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1
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Ferretti F, Cannatelli R, Monico MC, Maconi G, Ardizzone S. An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis. J Clin Med 2022; 11:jcm11092302. [PMID: 35566428 PMCID: PMC9104748 DOI: 10.3390/jcm11092302] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/10/2022] [Accepted: 04/18/2022] [Indexed: 12/17/2022] Open
Abstract
The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients.
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Parfenov AI, Knyazev OV, Babayan AF, Kagramanova AV. Low adherence to treatment is a weak link in the problems of ulcerative colitis. TERAPEVT ARKH 2022; 93:1419-1427. [DOI: 10.26442/00403660.2021.12.201172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 01/14/2022] [Indexed: 01/10/2023]
Abstract
Aim. To determine factors of adherence to treatment in patients with ulcerative colitis (UC).
Materials and methods. The study was performed in the department of treatment of inflammatory bowel diseases in Loginov Moscow Clinical Scientific Center from 2019 till 2021 years by surveying 1089 patients with UC. This analysis revealed patients with high adherence (HAP) and low adherence to treatment (LAP).
Results. In the survey analysis was determined, that there were more low-adherence patients, than high-adherence patients [596 (59.6%) and 404 (40.4%), respectively, (р0.001)]. In the group of HAP (100%) were 297 women (73.5%) and 107 (26.5%) men (р0.001). Also in this group prevailed patients with duration of disease more 5 years 305 (75.5%) and extraintestinal manifestations 261 (64.6%); р0.001. In the group of LAP (100%) were more patients younger 44 years, with bad habits and who did not follow diet (р0.001). The rate of UC reccurence more than 1 time per year was higher in LAP group 430 (72.1%), versus 137 (33.9%) patients in HAP (р0.001). The frequency of surgical procedures in UC patients was significantly higher in LAP 12 (2.0%) in comparison with 2 (0.5%) in HAP group (р0.001).
Conclusion. In our study was determined, that among UC patients, examined in the department of inflammatory bowel diseases, 60% patients had low adherence to treatment. High adherence to the treatment is statistically significantly associated with female gender, family accommodation, non-working patients, extraintestinal manifestations, additional medical maintenance. Low adherence to the treatment is associated with steroids, male gender, age less than 44 year, bad habits (smoking, alcohol consumption), higher education, complicated UC and frequency of reccurences.
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3
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Tripathi K, Dong J, Mishkin BF, Feuerstein JD. Patient Preference and Adherence to Aminosalicylates for the Treatment of Ulcerative Colitis. Clin Exp Gastroenterol 2021; 14:343-351. [PMID: 34511961 PMCID: PMC8412827 DOI: 10.2147/ceg.s237653] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 08/14/2021] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disorder that requires sustained treatment for optimal outcomes. The 5-aminosalicylate (5-ASA) class of medications are first-line for the treatment of mild-to-moderate UC but suffer from suboptimal adherence rates in real-world settings. This review summarizes the literature on adherence and patient preference to 5-ASA in patients with UC. We begin by highlighting key studies that measure real-world adherence rates, as well as some of the pitfalls associated with certain techniques. We examine the data on the consequences of non-adherence, which range from decreased quality of life and higher risk of colorectal cancer at the individual level to increased costs to the overall healthcare system. We then turn to the reasons and risk factors for non-adherence and summarize the current understanding of the barriers towards adherence. Afterwards, we describe the research on patient preferences between 5-ASA formulations and dosing regimen. Finally, we summarize the evidence regarding interventions to improve 5-ASA adherence. While adherence remains a challenge in practice, understanding the current state of the field can better inform future efforts towards increasing adherence, and thus clinical outcomes, in UC.
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Affiliation(s)
- Kartikeya Tripathi
- Department of Gastroenterology, University of Massachusetts Medical School - Baystate Campus, Springfield, MA, USA
| | - Jeffrey Dong
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Brooke F Mishkin
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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4
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Kobayashi T, Siegmund B, Le Berre C, Wei SC, Ferrante M, Shen B, Bernstein CN, Danese S, Peyrin-Biroulet L, Hibi T. Ulcerative colitis. Nat Rev Dis Primers 2020; 6:74. [PMID: 32913180 DOI: 10.1038/s41572-020-0205-x] [Citation(s) in RCA: 877] [Impact Index Per Article: 175.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/21/2020] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. UC has evolved into a global burden given its high incidence in developed countries and the substantial increase in incidence in developing countries. An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. Since the early 2000s, anti-tumour necrosis factor (TNF) treatment has significantly improved treatment outcomes. Advances in medical treatments have enabled a paradigm shift in treatment goals from symptomatic relief to endoscopic and histological healing to achieve better long-term outcomes and, consequently, diagnostic modalities have also been improved to monitor disease activity more tightly. Despite these improvements in patient care, a substantial proportion of patients, for example, those who are refractory to medical treatment or those who develop colitis-associated colorectal dysplasia or cancer, still require restorative proctocolectomy. The development of novel drugs and improvement of the treatment strategy by implementing personalized medicine are warranted to achieve optimal disease control. However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.
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Affiliation(s)
- Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
| | - Britta Siegmund
- Division of Gastroenterology, Infectiology and Rheumatology, Charite-Universitatsmedizin, Berlin, Germany
| | - Catherine Le Berre
- Department of Gastroenterology, Nancy University Hospital, Inserm U1256 NGERE, Lorraine University, Lorraine, France
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Bo Shen
- Center for Inflammatory Bowel Diseases, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA
| | - Charles N Bernstein
- University of Manitoba IBD Clinical and Research Centre and Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Silvio Danese
- Humanitas Clinical and Research Center - IRCCS - and Humanitas University, Department of Biomedical Sciences, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Inserm U1256 NGERE, Lorraine University, Lorraine, France
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
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5
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Solitano V, D’Amico F, Fiorino G, Paridaens K, Peyrin-Biroulet L, Danese S. Key Strategies to Optimize Outcomes in Mild-to-Moderate Ulcerative Colitis. J Clin Med 2020; 9:jcm9092905. [PMID: 32911840 PMCID: PMC7564568 DOI: 10.3390/jcm9092905] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 09/04/2020] [Accepted: 09/07/2020] [Indexed: 12/11/2022] Open
Abstract
Mesalamine (5-ASA) is the mainstay therapy in patients with mild-to-moderate active ulcerative colitis (UC). However, non-adherence to therapy and practice variability among gastroenterologists represent long-standing barriers, leading to poor outcomes. Additionally, targets to treat in UC are increasingly evolving from focusing on clinical remission to achieving endoscopic and histological healing. To date, systemic steroids are still recommended in non-responders to 5-ASA, despite their well-known side effects. Importantly, with the advent of new therapeutic options such as oral corticosteroids with topical activity (e.g., budesonide multimatrix system (MMX)), biologics, and small molecules, some issues need to be addressed for the optimal management of these patients in daily clinical practice. The specific positioning of these drugs in patients with mild-to-moderate disease remains unclear. This review aims to identify current challenges in clinical practice and to provide physicians with key strategies to optimize treatment of patients with mild-to-moderate UC, and ultimately achieve more ambitious therapeutic goals.
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Affiliation(s)
- Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (V.S.); (F.D.); (G.F.)
| | - Ferdinando D’Amico
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (V.S.); (F.D.); (G.F.)
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, 54500 Vandoeuvre-lès-Nancy, France;
| | - Gionata Fiorino
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (V.S.); (F.D.); (G.F.)
- Department of Gastroenterology, IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, 20089 Milan, Italy
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, 54500 Vandoeuvre-lès-Nancy, France;
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (V.S.); (F.D.); (G.F.)
- Department of Gastroenterology, IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, 20089 Milan, Italy
- Correspondence: ; Tel.: +39-028-224-4771; Fax: +39-028-224-2591
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6
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Zhou Q, Shen ZF, Wu BS, Xu CB, He ZQ, Chen T, Shang HT, Xie CF, Huang SY, Chen YG, Chen HB, Han ST. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2019; 2019:5363261. [PMID: 31781191 PMCID: PMC6874962 DOI: 10.1155/2019/5363261] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 08/22/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. METHODS In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. FINDINGS We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. CONCLUSION In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.
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Affiliation(s)
- Qing Zhou
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhao-Feng Shen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ben-sheng Wu
- Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
| | - Cheng-biao Xu
- Xuyi Hospital of Traditional Chinese Medicine, Huaian, Jiangsu, China
| | - Zhong-qi He
- Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
| | - Tuo Chen
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hong-tao Shang
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chao-fan Xie
- Shishi General Hospital, Quanzhou, Fujian, China
| | - Si-yi Huang
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Yu-gen Chen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hai-bo Chen
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shu-tang Han
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Farrukh A, Mayberry JF. Surveillance for colorectal cancer and chemoprevention in ulcerative and Crohn's colitis: The need for clinical strategies to increase effectiveness. JGH Open 2019; 3:370-373. [PMID: 31633040 PMCID: PMC6788365 DOI: 10.1002/jgh3.12173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 02/16/2019] [Accepted: 02/24/2019] [Indexed: 11/26/2022]
Abstract
This review considers why current strategies for surveillance and the prevention of colorectal cancer as a long‐term complication are ineffective. The role of endoscopists, pathologists, and patients are investigated. Colorectal cancer is linked to poor compliance with therapy, and attention may be better directed at improving adherence to treatment than strengthening current surveillance programs. Clearly, 5‐ASA compounds, particularly mesalazine, are the most appropriate agents to choose, but there may also be a place for the daily intake of folic acid. Currently, the evidence in support of ursodeoxycholic acid is mixed, and it cannot be recommended, in general, to patients for the prophylaxis of colorectal cancer risk. An alternative approach through better concordance with medications is considered. The situation in Crohn's colitis is less clear. Although the risk of colorectal cancer mirrors that in ulcerative colitis, there are no published community‐based studies that exclusively assess the effects of surveillance on the early detection of cancer, and the benefits of 5‐ASA compounds in treatment seem less certain than in ulcerative colitis. In addition, there have been no assessments of the effects of any medications on cancer risk in Crohn's disease.
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Affiliation(s)
- Affifa Farrukh
- Department of Digestive DiseasesUniversity Hospitals of Leicester NHS Trust Leicester UK
| | - John F Mayberry
- Department of Digestive DiseasesUniversity Hospitals of Leicester NHS Trust Leicester UK
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8
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Anti-Tumor Effects of Vitamin B2, B6 and B9 in Promonocytic Lymphoma Cells. Int J Mol Sci 2019; 20:ijms20153763. [PMID: 31374832 PMCID: PMC6696026 DOI: 10.3390/ijms20153763] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 07/27/2019] [Accepted: 07/30/2019] [Indexed: 12/16/2022] Open
Abstract
Chronic inflammation can lead to tumour initiation and progression. Vitamin B complex has the ability to regulate the immune response and, therefore, inflammation but many of the mechanistic and molecular processes involved in this regulation are still not fully understood. This study sought to determine some of these processes by studying the effects of vitamin B2 (riboflavin) B6 (pyridoxine) and B9 (folic acid) on un-differentiated pro-monocytic lymphoma cells in regard to their ability to alter the proliferation, migration, apoptosis, cytokines and expression levels of programmed death ligand 1. We show that vitamin B2, B6 and B9, on pro-monocytic lymphoma cells exerted an anti-tumorigenic effect. This data could form the basis for future studies in using vitamin B supplementation to reduce cancer cell growth in vivo.
