, 95% CI 0.57 to 0.91). There was no significant benefit of oral budesonide in comparison to placebo for inducing clinical remission after 4 weeks of treatment (RR 1.41, 95% CI 0.59 to 3.39). A small pilot study reported no statistically significant difference in endoscopic remission between budesonide and prednisolone (RR 0.75, 95% CI 0.23 to 2.42). The study was small and not powered to evaluate the impact of budesonide on clinical remission. Suppression of plasma cortisol was significantly more common in prednisolone treated patients (RR 0.02, 95% CI 0.0 to 0.33). Two multicenter studies are ongoing. AUTHORS' CONCLUSIONS At present, there is no evidence to recommend the clinical use of oral budesonide for the induction of remission in active ulcerative colitis. Mesalamine is superior to budesonide for the treatment of active ulcerative colitis.
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Affiliation(s)
- Mary E Sherlock
- Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8
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Consensus guidelines for the management of inflammatory bowel disease. ARQUIVOS DE GASTROENTEROLOGIA 2010; 47:313-325. [PMID: 21140096 DOI: 10.1590/s0004-28032010000300019] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2010] [Accepted: 07/20/2010] [Indexed: 12/16/2022]
Abstract
This is the first Brazilian Consensus on inflammatory bowel disease, carried out by the Brazilian Study Group of Inflammatory Bowel Disease, and discusses the treatment of Crohn's disease and ulcerative colitis in acute and remission phases. The first part of the text, brings out a review on the main drugs used in the treatment of inflammatory bowel disease, as well as their mechanisms of action and cautions during their use. In the second part, the committee's opinions about the most recommended medical and surgical approaches for both diseases are presented on the basis of disease activity, location and behaviour status. The recommendations here presented were widely discussed in several scientific meetings with active participation of all members of the group and were highly based on scientific evidence covered by the literature.
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Seow CH, de Silva S, Kaplan GG, Devlin SM, Ghosh S, Panaccione R. Managing the risks of IBD therapy. Curr Gastroenterol Rep 2010; 11:509-17. [PMID: 19903428 DOI: 10.1007/s11894-009-0077-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Successful management of the patient with inflammatory bowel disease (IBD) involves not only the induction and maintenance of remission, but also the optimization of the benefit-to-risk equation to achieve the greatest gain in quality of life. These risks range from intolerance to prescribed medications to potentially life-threatening sequelae (eg, sepsis) of immune suppression. A proper awareness of risk on the part of the physician and education of the patient can lead to early detection and institution of an appropriate management plan, including risk management and, optimally, primary prevention (eg, prophylactic vaccination). One should take the opportunity regularly to reassess the utility and efficacy of existing therapy, with the provision of ineffective therapies mandating urgent review. Overall, optimal management of the patient with IBD requires open dialogue between clinician and patient so that both are cognizant of the goals, benefits, and potential risks of therapy.
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Affiliation(s)
- Cynthia H Seow
- University of Calgary, TRW Building, Room 6D18, Calgary, Canada.
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