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9
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Chudy-Onwugaje K, Abutaleb A, Buchwald A, Langenberg P, Regueiro M, Schwartz DA, Tracy JK, Ghazi L, Patil SA, Quezada S, Russman K, Horst S, Beaulieu D, Quinn C, Jambaulikar G, Cross RK. Age Modifies the Association Between Depressive Symptoms and Adherence to Self-Testing With Telemedicine in Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24:2648-2654. [PMID: 29846623 PMCID: PMC6262196 DOI: 10.1093/ibd/izy194] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Depression is common in patients with inflammatory bowel disease (IBD) and is known to be associated with poor adherence in the usual care setting. In the last decade, there has been an increase in the use of information technology (IT) for the delivery of IBD care, but the association between depressive symptoms (DS) and adherence to self-testing in this context is not known. We aimed to investigate this association among IBD patients managed via a text messaging-based telemedicine system. METHODS This was a prospective study of participants in the 2 intervention arms of the Telemedicine for Patients with IBD (TELE-IBD) trial. Depressive symptoms were measured at baseline, and then participants received periodic text messages to initiate IBD-specific self-testing. Treatment plans were similarly conveyed, and adherence to self-testing was evaluated at the end of 1 year. Regression analyses were performed, and age-stratified models were constructed to evaluate for effect modification. RESULTS Of the 193 study participants, 48% had DS at baseline. Overall, there was no significant association between DS and adherence to self-testing. However, upon stratification by age, adherence increased with depressive symptoms in those that were 40 years and younger (P = 0.02), but there was no association between depressive symptoms and adherence in the older group (P = 0.53). CONCLUSIONS Younger IBD patients with DS have high adherence when managed in a text messaging-based telemedicine program. Telemedicine interventions have the potential to improve health outcomes in this demographic-a group that is often thought to be difficult to manage due to nonadherence.
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Affiliation(s)
| | - Ameer Abutaleb
- Division of Gastroenterology and Hepatology, Department of Medicine
| | - Andrea Buchwald
- Department of Epidemiology and Public Health, University of Maryland, Baltimore, Maryland
| | - Patricia Langenberg
- Department of Epidemiology and Public Health, University of Maryland, Baltimore, Maryland
| | - Miguel Regueiro
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - David A Schwartz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University, Nashville, Tennessee
| | - J Kathleen Tracy
- Department of Epidemiology and Public Health, University of Maryland, Baltimore, Maryland
| | - Leyla Ghazi
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Seema A Patil
- Division of Gastroenterology and Hepatology, Department of Medicine
| | - Sandra Quezada
- Division of Gastroenterology and Hepatology, Department of Medicine
| | | | - Sara Horst
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University, Nashville, Tennessee
| | - Dawn Beaulieu
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University, Nashville, Tennessee
| | - Charlene Quinn
- Department of Epidemiology and Public Health, University of Maryland, Baltimore, Maryland
| | | | - Raymond K Cross
- Division of Gastroenterology and Hepatology, Department of Medicine,Address correspondence to: Raymond K. Cross, MD, MS, 685 West Baltimore Street, Suite 8-00, Baltimore, MD 21201 ()
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10
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Lopez A, Pouillon L, Beaugerie L, Danese S, Peyrin-Biroulet L. Colorectal cancer prevention in patients with ulcerative colitis. Best Pract Res Clin Gastroenterol 2018; 32-33:103-109. [PMID: 30060933 DOI: 10.1016/j.bpg.2018.05.010] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 05/10/2018] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis is characterized by chronic inflammation, which may lead to the accumulation of high levels of pro-inflammatory cytokines within the colonic mucosa, and thus to dysplastic lesions and cancer. Although the trend is decreasing, ulcerative colitis patients still have a 2.4 fold higher risk of colorectal cancer compared to the general population. The key task is to control colonic inflammation, and a rapid step-up approach while closely monitoring intestinal inflammation are recommented. Surveillance colonoscopy program demonstrated its efficacy for reducing the incidence of colorectal cancer in ulcerative colitis. The impact of medication on the reduction of colorectal cancer risk was hardly investigated and it remains unclear whether they have intrinsic anti-neoplastic properties or only downregulate inflammatory pathways. Several studies showed a decreased risk of colorectal cancer in ulcerative colitis patients treated with 5-aminosalicylic acid and chemoprevention with mesalamine compounds is currently recommended. The current level of evidence is too low for thiopurines and anti-TNFα agents. Large, prospective cohort studies are ongoing and are likely to bring new findings about the impact of drugs on colorectal cancer risk in the current era of biologics.
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Affiliation(s)
- Anthony Lopez
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France.
| | - Lieven Pouillon
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France; Imelda GI Clinical Research Centre, Imeldaziekenhuis Bonheiden, Imeldalaan, Bonheiden, Belgium
| | - Laurent Beaugerie
- Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine, F-75012, France; ERL 1057 INSERM/UMRS 7203, UPMC University, Paris, 06F-75005, Paris, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France
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11
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Qiu X, Ma J, Wang K, Zhang H. Chemopreventive effects of 5-aminosalicylic acid on inflammatory bowel disease-associated colorectal cancer and dysplasia: a systematic review with meta-analysis. Oncotarget 2018; 8:1031-1045. [PMID: 27906680 PMCID: PMC5352032 DOI: 10.18632/oncotarget.13715] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
Background and Aims The chemopreventive effect of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) has been widely studied; however, the results remain conflicting. The aim of this study was to systematically review the literature and update evidence concerning effects of 5-ASA on the risk of colorectal cancer (CRC) and dysplasia (Dys) in patients with ulcerative colitis (UC) or Crohn's disease (CD). Results 5-ASA showed a chemopreventive effect against CRC/Dys in IBD patients (OR = 0.58, 95% CI: 0.45−0.75). However, this effect was significant only in clinical-based studies (OR = 0.51; 95% CI: 0.39−0.65), but not in population-based studies (OR = 0.71; 95% CI: 0.46−1.09). Moreover, this effect was noticeable in patients with UC (OR = 0.46, 95% CI: 0.34−0.61), but not in CD (OR = 0.66, 95% CI: 0.42−1.03), and on the outcome of CRC (OR = 0.54, 95% CI: 0.39−0.74), but not Dys (OR = 0.47; 95% CI: 0.20−1.10). In IBD patients, mesalazine dosage ≥ 1.2 g/day showed greater protective effects against CRC/Dys than dosages < 1.2 g/day. However, Sulphasalazine therapy did not show any noticeable protective function regardless of the dosage administered. Materials and Methods We performed a systematic review with a meta-analysis of 26 observational studies involving 15,460 subjects to evaluate the risks of developing CRC and Dys in IBD patients receiving 5-ASA treatment. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each evaluation index. Conclusions 5-ASA has a chemopreventive effect on CRC (but not Dys) in IBD patients. Moreover, UC patients can benefit more from 5-ASA than CD patients. Mesalazine maintenance dosage ≥ 1.2 g/day is an effective treatment for reducing CRC risk in IBD patients.
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Affiliation(s)
- Xinyun Qiu
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Jingjing Ma
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Kai Wang
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
| | - Hongjie Zhang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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12
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Doherty G, Katsanos KH, Burisch J, Allez M, Papamichael K, Stallmach A, Mao R, Berset IP, Gisbert JP, Sebastian S, Kierkus J, Lopetuso L, Szymanska E, Louis E. European Crohn's and Colitis Organisation Topical Review on Treatment Withdrawal ['Exit Strategies'] in Inflammatory Bowel Disease. J Crohns Colitis 2018; 12:17-31. [PMID: 28981623 DOI: 10.1093/ecco-jcc/jjx101] [Citation(s) in RCA: 131] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 07/31/2017] [Indexed: 12/12/2022]
Abstract
Clinically effective therapies now exist for remission maintenance in both ulcerative colitis [UC] and Crohn's Disease [CD]. For each major class of IBD medications [5-aminosalicyclates, immunomodulators, and biologic agents], used alone or in combination, there is a risk of relapse following reduction or cessation of treatment. A consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the published literature and agreed a series of consensus practice points. The objective of the expert consensus is to provide evidence-based guidance for clinical practice so that physicians can make informed decisions in partnership with their patients. The likelihood of relapse with stopping each class of IBD medication is reviewed. Factors associated with an altered risk of relapse with withdrawal are evaluated, and strategies to monitor and allow early identification of relapse are considered. In general, patients in clinical, biochemical, and endoscopic remission are more likely to remain well when treatments are stopped. Reintroduction of the same treatment is usually, but not always, successful. The decision to stop a treatment needs to be individualized, and shared decision making with the patient should take place.
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Affiliation(s)
- Glen Doherty
- Centre for Colorectal Disease, St Vincent's University Hospital & University College Dublin, Dublin, Ireland
| | - Konstantinos H Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Matthieu Allez
- Department of Gastroenterology and Hepatology, Hôpital Saint-Louis, APHP, INSERM UMRS 1160, Université Denis Diderot, Paris, France
| | | | - Andreas Stallmach
- Department of Internal Medicine IV [Gastroenterology, Hepatology and Infectious Disease], University Hospital Jena, Jena, Germany
| | - Ren Mao
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ingrid Prytz Berset
- Gastroenterology Department, Alesund Hospital, Helse More Romsdal Hospital Trust, Alesund, Norway
| | - Javier P Gisbert
- Department of Gastroenterology, Hospital Universitario de la Princesa, Instituto de Investigaciun Sanitaria Princesa (IIS-IP) and Centro de Investigaciun Biomédica en Red de Enfermedades Heprticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Shaji Sebastian
- IBD Unit, Department of Gastroenterology, Hull & East Yorkshire Hospitals NHS Trust, Hull, UK
| | - Jaroslaw Kierkus
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Children's Memorial Health Institute, Warsaw, Poland
| | - Loris Lopetuso
- Department of Gastroenterology and Internal Medicine, Catholic University of Rome-A. Gemelli Hospital, Rome, Italy
| | - Edyta Szymanska
- Department of Pediatrics, Nutrition, and Metabolic Disorders, Children's Memorial Health Institute, Warsaw, Poland
| | - Edouard Louis
- Department of Gastroenterology, CHU Liège, Sart Tilman, Liège, Belgium
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13
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Martelli L, Lopez A, Strobel S, Danese S, Roblin X, Baumann C, Peyrin-Biroulet L. Adherence to infliximab therapy in inflammatory bowel disease patients in a real-life setting. J Dig Dis 2017; 18:566-573. [PMID: 28858439 DOI: 10.1111/1751-2980.12539] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 07/10/2017] [Accepted: 08/27/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To assess adherence to infliximab (IFX) therapy in inflammatory bowel disease patients, to investigate reasons for non-adherence and to identify predictors for non-adherence. METHODS This observational study was conducted in two French referral university hospitals between 1 September and 31 October, 2011. Patients were systematically asked if they had already delayed or missed an IFX perfusion since the beginning of the treatment and about the reasons for their non-adherence. RESULTS Of the 162 included patients (121 Crohn's disease [CD], 41 ulcerative colitis), 87 (53.7%) reported a delay of at least one IFX injection and 14 (8.6%) missed at least one IFX perfusion since the beginning of the treatment. The overall non-adherence rate was 54.3%. Pooling all misses, the main reasons for non-adherence were pregnancy (33.3%), intentional non-adherence (20%) and forgetfulness (13.3%). Pooling all delays, the main reasons for non-adherence were professional constraints (46.9%), infections (17.3%) and travels (14.3%). Perineal disease was associated with IFX delays (P = 0.0007, odds ratio 4.0), whereas active CD/UC was associated with IFX misses (P = 0.0258, OR = 5.4). CONCLUSIONS The overall non-adherence rate for IFX use was 54.3%. Professional constraints and intentional non-adherence were the leading causes of non-adherence. Perineal disease and active CD were negatively related to adherence.
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Affiliation(s)
- Laura Martelli
- Inserm U954 and Department of Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France
| | - Anthony Lopez
- Inserm U954 and Department of Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France
| | - Sophie Strobel
- Department of Gastroenterology, University Hospital of Saint Etienne, Saint-Etienne, France
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy
| | - Xavier Roblin
- Department of Gastroenterology, University Hospital of Saint Etienne, Saint-Etienne, France
| | - Cédric Baumann
- Clinical Research Support Facility PARC, Nancy University Hospital, Nancy, France
| | - Laurent Peyrin-Biroulet
- Inserm U954 and Department of Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France
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14
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Shuhaibar M, O'Morain C. Colorectal Malignancy in a Prospective Irish Inflammatory Bowel Disease Population 15 Years Since Diagnosis: Comparison with the EC-IBD Cohort. Gastroenterol Res Pract 2017; 2017:4946068. [PMID: 29147110 PMCID: PMC5632876 DOI: 10.1155/2017/4946068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 06/18/2017] [Accepted: 08/01/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIM As part of the EC-IBD prospective inception cohort study, we had unique opportunity to follow up our patients since diagnosis in the early 1990s. PATIENTS AND METHODS All patients from the greater Dublin area (n = 192) were followed up from inception between 1991 and 1993 until the 30 September 2009. Patients who developed malignancies were logged electronically with verification of the site and histology. RESULTS Of the initial 192 patients, 133 were included in the 15-year follow-up. Of those, 80 (60.2%) had UC and 53 (39.8%) had CD. There were 82 (61.7%) males and 51 (38.3%) females. Six patients had extraintestinal malignancy; however, there was no CRC related to IBD noted in our cohort. Four of the 6 identified cases had UC (64%) with a mean age of 54.25 years at the time of cancer diagnosis, whereas the two CD patients had a mean age of 51.5 years at the time of cancer diagnosis. CONCLUSION CRC was not observed in our cohort. The six extraintestinal malignancies did not show significant relation to IBD. The high total colectomy rate (in the prebiological therapy era) may have contributed to low malignancy rate.
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Affiliation(s)
- Mary Shuhaibar
- Department of Gastroenterology/General Medicine, Adelaide and Meath Hospital Incorporating the National Children Hospital, Tallaght, Ireland
- Department of Clinical Medicine, Trinity College Dublin, Dublin 2, Ireland
| | - Colm O'Morain
- Department of Gastroenterology/General Medicine, Adelaide and Meath Hospital Incorporating the National Children Hospital, Tallaght, Ireland
- Department of Clinical Medicine, Trinity College Dublin, Dublin 2, Ireland
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15
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Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis 2017; 11:649-670. [PMID: 28158501 DOI: 10.1093/ecco-jcc/jjx008] [Citation(s) in RCA: 1242] [Impact Index Per Article: 155.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 02/01/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Fernando Magro
- Department of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal
| | | | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Sandro Ardizzone
- Gastrointestinal Unit ASST Fatebenefratelli Sacco-University of Milan-Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita' Cattolica del Sacro Cuore, Rome, Italy
| | - Manuel Barreiro-de Acosta
- Department of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Krisztina B Gecse
- First Department of Medicine, Semmelweis University, Budapest,Hungary
| | | | - Pieter Hindryckx
- Department of Gastroenterology, University Hospital of Ghent, Ghent, Belgium
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK
| | - Gianluca Pellino
- Unit of General Surgery, Second University of Naples,Napoli, Italy
| | - Edyta Zagórowicz
- Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge,UK
| | - Marcus Harbord
- Imperial College London; Chelsea and Westminster Hospital, London,UK
| | - Florian Rieder
- Department of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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16
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Bonovas S, Fiorino G, Lytras T, Nikolopoulos G, Peyrin-Biroulet L, Danese S. Systematic review with meta-analysis: use of 5-aminosalicylates and risk of colorectal neoplasia in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2017; 45:1179-1192. [PMID: 28261835 DOI: 10.1111/apt.14023] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 01/12/2017] [Accepted: 02/12/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND The relationship of 5-aminosalicylates' use with the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD) has been the focus of a growing body of research. AIM To investigate this association through an updated meta-analysis of observational studies. METHODS PubMed, Scopus and major conference proceedings were searched up to December 2016. The identified studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates were calculated using random-effect models. Detailed subgroup analyses were performed. The GRADE approach was used to assess the quality of evidence. RESULTS Thirty-one independent observational studies including 2137 cases of colorectal neoplasia (of which 76% were cancers) were incorporated. Between-study heterogeneity was moderate, while strong suspicion of small-study effects was raised. The overall analysis revealed a protective association between 5-aminosalicylates' use and colorectal neoplasia (RR = 0.57, 95% CI: 0.45-0.71). When the analysis was stratified according to study design and setting, the association was significant in cohort (RR = 0.65, 95% CI: 0.43-0.99; n = 10) and case-control studies (RR = 0.53, 95% CI: 0.40-0.70; n = 21), population-based (RR = 0.70, 95% CI: 0.52-0.94; n = 12) and hospital-based studies (RR = 0.46, 95% CI: 0.34-0.61; n = 19). Exposure to 5-aminosalicylates was protective against cancer (RR = 0.58, 95% CI: 0.45-0.74) and dysplasia (RR = 0.54, 95% CI: 0.35-0.84). The reduction in colorectal neoplasia risk was strong in ulcerative colitis (RR = 0.50, 95% CI: 0.38-0.64), but nonsignificant in Crohn's disease (RR = 0.76, 95% CI: 0.43-1.33). Mesalazine (mesalamine) use was protective (RR = 0.70, 95% CI: 0.51-0.94) with evidence of a dose-effect. The effect of sulfasalazine was marginally nonsignificant (RR = 0.72, 95% CI: 0.51-1.01). CONCLUSIONS Our findings support a potential chemopreventive role of 5-aminosalicylates in IBD. Further, high-quality prospective research is warranted.
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Affiliation(s)
- S Bonovas
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy
| | - G Fiorino
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy
| | - T Lytras
- Hellenic Center for Disease Control and Prevention, Athens, Greece.,Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.,Barcelona Institute for Global Health, Barcelona, Spain
| | | | - L Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - S Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
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17
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Abstract
Now clear evidences are available to support the hypothesis that inflammation accelerates the conditions including events and molecules that reach to various types of cancers. Inflammation is a normal response to infection containing the innate and adaptive immune systems. However, when allowed to continue, unresolved, perturbation of cellular microenvironment takes place; therefore, it leads to adaptations in genes that are linked to cancer. In addition, a lot of data are accessible confirming the concept that tumour microenvironment is orchestrated by various inflammatory cells and goes to neoplastic process and finally invasion, migration and metastasis. However, infiltrations of leucocytes lead to angiogenesis, propagation and invasion. An inflammatory microenvironment that perhaps fostering impact of angiogenesis include cytokines, chemokines, enzymes and growth factors that play key role for expansion and invasion of cancer cells. This insight highlights the pathogenesis of inflammation-associated cancers and also touches and fosters the role of acetamides for the treatment and chemoprevention of carcinomas that are allied with inflammation.
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Affiliation(s)
- Priyanka Rani
- a Department of Chemistry , School of Sciences, IFTM University Moradabad , Uttar Pradesh , India
| | - Dilipkumar Pal
- b Department of Pharmaceutical Sciences , Guru Ghasidas Vishwavidyalaya (A Central University) , Koni, Bilaspur , CG , India
| | - Rahul Rama Hegde
- c Department of Pharmaceutics , School of Pharmaceutical Sciences, IFTM University Moradabad , Uttar Pradesh , India
| | - Syed Riaz Hashim
- d Department of Chemistry , School of Pharmaceutical Sciences, IFTM University Moradabad , Uttar Pradesh , India
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18
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Lenti MV, Selinger CP. Medication non-adherence in adult patients affected by inflammatory bowel disease: a critical review and update of the determining factors, consequences and possible interventions. Expert Rev Gastroenterol Hepatol 2017; 11:215-226. [PMID: 28099821 DOI: 10.1080/17474124.2017.1284587] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Achieving adherence to medications can be a serious challenge for patients affected by inflammatory bowel disease (IBD). Medical treatment is fundamental for inducing and maintaining remission, preventing flares and reducing the risk of colorectal cancer. Non-adherence may affect patients' quality of life resulting in unfavourable treatment outcomes, more hospitalizations and higher healthcare-related costs. Recognising and improving adherence is therefore a primary aim for the treatment of IBD. Areas covered: We critically discuss the current knowledge on medication non-adherence in adult patients affected by IBD, also mentioning a few issues concerning the paediatric and adolescent populations. In particular, we reviewed the literature focusing on the definition and detection of non-adherence, on its extent and on the possible non-modifiable and modifiable factors involved (patient-centred, therapy-related, disease-related and physician-related). Furthermore, we analysed the interventional studies performed so far. The literature review was conducted through PubMed addressing medication non-adherence in IBD, using the keywords 'adherence' and related terms and 'IBD, ulcerative colitis or Crohn's disease'. Expert commentary: Adherence to therapy for IBD is a complex yet fundamental issue that cannot be solved by addressing a single aspect only. Future studies should focus on patient-tailored and multidimensional interventions.
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Affiliation(s)
- Marco Vincenzo Lenti
- a First Department of Internal Medicine , San Matteo Hospital Foundation; University of Pavia , Pavia , Italy.,b Department of Gastroenterology , Leeds Teaching Hospitals NHS Trust, University of Leeds , Leeds , UK
| | - Christian P Selinger
- b Department of Gastroenterology , Leeds Teaching Hospitals NHS Trust, University of Leeds , Leeds , UK
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19
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Soobraty A, Boughdady S, Selinger CP. Current practice and clinicians’ perception of medication non-adherence in patients with inflammatory bowel disease: A survey of 98 clinicians. World J Gastrointest Pharmacol Ther 2017; 8:67-73. [PMID: 28217376 PMCID: PMC5292608 DOI: 10.4292/wjgpt.v8.i1.67] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 11/24/2016] [Accepted: 01/03/2017] [Indexed: 02/06/2023] Open
Abstract
AIM The survey ascertains perceptions and describes current practice of clinicians regarding medication non-adherence in patients with Inflammatory Bowel Disease.
METHODS Gastroenterologists, trainees and inflammatory bowel disease (IBD) specialist nurses from the United Kingdom were invited to a web based survey collecting data on clinician demographics, patient volume and level of interest in IBD. Respondents were asked to estimate non-adherence levels and report use of screening tools and interventions to improve adherence.
RESULTS Non-adherence was seen as an infrequent problem by 57% of 98 respondents. Levels of non-adherence were estimated lower than evidence suggests by 29% for mesalazine (5ASA), 26% for immunomodulators (IMM) and 21% for biologics (BIOL). Respondents reporting non-adherence as a frequent problem were more likely to report adherence levels in line with evidence (5ASA P < 0.001; IMM P = 0.012; BIOL P = 0.015). While 80% regarded screening as important only 25% screen regularly (40% of these with validated assessment tools). Respondents stated forgetfulness, beliefs about necessity of medication and not immediately apparent benefits as the main reasons for non-adherence. Patient counselling on benefits and risks of medication was a commonly used intervention.
CONCLUSION Clinicians treating IBD patients frequently underestimate non-adherence and use of validated screening tools is infrequent. Most respondents identified the main factors associated with non-adherence in line with evidence and often counselled patients accordingly. Professional education should focus more on non-adherence practice to avoid adverse treatment outcomes associated with non-adherence.
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20
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Abstract
Medication adherence is an important challenge while treating chronic illnesses, such as ulcerative colitis (UC), that require a long-term management to induce and maintain clinical remission. This review provides an overview of the role that medication adherence plays in the routine management of UC, with a focus on the results of a recent Italian study reporting the perception of patients with UC regarding adherence to treatment. A literature analysis was conducted on topics, such as measurement of adherence in real practice, causes, risk factors and consequences of non-adherence and strategies, to raise patients' adherence. Most of the data refer to adherence to 5-aminosalicylic acid, and standard of care for the induction and maintenance of remission in UC. The adherence rate to 5-aminosalicylic acid is low in clinical practice, thus resulting in fivefold higher risk of relapse, likely increased risk of colorectal cancer, reduced quality of life and higher health care costs for in- and outpatient settings. There are various causes affecting non-adherence to therapy: forgetfulness, high cost of drugs, lack of understanding of the drug regimen - which are sometimes due to insufficient explanation by the specialist - anxiety created by possible adverse events, lack of confidence in physicians' judgment and complex dosing regimen. The last aspect negatively influences adherence to medication both in clinical trial settings and in real-world practice. Regarding this feature, mesalamine in once-daily dosage may be preferable to medications with multiple doses per day because the simplification of treatment regimens improves adherence.
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Affiliation(s)
- Anna Testa
- Gastroenterology, University of Naples Federico II, Naples
- Correspondence: Anna Testa, Gastroenterology, University of Naples Federico II, Via Sergio Pansini, 5, 80131 Naples, Italy, Email
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21
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Pedersen BK. State of the Art Reviews: Health Benefits Related to Exercise in Patients With Chronic Low-Grade Systemic Inflammation. Am J Lifestyle Med 2016. [DOI: 10.1177/1559827607301410.] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Today, there is substantial evidence to suggest that regular exercise has health-promoting effects, which are beyond its effect on weight control. Regular exercise offers protection against all-cause mortality, and there is evidence from randomized intervention studies that physical training is effective as a treatment in patients with chronic heart diseases, type 2 diabetes, and symptoms related with the metabolic syndrome. Chronic diseases such as cardiovascular disease and type 2 diabetes are associated with chronic low-grade systemic inflammation. This review focuses on the anti-inflammatory effects of exercise that are mediated by muscle-derived cytokines (myokines). It is suggested that myokines may be involved in mediating the health-beneficial effects of exercise and that these in particular are involved in the protection against chronic diseases associated with low-grade inflammation.
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22
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Ananthakrishnan AN, Cagan A, Cai T, Gainer VS, Shaw SY, Churchill S, Karlson EW, Murphy SN, Liao KP, Kohane I. Statin Use Is Associated With Reduced Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2016; 14:973-9. [PMID: 26905907 PMCID: PMC4912917 DOI: 10.1016/j.cgh.2016.02.017] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 02/01/2016] [Accepted: 02/10/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are associated with an increased risk of colorectal cancer (CRC). Chemopreventive strategies have produced weak or inconsistent results. Statins have been associated inversely with sporadic CRC. We examined their role as chemopreventive agents in patients with IBD. METHODS We collected data from 11,001 patients with IBD receiving care at hospitals in the Greater Boston metropolitan area from 1998 through 2010. Diagnoses of CRC were determined using validated International Classification of Diseases, 9th revision, Clinical Modification codes. Statin use before diagnosis was assessed through analysis of electronic prescriptions. We performed multivariate logistic regression analyses, adjusting for potential confounders including primary sclerosing cholangitis, smoking, increased levels of inflammation markers, and CRC screening practices to identify an independent association between statin use and CRC. We performed sensitivity analyses using propensity score adjustment and variation in the definition of statin use. RESULTS In our cohort, 1376 of the patients (12.5%) received 1 or more prescriptions for a statin. Patients using statins were more likely to be older, male, white, smokers, and have greater comorbidity than nonusers. Over a follow-up period of 9 years, 2% of statin users developed CRC compared with 3% of nonusers (age-adjusted odds ratio, 0.35; 95% confidence interval, 0.24-0.53). On multivariate analysis, statin use remained independently and inversely associated with CRC (odds ratio, 0.42; 95% confidence interval, 0.28-0.62). Our findings were robust on a variety of sensitivity and subgroup analyses. CONCLUSIONS Statin use was associated inversely with the risk of CRC in a large IBD cohort. Prospective studies on the role of statins as chemopreventive agents are warranted.
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Affiliation(s)
- Ashwin N. Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA,Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Andrew Cagan
- Research IS and Computing, Partners HealthCare, Charlestown, MA
| | - Tianxi Cai
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
| | | | - Stanley Y Shaw
- Harvard Medical School, Boston, MA,Department of Medicine, Massachusetts General Hospital, Boston, MA,Center for Systems Biology, Massachusetts General Hospital, Boston, MA
| | | | - Elizabeth W. Karlson
- Harvard Medical School, Boston, MA,Division of Rheumatology, Allergy and Immunology, Brigham and Women’s Hospital, Boston, MA
| | - Shawn N. Murphy
- Harvard Medical School, Boston, MA,Department of Neurology, Massachusetts General Hospital, Boston, MA
| | - Katherine P. Liao
- Harvard Medical School, Boston, MA,Division of Rheumatology, Allergy and Immunology, Brigham and Women’s Hospital, Boston, MA
| | - Isaac Kohane
- Harvard Medical School, Boston, MA,Department of Biomedical Informatics, Harvard Medical School,Children’s Hospital Boston, Boston, MA
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23
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Abstract
BACKGROUND Rectal mesalamine is an effective induction and maintenance therapy for ulcerative colitis. Little is known about the adherence rates to rectal mesalamine or barriers to its use. The aim was to quantify the prevalence of nonadherence to rectal mesalamine and to identify patient-reported barriers to adherence. METHODS A cohort of patients with ulcerative colitis was prospectively enrolled in this observational study and followed for 12 months. Adherence was assessed by tracking pharmacy refills (medication possession ratio). Individual interviews were undertaken in a subset of subjects. Transcripts from the focus groups and interviews were analyzed to identify themes and links between these themes using qualitative data software (MaxQDA). RESULTS Seventy patients prescribed rectal mesalamine were prospectively enrolled in the study. At enrollment, 39 of 70 subjects (55%) self-reported "occasional nonadherence" to rectal mesalamine. Over the 12-month follow-up period, only 20 subjects (26%) completed 3 or more refills. Males, or subjects prescribed a once-a-day suppository, were significantly more likely to refill than females (odds ratio = 3.3, 95% confidence interval, 1.1-10.9) or those prescribed suppositories more than once a day (odds ratio = 1.3, 95% confidence interval, 1.1-1.7). By medication possession ratio criteria, 71% of all subjects were nonadherent with their prescribed regimen (medication possession ratio <0.6). Nonadherers were significantly older than adherent subjects: mean age 48 years in nonadherers, versus 37 in adherers, P = 0.04. Patients who were nonadherent to rectal mesalamine frequently cited the mode of administration (65%) and busy lifestyle (40%) as reasons for nonadherence. CONCLUSIONS Intentional nonadherence is common in patients who have been prescribed rectal mesalamine. Gender, age, frequency of dosing, and lifestyle factors may impact adherence.
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24
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Mesalamine, but Not Sulfasalazine, Reduces the Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: An Agent-specific Systematic Review and Meta-analysis. Inflamm Bowel Dis 2015; 21:2562-9. [PMID: 26296062 DOI: 10.1097/mib.0000000000000540] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only mesalamine at doses greater than 1.2 g per day is currently widely in this setting. The specific impact of mesalamine at these doses has not has not previously been determined. METHODS We performed a systematic review and meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN) from prior cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. A quality assessment was made of all included studies. RESULTS Mesalamine was associated with a modest reduction in the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4-0.9, P = 0.04). This effect was only noted in hospital-based studies and only in the reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3-0.9, P = 0.02) than lower doses. This effect was also only present in the hospital-based studies. In contrast, there was no reduction in the risk of CRN in patients prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5-1.2, P = 0.3), regardless of study setting. CONCLUSIONS Mesalamine, particularly at doses >1.2 g per day, produces a modest reduction in the risk of CRN in inflammatory bowel disease patient populations from referral centers. Sulfasalazine does not seem to reduce the risk. No benefit was noted in population-based studies.
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25
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Yu X, Lian B, Wang L, Zhang Y, Dai E, Meng F, Liu D, Wang S, Liu X, Wang J, Li X, Jiang W. The pan-cancer analysis of gene expression patterns in the context of inflammation. MOLECULAR BIOSYSTEMS 2015; 10:2270-6. [PMID: 24958091 DOI: 10.1039/c4mb00258j] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Although several studies have investigated the essential roles of inflammation in tumor progression, not many have systematically analyzed gene expression patterns across diverse cancers in the context of inflammation. In this study, in order to better understand the inflammatory scenario, we initially constructed the inflammatory timeline (IT) based on two gene expression profiles during inflammatory progression (inflammatory bowel disease and Helicobacter pylori infection). Then, we separately identified the differentially expressed genes (DEGs) from 25 cancer-related microarray data. By comparing the distributions of DEGs in the IT, we identified three novel pan-cancer gene expression patterns. In the first pattern, the up-regulated genes in cancers were over-expressed in the early phase of inflammation, while the down-regulated genes were over-expressed in the late phase of inflammation. The second pattern was the opposite of the first one. The third pattern appeared to be transitional between the first and second patterns. We found that some cancers with different tissue origins have similar gene expression patterns. Finally, we identified two sets of tissue-independent inflammatory signatures that were over-expressed in early and late phases of inflammation, respectively. The dominant biological processes of early inflammatory signatures were cell proliferation, DNA replication, and DNA repair, whereas the late inflammatory signatures were reflective of innate immune response, neutrophil migration, and antigen processing. These inflammatory signatures may be useful to predict gene expression patterns in human cancers. Therefore, the pan-cancer analysis of gene expression patterns in the context of inflammation provides a novel insight into cancers and an unprecedented opportunity to develop new therapies.
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Affiliation(s)
- Xuexin Yu
- College of Bioinformatics Science and Technology, Harbin Medical University, China.
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Xc- inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism. Cancer Lett 2015; 368:88-96. [PMID: 26254540 DOI: 10.1016/j.canlet.2015.07.031] [Citation(s) in RCA: 132] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 07/22/2015] [Accepted: 07/26/2015] [Indexed: 01/17/2023]
Abstract
Sulfasalazine (SSZ) is an anti-inflammatory drug that has been demonstrated to induce apoptosis and tumor regression through inhibition of plasma membrane cystine transporter xc(-). Cysteine is a rate-limiting precursor for intracellular glutathione (GSH) synthesis, which is vital for compound detoxification and maintaining redox balance. Platinum-based chemotherapy is an important regimen used in clinics for various cancers including colorectal cancer (CRC). We hypothesized that targeting xc(-) transporter by SSZ may annihilate cellular detoxification through interruption of GSH synthesis and may enhance the anti-cancer activity of cisplatin (CDDP) by increasing drug transport. In the present study, we revealed that xCT, the active subunit of xc(-), is highly expressed in CRC cell lines and human colorectal carcinoma tissues compared with their normal counterparts. SSZ effectively depleted cellular GSH, leading to significant accumulation of reactive oxygen species and growth inhibition in CRC cells. In contrast, the normal epithelial cells of colon origin were less sensitive to SSZ, showing a moderate ROS elevation. Importantly, SSZ effectively enhanced the intracellular platinum level and cytotoxicity of CDDP in CRC cells. The synergistic effect of SSZ and CDDP was reversed by antioxidant N-acetyl-L-cysteine (NAC). Together, these results suggest that SSZ, a relatively non-toxic drug that targets cystine transporter, may, in combination with CDDP, have effective therapy for colorectal cancer.
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27
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Prabhakar N, Kalra N, Bhasin DK, Rana SS, Gupta V, Singh R, Khandelwal N. Comparison of CT colonography with conventional colonoscopy in patients with ulcerative colitis. Acad Radiol 2015; 22:296-302. [PMID: 25435187 DOI: 10.1016/j.acra.2014.09.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 09/21/2014] [Accepted: 09/26/2014] [Indexed: 02/01/2023]
Abstract
RATIONALE AND OBJECTIVE Patients with ulcerative colitis require recurrent conventional colonoscopy (CC) to define the extent of the disease. Computed tomography (CT) colonography (CTC) can be used as an alternative technique for studying the colon in these patients. The purpose of the study was to compare the findings of CTC to CC in patients with ulcerative colitis. MATERIALS AND METHODS Twenty patients proven to have ulcerative colitis on biopsy and in clinical remission state were enrolled in the study. They underwent CTC and CC within 1 week of each test. The investigators performing CTC and CC were blinded to the findings of each other. The chi-square test, kappa test, sensitivity, and specificity were used to compare the findings on CTC and CC. In addition, patient acceptance for both the procedures was compared. RESULTS Sensitivity and specificity on CTC for detecting granular appearance were 81.0% and 73.8%, respectively, and for pseudopolyps were 82.1% and 84.5%, respectively. Good correlation was seen between CTC and CC for detection of granular appearance and pseudopolyps. Loss of haustral folds, wall thickening, pericolonic vascularity, and pericolonic lymph nodes seen on CTC were found to correlate with intraluminal findings seen on CC. Patient acceptance for CTC was better than that for CC. CONCLUSIONS CTC can be used for evaluating patients with ulcerative colitis who are in remission.
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Affiliation(s)
- Nidhi Prabhakar
- Department of Radiodiagnosis, PGIMER, Chandigarh 160012, India
| | - Naveen Kalra
- Department of Radiodiagnosis, PGIMER, Chandigarh 160012, India.
| | | | | | - Vikas Gupta
- Department of General Surgery, PGIMER, Chandigarh, India
| | - Rajinder Singh
- Department of General Surgery, PGIMER, Chandigarh, India
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Park E, Park MH, Na HS, Chung J. Xylitol induces cell death in lung cancer A549 cells by autophagy. Biotechnol Lett 2015; 37:983-90. [PMID: 25650339 DOI: 10.1007/s10529-014-1757-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 12/18/2014] [Indexed: 12/30/2022]
Abstract
Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.
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Affiliation(s)
- Eunjoo Park
- Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan-si, 626-870, Gyeongsangnam-do, South Korea
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van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. [Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 3: Special situations (Spanish version)]. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2015; 80:74-106. [PMID: 25769216 DOI: 10.1016/j.rgmx.2014.10.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 10/23/2014] [Indexed: 12/12/2022]
Affiliation(s)
- G van Assche
- En nombre de la ECCO; G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
| | - A Dignass
- G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
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30
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Klotz C, Barret M, Dhooge M, Oudjit A, Chaussade S, Coriat R, Abitbol V. [Management of diagnosis and treatment in ulcerative colitis]. Presse Med 2014; 44:144-9. [PMID: 25534469 DOI: 10.1016/j.lpm.2014.06.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Revised: 05/23/2014] [Accepted: 06/03/2014] [Indexed: 02/07/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease limited to the mucosa and affecting the rectum and the colon continuously. Salicylates are the first line treatment for moderate forms. Corticosteroids are used to induce remission, but are not given as maintenance therapy. Thiopurines are indicated as maintenance therapy in case of failure of salicylates or cortico-dependence. Anti TNF alpha are indicated in cortico-resistant severe flares or if cortico- dependence. Vedolizumab (anti-integrin) is the first non anti-TNF alpha biotherapy available for the treatment of UC. Severe acute colitis is a medical emergency; diagnosis is based on Lichtiger score. An emergency colectomy for severe acute colitis is indicated in cases of surgical complication or resistance to medical therapy. UC patients with extension beyond splenic flexure are at risk of colorectal cancer, increasing with the duration of the disease, severity of mucosal inflammation, family history of colorectal cancer, and the existence of sclerosing cholangitis. Annual surveillance colonoscopy is required in patients with sclerosing cholangitis regardless of the extension of their UC.
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Affiliation(s)
- Caroline Klotz
- AP-HP, hôpital Cochin, service de gastroentérologie, 75014 Paris, France
| | - Maximilien Barret
- AP-HP, hôpital Cochin, service de gastroentérologie, 75014 Paris, France; Université Sorbonne Paris Descartes, faculté de médecine, 75014 Paris, France
| | - Marion Dhooge
- AP-HP, hôpital Cochin, service de gastroentérologie, 75014 Paris, France; Université Sorbonne Paris Descartes, faculté de médecine, 75014 Paris, France
| | - Ammar Oudjit
- AP-HP, hôpital Cochin, service de radiologie, 75014 Paris, France
| | - Stanislas Chaussade
- AP-HP, hôpital Cochin, service de gastroentérologie, 75014 Paris, France; Université Sorbonne Paris Descartes, faculté de médecine, 75014 Paris, France
| | - Romain Coriat
- AP-HP, hôpital Cochin, service de gastroentérologie, 75014 Paris, France; Université Sorbonne Paris Descartes, faculté de médecine, 75014 Paris, France
| | - Vered Abitbol
- AP-HP, hôpital Cochin, service de gastroentérologie, 75014 Paris, France.
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Moss AC, Lillis Y, Edwards George JB, Choudhry NK, Berg AH, Cheifetz AS, Horowitz G, Leffler DA. Attitudes to mesalamine questionnaire: a novel tool to predict mesalamine nonadherence in patients with IBD. Am J Gastroenterol 2014; 109:1850-5. [PMID: 24913040 DOI: 10.1038/ajg.2014.158] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 04/14/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Poor adherence to mesalamine is common and driven by a combination of lifestyle and behavioral factors, as well as health beliefs. We sought to develop a valid tool to identify barriers to patient adherence and predict those at risk for future nonadherence. METHODS A 10-item survey was developed from patient-reported barriers to adherence. The survey was administered to 106 patients with ulcerative colitis who were prescribed mesalamine, and correlated with prospectively collected 12-month pharmacy refills (medication possession ratio (MPR)), urine levels of salicylates, and self-reported adherence (Morisky Medication Adherence Scale (MMAS)-8). RESULTS From the initial 10-item survey, 8 items correlated highly with the MMAS-8 score at enrollment. Computer-generated randomization produced a derivation cohort of 60 subjects and a validation cohort of 46 subjects to assess the survey items in their ability to predict future adherence. Two items from the patient survey correlated with objective measures of long-term adherence: their belief in the importance of maintenance mesalamine even when in remission and their concerns about side effects. The additive score based on these two items correlated with 12-month MPR in both the derivation and validation cohorts (P<0.05). Scores on these two items were associated with a higher risk of being nonadherent over the subsequent 12 months (relative risk (RR) =2.2, 95% confidence interval=1.5-3.5, P=0.04). The area under the curve for the performance of this 2-item tool was greater than that of the 10-item MMAS-8 score for predicting MPR scores over 12 months (area under the curve 0.7 vs. 0.5). CONCLUSIONS Patients' beliefs about the need for maintenance mesalamine and their concerns about side effects influence their adherence to mesalamine over time. These concerns could easily be raised in practice to identify patients at risk of nonadherence (Clinical Trial number NCT01349504).
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Affiliation(s)
- Alan C Moss
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Yvonne Lillis
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Jessica B Edwards George
- Northeastern University, Department of Counseling and Applied Educational Psychology, Boston, Massachusetts, USA
| | - Niteesh K Choudhry
- Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Anders H Berg
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Adam S Cheifetz
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Gary Horowitz
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Dan A Leffler
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Bae SI, Kim YS. Colon cancer screening and surveillance in inflammatory bowel disease. Clin Endosc 2014; 47:509-15. [PMID: 25505716 PMCID: PMC4260098 DOI: 10.5946/ce.2014.47.6.509] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Accepted: 08/05/2014] [Indexed: 12/13/2022] Open
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Accordingly, the duration and anatomic extent of the disease have been known to affect the development of IBD-related CRC. When CRC occurs in patients with IBD, unlike in sporadic CRC, it is difficult to detect the lesions because of mucosal changes caused by inflammation. In addition, the tumor types vary with ill-circumscribed lesions, and the cancer is difficult to diagnose and remedy at an early stage. For the diagnosis of CRC in patients with IBD, screening endoscopy is recommended 8 to 10 years after the IBD diagnosis, and surveillance colonoscopy is recommended every 1 to 2 years thereafter. The recent development of targeted biopsies using chromoendoscopy and relatively newer endoscopic techniques helps in the early diagnosis of CRC in patients with IBD. A total proctocolectomy is advisable when high-grade dysplasia or multifocal low-grade dysplasia is confirmed by screening endoscopy or surveillance colonoscopy or if a nonadenoma-like dysplasia-associated lesion or mass is detected. Currently, pharmacotherapies are being extensively studied as a way to prevent IBD-related CRC.
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Affiliation(s)
- Song I Bae
- Department of Internal Medicine, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - You Sun Kim
- Department of Internal Medicine, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
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33
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Zhao LN, Li JY, Yu T, Chen GC, Yuan YH, Chen QK. 5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis. PLoS One 2014; 9:e94208. [PMID: 24710620 PMCID: PMC3978022 DOI: 10.1371/journal.pone.0094208] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2013] [Accepted: 03/13/2014] [Indexed: 12/20/2022] Open
Abstract
Background Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Methods Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Results Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89]. Conclusion Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.
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Affiliation(s)
- Li-Na Zhao
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China
| | - Jie-Yao Li
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China
| | - Tao Yu
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China
- * E-mail:
| | - Guang-Cheng Chen
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China
| | - Yu-Hong Yuan
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China
| | - Qi-Kui Chen
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China
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Selinger CP, Kemp A, Leong RW. Persistence to oral 5-aminosalicylate therapy for inflammatory bowel disease in Australia. Expert Rev Gastroenterol Hepatol 2014; 8:329-34. [PMID: 24490626 DOI: 10.1586/17474124.2014.882768] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Aminosalicylate (5-ASA) is effective treatment for inflammatory bowel diseases (IBDs) but requires continuous maintenance therapy. This study determines persistence of 5-ASA in IBD using national population-based data for Australia from 2002 to 2011 with follow up for 36 months. Non-persistence was defined as failing to fill a prescription for 3 months. Of 12,592 patients those initiated on non-sulphasalazine 5-ASA (2917) had significantly higher persistence (P < 0.001) than those on sulphasalazine (9675). Persistence for sulphasalazine and non-sulphasalazine 5-ASA initiation was 22.3% and 28.5% at 12-months, and 11.9% and 16.2% at 24-months. Sulphasalazine poor persistence continued despite intra-class switch to another 5-ASA. Patients receiving immunomodulator co-therapy had higher persistence (P < 0.001). National population-based data identified persistence to 5-ASA to be low but significantly lower when sulphasalazine is the initial drug. Physicians should stress the importance of long-term 5-ASA therapy as overall drug efficacy especially the 5-ASA chemo-prophylactic benefits may be reduced by non-persistence.
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Affiliation(s)
- Christian P Selinger
- Gastroenterology and Liver Services, Concord Hospital and Bankstown Hospital, Sydney, Australia
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Sebastian S, Hernández V, Myrelid P, Kariv R, Tsianos E, Toruner M, Marti-Gallostra M, Spinelli A, van der Meulen-de Jong AE, Yuksel ES, Gasche C, Ardizzone S, Danese S. Colorectal cancer in inflammatory bowel disease: results of the 3rd ECCO pathogenesis scientific workshop (I). J Crohns Colitis 2014; 8:5-18. [PMID: 23664897 DOI: 10.1016/j.crohns.2013.04.008] [Citation(s) in RCA: 94] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2013] [Accepted: 04/05/2013] [Indexed: 02/08/2023]
Abstract
Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop.
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Affiliation(s)
- Shaji Sebastian
- Hull & East Yorkshire Hospitals NHS Trust, Hull York Medical School, Hull, United Kingdom.
| | - Vincent Hernández
- Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Pär Myrelid
- Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, County Council of Östergötland, Linköping, Sweden
| | - Revital Kariv
- Service for Gastrointestinal Malignancies, Department of Gastroenterology & Liver Disease, Tel Aviv Sourasky Medical Center, Israel
| | - Epameinondas Tsianos
- University of Ioannina, 1st Division of Internal Medicine and Hepato-Gastroenterology Unit, Greece
| | - Murat Toruner
- Ankara University Medical School, Ibni Sina Hospital, Division of Gastroenterology, Ankara, Turkey
| | - Marc Marti-Gallostra
- Department of Colorectal Surgery, University Hospital of Valle de Hebron, Barcelona, Spain
| | - Antonino Spinelli
- Dipartimento e Cattedra di Chirurgia Generale, Istituto Clinico Humanitas IRCCS, Università degli Studi di Milano, Rozzano, Milano, Italy
| | | | - Elif Sarıtas Yuksel
- Department of Gastroenterology, Katip Celebi University, Ataturk Research and Teaching Hospital, Izmir, Turkey
| | - Christoph Gasche
- Christian Doppler Laboratory on Molecular Cancer Chemoprevention, Division of Gastroenterology, Medical University of Vienna, Vienna, Austria
| | - Sandro Ardizzone
- Chair of Gastroenterology, "L. Sacco" University Hospital, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy.
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Gómez-García M, Cabello-Tapia MJ, Sánchez-Capilla AD, Teresa-Galván JD, Redondo-Cerezo E. Thiopurines related malignancies in inflammatory bowel disease: Local experience in Granada, Spain. World J Gastroenterol 2013; 19:4877-86. [PMID: 23946592 PMCID: PMC3740417 DOI: 10.3748/wjg.v19.i30.4877] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Revised: 08/25/2012] [Accepted: 09/12/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the incidence of neoplasms in inflammatory bowel disease (IBD) patients and the potential causative role of thiopurines.
METHODS: We performed an observational descriptive study comparing the incidence of malignancies in IBD patients treated with thiopurines and patients not treated with these drugs. We included 812 patients which were divided in two groups depending on whether they have received thiopurines or not. We have studied basal characteristics of both groups (age when the disease was diagnosed, sex, type of IBD, etc.) and treatments received (Azathioprine, mercaptopurine, infliximab, adalimumab or other immunomodulators), as well as neoplasms incidence. Univariate analysis was performed with the student t test, χ2 test or Wilcoxon exact test as appropriate. A logistic regression analysis was performed as multivariate analysis. Statistical significance was establish at P values of less than 0.05, and 95%CI were used for the odds ratios.
RESULTS: Among 812 patients included, 429 (52.83%) have received thiopurines: 79.5% azathioprine, 14% mercaptopurine and 6.5% both drugs. 44.76% of patients treated with thiopurines and 46, 48% of patients who did not receive this treatment were women (P > 0.05). The proportion of ulcerative colitis patients treated with thiopurines was 30.3% compare to 66. 67% of patients not treated (P < 0.001). Mean azathioprine dose was 123.79 ± 36.5 mg/d (range: 50-250 mg/d), mean usage time was 72.16 ± 55.7 mo (range: 1-300 mo) and the accumulated dose along this time was 274.32 ± 233.5 g (1.5-1350 g). With respect to mercaptopurine, mean dose was 74.7 ± 23.9 mg/d (range: 25-150 mg/d), mean usage time of 23.37 ± 27.6 mo (range: 1-118 mo), and the accumulated dose along this time was 52.2 ± 63.5 g (range: 1.5-243 g). Thiopurine S-methyltransferase activity was tested in 66% of patients treated with thiopurines, among which 98.2% had an intermediate or high activity. Among the patients treated with thiopurines, 27.27% (112 patients) and 11.66% (50 patients) received treatment with Infliximab and Adalimumab respectively, but only 1.83% (7 patients) and 0.78% (3 patients) received these drugs in the group of patients who did not received thiopurines (P < 0.001 and P < 0.001 respectively). Finally, 6.8% (29 patients) among those treated with thiopurines have received other immunesupresants (Methotrexate, Tacrolimus, Cyclosporin), compare to 1% (4 patients) of patients not treated with thiopurines (P < 0.001). Among patients treated with thiopurines, 3.97% developed a malignancy, and among those not treated neoplasms presented in 8.1% (P = 0.013). The most frequent neoplasms were colorectal ones (12 cases in patients not treated with thiopurines but none in treated, P < 0.001) followed by non-melanoma skin cancer (8 patients in treated with thiopurines and 6 in not treated, P > 0.05).
CONCLUSION: In our experience, thiopurine therapy did not increase malignancies development in IBD patients, and was an efective and safe treatment for these diseases.
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37
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Van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J Crohns Colitis 2013; 7:1-33. [PMID: 23040453 DOI: 10.1016/j.crohns.2012.09.005] [Citation(s) in RCA: 334] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Accepted: 09/03/2012] [Indexed: 02/07/2023]
Affiliation(s)
- Gert Van Assche
- Division of Gastroenterology, Department of Medicine, Mt. Sinai Hospital and University Health Network,University of Toronto and University of Leuven, 600 University Avenue, Toronto, ON, Canada M5G 1X5.
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38
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Abstract
5-aminosalicylates (5-ASA) are widely used to treat patients with ulcerative colitis. Experimental data suggest that these agents can potentially be used in a chemopreventive fashion to inhibit the development of colitis-associated colorectal cancer (CRC); however, observational studies investigating a possible risk reduction of CRC by 5-ASA therapy have revealed conflicting results. Currently, it appears that 5-ASA have no or only a very limited effect as a deterrence against CRC. Thus, a general recommendation for long-term use of 5-ASA solely for chemopreventive measures is not warranted.
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Affiliation(s)
- Hans Herfarth
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC 27599, USA.
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Khan N, Abbas AM, Bazzano LA, Koleva YN, Krousel-Wood M. Long-term oral mesalazine adherence and the risk of disease flare in ulcerative colitis: nationwide 10-year retrospective cohort from the veterans affairs healthcare system. Aliment Pharmacol Ther 2012; 36:755-64. [PMID: 22882428 DOI: 10.1111/apt.12013] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Revised: 06/21/2012] [Accepted: 07/18/2012] [Indexed: 01/01/2023]
Abstract
BACKGROUND Adherence is a major factor in determining disease activity in ulcerative colitis (UC). There are limited data on long-term nationwide adherence levels among patients with UC. AIM To evaluate the long-term adherence levels to oral mesalazine (mesalamine) in the Veterans Affairs (VA) healthcare system, to determine the impact of non-adherence on the risk of flares, and to evaluate the different pharmacy data-based adherence indicators. METHODS Nationwide data were obtained from the VA for the period 2001-2011. UC patients who started mesalazine maintenance during the inclusion period were included. Level of adherence was assessed using three different indicators: medication possession ratio (MPR), continuous single-interval medication availability (CSA) and continuous multiple-interval medication gaps (CMG). Cox regression modelling was used to predict disease flares and assess the predictive value of each adherence indicator. RESULTS We included 13 062 patients into the analysis with median follow-up time of 6.1 years. Percentage of patients with high adherence was 47%, 43%, 31% as identified by CSA, MPR and CMG respectively. Low adherers had a significant increase in the risk of flares compared with high adherers (Hazard ratio: 2.8, 1.7 and 1.8, P < 0.001 for CSA, MPR and CMG, respectively). Compared with other adherence indicators, CSA offered the best trend in predicting disease flares. CONCLUSIONS Long-term high-adherence level was lower than previously reported. Adherence was a significant factor in predicting disease flares. Pharmacy adherence indicators may be useful to healthcare providers in identifying patients at high risk of exacerbations.
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Affiliation(s)
- N Khan
- Southeast Louisiana Veterans Health Care System, New Orleans, LA, USA.
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40
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Abstract
A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle are key risk factors for colorectal cancer (CRC). Prevention of CRC has long been considered a plausible approach for the population and individuals at high risk for developing this disease. A significant effort has been made in the development of novel drugs for both prevention and treatment over the past two decades. This review highlights recent advances in our understanding of the role of nonsteroidal anti-inflammatory drugs in CRC prevention and adjuvant treatment. Moreover, we focus on the molecular mechanisms underlying the antitumor effects of these drugs in CRC. The knowledge of how anti-inflammatory agents inhibit cancer formation and progression may provide a rationale for the development of more effective chemopreventive and chemotherapeutic agents with less toxicity.
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Affiliation(s)
- Dingzhi Wang
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA
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41
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5-aminosalicylic acid is not protective against colorectal cancer in inflammatory bowel disease: a meta-analysis of non-referral populations. Am J Gastroenterol 2012; 107:1298-304; quiz 1297, 1305. [PMID: 22751467 DOI: 10.1038/ajg.2012.198] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Some studies have demonstrated that 5-aminosalicylic acid (5-ASA) is associated with a reduced risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD). However, more recent population-based studies suggest no protective association. We conducted a systematic review that focused on non-referral studies to reassess the role of 5-ASA for this indication. METHODS We searched MEDLINE, EMBASE, and the Cochrane databases for studies of non-referral populations that assessed the association between 5-ASA use for at least 1 year and colorectal neoplasia between 1966 and 2011 and conducted a quantitative meta-analysis. RESULTS Four observational studies fulfilled inclusion criteria. The pooled adjusted odds ratio (aOR) was 0.95 (95% confidence interval (CI): 0.66-1.38), but there was moderate heterogeneity (I2 = 58.2%; P = 0.07). A sensitivity analysis that included a fifth study in which 5-ASA use was only for a minimum of 3 months yielded a pooled aOR of 0.82 (95% CI: 0.54-1.26). A series of sensitivity analyses in which each of the four studies was excluded one at a time did not show any significant change in the overall pooled OR. We conducted a separate meta-analysis of nine clinic-based studies, which, in contrast, yielded a pooled OR of 0.58 (95% CI: 0.45-0.75). CONCLUSIONS Our meta-analysis yielded inconsistent results that were dependent on the inclusion of either non-referral or clinic-based populations. Based on non-referral studies, there does not seem to be a protective effect of 5-ASA on CRC in IBD. However, heterogeneity among these studies limits their interpretation.
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42
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Herrinton LJ, Liu L, Levin TR, Allison JE, Lewis JD, Velayos F. Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology 2012; 143:382-9. [PMID: 22609382 DOI: 10.1053/j.gastro.2012.04.054] [Citation(s) in RCA: 233] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Revised: 04/16/2012] [Accepted: 04/30/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS The relationship between inflammatory bowel disease (IBD) and the incidence and mortality of colorectal adenocarcinoma (CRC) has not been evaluated recently. METHODS We calculated the incidence and standardized incidence and mortality rate ratios of CRC among adult individuals with intact colons using Kaiser Permanente of Northern California's database of members with IBD and general membership data for the period of 1998 to June 2010 (data through 2008 were used to calculate mortality). We also evaluated trends in medication use and rates of cancer detection over time. RESULTS We identified 29 cancers among persons with Crohn's disease (CD) and 53 among persons with ulcerative colitis (UC). Overall, the incidence rates of cancer among individuals with CD, UC, or in the general membership were 75.0, 76.0, and 47.1, respectively, per 100,000 person-years. In the general population, the incidence of CRC was 21% higher in 2007-2010 than in 1998-2001 (P for trend, <.0001), coincident with the growth of CRC screening programs. The incidence of CRC among individuals with CD or UC was 60% higher than in the general population (95% confidence interval [CI] for CD, 20%-200%; 95% CI for UC, 30%-200%) and was stable over time (P for trend was as follows: CD, .98; UC, .40). During 1998-2008, the standardized mortality ratio for CRC in individuals with CD was 2.3 (95% CI, 1.6-3.0) and 2.0 in those with UC (95% CI, 1.3-2.7). Over the study period, anti-tumor necrosis factor agents replaced other therapies for CD and UC; the rate of colonoscopy increased by 33% among patients with CD and decreased by 9% in those with UC. CONCLUSIONS From 1998 to 2010, the incidence of CRC in patients with IBD was 60% higher than in the general population and essentially stable over time.
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43
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Hodgkins P, Swinburn P, Solomon D, Yen L, Dewilde S, Lloyd A. Patient preferences for first-line oral treatment for mild-to-moderate ulcerative colitis: a discrete-choice experiment. PATIENT-PATIENT CENTERED OUTCOMES RESEARCH 2012; 5:33-44. [PMID: 22077619 DOI: 10.2165/11595390-000000000-00000] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
BACKGROUND Patients with ulcerative colitis (UC) frequently require long-term therapy to prevent relapse. Treatments such as 5-aminosalicylic acid (5-ASA [mesalazine]) are efficacious and well tolerated, but adherence to treatment is often poor. OBJECTIVE This discrete-choice experiment (DCE) was conducted to estimate differences in patient preferences for 5-ASA treatment in mild-to-moderate UC based on levels of self-reported adherence. Inclusion of patients residing in the US, UK, Germany, and Canada allowed for assessment of possible cultural differences in patient preferences. METHODS DCE attributes were determined through literature review, clinician consultation, and patient interviews. Six treatment attributes were identified: ease of swallowing, time of day, quantity, extent of flare resolution, likelihood of flare occurrence, and cost. A total of 400 patients in four countries completed the DCE and adherence (Modified Morisky Scale) surveys. Data were analyzed using generalized estimating equations to estimate patient preference and willingness to pay (WTP) by levels of self-reported adherence and country of residence. RESULTS All attributes had expected polarity and were significant predictors of patient preference. Self-reported 'good' versus 'poor' adherers significantly preferred symptom control (p = 0.0108) and mucosal healing (p = 0.0190) attributes. All patients stated preference for symptom control/mucosal healing and flare risk attributes; the latter attribute was significantly preferred across all countries. Country differences in patient preference for convenience versus clinical attributes were found. Overall, patients were willing to pay £29.24 ($US46.27) per month for symptom control and mucosal healing, and an additional £78.81 ($US124.70) per month for reduction in flare risk to 10% per year (WTP costs were equalized between each country using the published 2008 purchasing power parity). Those with flares in the past year significantly preferred avoiding future flares (p < 0.0001) versus other attributes, as well as lower risk of flares (10%, likelihood ratio: 0.64-0.70). CONCLUSIONS Findings indicate that self-reported adherers to UC therapy have a stronger preference for clinical benefits over other treatment attributes, suggesting that positive patient assessment of effectiveness may influence adherence. Ongoing clinician assessment of patient preferences for treatment attributes, as well as education on the importance of adherence, may help improve treatment outcomes in UC.
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Affiliation(s)
- Paul Hodgkins
- Global Health Economics Outcomes Research, Shire Pharmaceuticals, Wayne, PA, USA.
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44
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Kisiel JB, Loftus EV, Harmsen WS, Zinsmeister AR, Sandborn WJ. Outcome of sporadic adenomas and adenoma-like dysplasia in patients with ulcerative colitis undergoing polypectomy. Inflamm Bowel Dis 2012; 18:226-35. [PMID: 21416564 DOI: 10.1002/ibd.21687] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2011] [Accepted: 01/20/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) patients are at increased risk of colorectal dysplasia and cancer. Few studies have examined the clinical outcomes of dysplastic polyps resembling sporadic adenomas that are removed with endoscopic polypectomy. METHODS A centralized diagnostic index identified patients evaluated between 1994 and 2004 with UC and polypoid dysplasia who were followed from the time of polypectomy until the most recent colonoscopy. They were stratified into two groups by polyp occurrence, either within (adenoma-like dysplasia) or outside (sporadic adenoma) the most proximal endoscopic or histologic extent of colitis. The endpoints of interest were the development of subsequent colorectal neoplasia, flat dysplasia, or cancer. The cumulative probabilities of these endpoints were estimated using the Kaplan-Meier method, and the association with clinical factors assessed using Cox proportional hazards regression. RESULTS Ninety-five patients were found to have polypoid dysplasia; of these, 77 underwent polypectomy. The cumulative probability of subsequent colorectal neoplasia in polypectomy patients was 18% at 1 year and 69% at 5 years. After polypectomy, cumulative incidence of cancer or flat dysplasia was 2% at 1 year and 13% at 5 years. The proportional hazards models indicated that these outcomes were not significantly associated with polyp type, primary sclerosing cholangitis, family history of colorectal cancer, 5-aminosalicylate use, extent of colitis, or duration of disease. CONCLUSIONS While polypectomy may be safe for the management of adenomas occurring in most UC patients, the 5-year cumulative incidence of a combined endpoint (cancer or flat dysplasia) was 13%. Such patients should be followed closely.
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Affiliation(s)
- John B Kisiel
- Division of Gastroenterology & Hepatology, Rochester, Minnesota 55905, USA
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45
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Munding J, Ziebarth W, Pox CP, Ladigan S, Reiser M, Hüppe D, Brand L, Schmiegel W, Tannapfel A, Reinacher-Schick AC. The influence of 5-aminosalicylic acid on the progression of colorectal adenomas via the β-catenin signaling pathway. Carcinogenesis 2011; 33:637-43. [PMID: 22198215 DOI: 10.1093/carcin/bgr306] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Surveillance colonoscopy is an important strategy for prevention of colorectal cancer. 5-aminosalicylate (ASA) (mesalazine) is discussed as a chemopreventive agent as it reduces the cancer risk in ulcerative colitis patients. The current study analyses the effect of 5-ASA on Wnt/β-catenin signaling in vitro and in vivo in colon epithelial cells. The effect of 5-ASA was determined using a β-catenin/T-cell factor (TCF)-reporter assay and by western blotting in cultured colon cancer cells. Formalin fixed paraffin embedded material from 227 polyps removed from a subgroup of 56 patients, who participated in a randomized placebo-controlled 3-year prevention trial with 5-ASA was evaluated according to histomorphological characteristics and expression of β-catenin and target genes Cox2, cyclin D1 and E-cadherin as well as ornithine decarboxylase (ODC). Patients were grouped into a low-risk and a high-risk group according to the number of adenomas at initial colonoscopy. ß-catenin/TCF signaling activity was significantly reduced by 5-ASA treatment possibly through a reduction in ß-catenin levels. Moreover, 5-ASA significantly reduced ß-catenin levels and nuclear localization in patients' adenomas. In addition, 5-ASA also significantly changed expression of the downstream targets Cox2, cyclin D1 and E-cadherin, correlating with ß-catenin status. Moreover, 5-ASA significantly reduced levels of ODC in vivo. Expression of p53 was unaltered by the 5-ASA treatment. Our study shows a significant in vitro and long-term in vivo effect of 5-ASA on ß-catenin signaling as a key signaling pathway in the development of colorectal adenoma. Therefore, we suggest the use of 5-ASA as a promising drug for prevention of sporadic colorectal carcinoma.
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Affiliation(s)
- Johanna Munding
- Institute of Pathology, Ruhr-University Bochum, D-44789, Germany.
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46
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Leifeld L, Pfützer R, Morgenstern J, Gibson PR, Marakhouski Y, Greinwald R, Mueller R, Kruis W. Mesalazine granules are superior to Eudragit-L-coated mesalazine tablets for induction of remission in distal ulcerative colitis - a pooled analysis. Aliment Pharmacol Ther 2011; 34:1115-22. [PMID: 21923715 DOI: 10.1111/j.1365-2036.2011.04840.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Different oral formulations of 'mesalazine (mesalamine)' may have different efficacy in distal ulcerative colitis. AIM To evaluate the efficacy of mesalazine granules (Salofalk granules) vs. mesalazine tablets (Salofalk tablets) as induction therapy in patients with distinct extensions of ulcerative colitis. METHODS A pooled analysis of 705 patients from four prospective, randomised, double-blind phase III trials was performed. The efficacy of 8 weeks' induction with 3 g/day mesalazine granules [3 g once daily (o.d.) or 1 g three times daily (t.d.s)] vs. 3 g/day mesalazine tablets (1 g t.d.s.) was compared in terms of clinical remission (CR: CAI ≤ 4) and endoscopic remission (ER: EI ≤ 3) (both according to Rachmilewitz) in subgroups with pancolitis, left-sided colitis, or proctosigmoiditis. RESULTS Mesalazine granules were equipotent to mesalazine tablets in pancolitis regarding CR (72% vs. 71%, P = 0.909) and ER (58% vs. 49%, P = 0.338). In left-sided colitis, both mesalazine formulations were equipotent regarding CR (66% vs. 67%; P = 0.843) but mesalazine granules were superior regarding ER (56% vs. 37%; P = 0.025). In proctosigmoiditis, mesalazine granules were significantly more effective than mesalazine tablets regarding CR (78% vs. 55% P < 0.001) and ER (67% vs. 43% P < 0.001). Furthermore, o.d. application of mesalazine granules was more effective than t.d.s. dosing in left-sided colitis (CR 73% vs. 62%, P = 0.181; ER 71% vs. 48% P = 0.005) and proctosigmoiditis (CR 86% vs. 73%, P = 0.020; ER 75% vs. 61%, P = 0.021), but not in pancolitis. CONCLUSION This pooled analysis supports the hypothesis that mesalazine granules are superior to mesalazine tablets in induction of remission in distal colitis and should be taken once daily.
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Affiliation(s)
- L Leifeld
- Evangelisches Krankenhaus Kalk, Cologne, Germany.
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47
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Katsanos KH, Tatsioni A, Pedersen N, Shuhaibar M, Ramirez VH, Politi P, Rombrechts E, Pierik M, Clofent J, Beltrami M, Bodini P, Freitas J, Mouzas I, Fornaciari G, Moum B, Lakatos PL, Vermeire S, Langholz E, Odes S, Morain CO, Stockbrügger R, Munkholm P, Tsianos EV. Cancer in inflammatory bowel disease 15 years after diagnosis in a population-based European Collaborative follow-up study. J Crohns Colitis 2011; 5:430-42. [PMID: 21939917 DOI: 10.1016/j.crohns.2011.04.013] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Revised: 04/20/2011] [Accepted: 04/20/2011] [Indexed: 02/08/2023]
Abstract
AIM OF THE STUDY To determine the occurrence of intestinal and extraintestinal cancers in the 1993-2009 prospective European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort. PATIENTS-METHODS A physician per patient form was completed for 681 inflammatory bowel disease patients (445UC/236CD) from 9 centers (7 countries) derived from the original EC-IBD cohort. For the 15-year follow up period, rates of detection of intestinal and extraintestinal cancers were computed. RESULTS Patient follow-up time was fifteen years. In total 62/681 patients (9.1%) [41 with ulcerative colitis/21 with Crohn's disease, 36 males/26 females] were diagnosed with sixty-six cancers (four patients with double cancers). Colorectal cancer was diagnosed in 9/681 patients [1.3%] (1 Crohn's disease and 8 ulcerative colitis). The remaining 53 cancers were extraintestinal. There was a higher prevalence of intestinal cancer in the Northern centers compared to Southern centers [p=NS]. Southern centers had more cases of extraintestinal cancer compared to Northern centers [p=NS]. The frequency of all observed types of cancers in Northern and in Southern centers did not differ compared to the expected one in the background population. CONCLUSIONS In the fifteen-year follow up of the EC-IBD Study Group cohort the prevalence of cancer was 9.1% with most patients having a single neoplasm and an extraintestinal neoplasm. In Northern centers there were more intestinal cancers while in Southern centers there were more extraintestinal cancers compared to Northern centers. In this IBD cohort the frequency of observed cancers was not different from that expected in the background population.
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48
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Campregher C, Gasche C. Aminosalicylates. Best Pract Res Clin Gastroenterol 2011; 25:535-46. [PMID: 22122769 DOI: 10.1016/j.bpg.2011.10.013] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2011] [Revised: 08/21/2011] [Accepted: 10/27/2011] [Indexed: 02/08/2023]
Abstract
Aminosalicylates are the most common drugs for the primary treatment of inflammatory bowel disease. Various pro-drugs and formulations were developed in order to improve pharmacological profiles, optimize bioavailability and to gain highest efficacy in the treatment of ulcerative colitis (UC) and Crohn's disease. In vitro studies have greatly contributed to the understanding of the molecular actions in vivo and clinical studies have proven aminosalicylates to be effective and safe. This review summarizes the current knowledge on the molecular, pharmacological and clinical properties of aminosalicylates with respect to chemoprevention for UC-associated colorectal cancer.
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Affiliation(s)
- Christoph Campregher
- Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Division of Gastroenterology and Hepatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria
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49
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Williams C, Panaccione R, Ghosh S, Rioux K. Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease. Therap Adv Gastroenterol 2011; 4:237-48. [PMID: 21765868 PMCID: PMC3131170 DOI: 10.1177/1756283x11405250] [Citation(s) in RCA: 93] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Mesalazine [5-aminosalicylic acid (5-ASA)] has been used for over 30 years in the treatment of inflammatory bowel disease (IBD). It is a highly effective, safe, and well-tolerated drug for treatment of mild to moderate ulcerative colitis, which represents most patients with this disease. Recent studies of patient adherence to 5-ASA therapies in ulcerative colitis have highlighted the need for regimens that enable long-term compliance to significantly reduce the risk of troublesome and debilitating flares in the short term, and possibly colon cancer in the long term. Indeed, much of the recent innovation in clinical use of 5-ASA in colitis has come from studies of novel delivery mechanisms and simplified oral dosing schedules. These studies have provided much needed clarity on essential matters such as starting dose, dose escalation, and efficacy in terms of the ideal clinical endpoint - mucosal healing. Various manufacturers are re-evaluating their products to determine the safety and efficacy of such dosing regimens. Although once widely employed in the treatment of Crohn's disease (CD), the accumulated body of evidence now suggests that there is a much more limited role for 5-ASA in this particular form of inflammatory bowel disease. Recent 5-ASA randomized-controlled trials, comparative studies, and outcomes research have led to refined treatment strategies and awareness for practitioners to better inform, engage and facilitate patients in optimal use of 5-ASA in inflammatory bowel disease.
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Affiliation(s)
- Chadwick Williams
- Inflammatory Bowel Disease Research Institute, Cedars-Sinai Medical Centre, Los Angeles, CA, USA
| | - Remo Panaccione
- Inflammatory Bowel Disease Clinic, Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Subrata Ghosh
- Head of the Department of Medicine, University of Calgary, Foothills Medical Centre, Calgary, Alberta, Canada
| | - Kevin Rioux
- Division of Gastroenterology and Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, 1705 Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
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50
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5-aminosalicylate is not chemoprophylactic for colorectal cancer in IBD: a population based study. Am J Gastroenterol 2011; 106:731-6. [PMID: 21407180 DOI: 10.1038/ajg.2011.50] [Citation(s) in RCA: 87] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We aimed to determine if use of 5-aminosalicylates (5-ASA) was associated with a reduced risk of colorectal cancer (CRC) in people with inflammatory bowel disease (IBD). METHODS We used the population-based University of Manitoba IBD Epidemiology Database that tracks all health-care visits from 1984 to 2008 of all Manitobans with IBD and all prescription medication use since 1995. In 2008, there were 8,744 subjects with IBD (ulcerative colitis 4,325, Crohn's disease 4,419, females 4,851, males 3,893). In study I, we assessed the incidence of CRC among 5-ASA users (≥1 year, ≥5 years of cumulative use) compared with nonusers. In study II, we assessed a cohort of those with CRC (n=101) diagnosed in 1995-2008, matched to a control cohort by age, sex, disease duration, and disease diagnosis without CRC (n=303), and logistic analysis was undertaken. RESULTS For study I, the hazard ratio for CRC among 5-ASA users was 1.04 (95% confidence interval (CI) 0.67-1.62, P=0.87) at ≥1 year of use and 2.01 (95% CI 1.04-3.9, P=0.038) at ≥ 5 years of use with no difference when assessing by diagnosis. Males, but not females, using 5-ASA for ≥ 5 years had an increased risk of CRC. In study II, CRC cases had similar use of any 5-ASA compared with controls for ≥ 1 year of use (1.02, 95% CI 0.60-1.74) or ≥ 5 years (1.96, 95% CI 0.84-4.55), and a similar mean number of 5-ASA prescriptions at 10 vs. 11 (P=0.8) and a similar mean number of dose days at 330 vs. 410 (P=0.69). CONCLUSIONS Our results support the majority of studies to date that 5-ASA is not chemoprophylactic in IBD for CRC.
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