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Balderramo D, Quaresma AB, Olivera PA, Savio MC, Villamil MPG, Panaccione R, Ng SC, Kaplan GG, Kotze PG. Challenges in the diagnosis and treatment of inflammatory bowel disease in Latin America. Lancet Gastroenterol Hepatol 2024; 9:263-272. [PMID: 38340754 DOI: 10.1016/s2468-1253(23)00284-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/15/2023] [Accepted: 08/18/2023] [Indexed: 02/12/2024]
Abstract
The incidence and prevalence of inflammatory bowel disease (IBD), namely Crohn's disease and ulcerative colitis, have increased in Latin America over the past few decades. Although incidence is accelerating in some countries in the region, other areas in Latin America are already transitioning into the next epidemiological stage-ie, compounding prevalence-with a similar epidemiological profile to the western world. Consequently, more attention must be given to the diagnosis and management of IBD in Latin America. In this Review, we provide an overview of epidemiology, potential local environmental risk factors, challenges in the management of IBD, and limitations due to the heterogenity of health-care systems, both public and private, in Latin America. Unresolved issues in the region include inadequate access to diagnostic resources, biological therapies, tight disease monitoring (including treat to target therapy, surveillance and prevention of complications, drug monitoring), and specialised IBD surgery. Local guidelines are an important effort to overcome barriers in IBD management. Advancements in long-term health-care policies will be important to promote early diagnosis, access to new treatments, and improvements in research in Latin America. These improvements will not only affect overall health care but will also lead to optimal prioritisation of IBD-related costs and resources and enhance the quality of life of people with IBD in Latin America.
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Affiliation(s)
- Domingo Balderramo
- Gastroenterology Department, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Abel Botelho Quaresma
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná, Curitiba, Brazil; IBD Outpatient Clinic, Universidade do Oeste de Santa Catarina, Joaçaba, Brazil.
| | - Pablo A Olivera
- Inflammatory Bowel Disease Unit, Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina; Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada; Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Mariane Christina Savio
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná, Curitiba, Brazil
| | | | - Remo Panaccione
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, AB, Canada
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS institute of Health Science, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Gilaad G Kaplan
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná, Curitiba, Brazil
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Zhang L, Jin Z, Hao J. Efficacy of early biologic therapy versus late/conventional therapy in children and adolescents with Crohn's disease: A systematic review and meta-analysis. Saudi J Gastroenterol 2023; 29:259-268. [PMID: 37787346 PMCID: PMC10644997 DOI: 10.4103/sjg.sjg_190_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/17/2023] [Accepted: 08/25/2023] [Indexed: 09/19/2023] Open
Abstract
Background The objective of this study was to estimate the effectiveness of early biologics compared to conventional treatment in the management of Crohn's disease among pediatric and adolescent patients. Methods A comprehensive literature search was conducted in four electronic databases to identify relevant studies published from inception to 2023. The inclusion criteria comprised randomized controlled trials (RCTs) and cohort studies that reported on the efficacy and clinical outcomes of early biologic therapy compared to late/conventional therapy in children with Crohn's disease. The quality of the studies was assessed using the Cochrane Risk of Bias tool and the Newcastle Ottawa scale. Results A total of 13 studies (2 RCTs and 11 cohort studies), involving 861 patients, were included in the meta-analysis. The results demonstrated that early biologic therapy was associated with a significantly higher rate of clinical remission (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.10-1.54), lower relapse rates (RR 0.33, 95% CI 0.21-0.53), and improved mucosal healing (RR 1.47, 95% CI 1.10-1.97) compared to late/conventional therapy. However, it should be noted that there was evidence of publication bias among studies reporting clinical remission. Conclusion In conclusion, early biologic therapy is significantly more effective in achieving clinical remission (within two years of diagnosis), promoting mucosal healing, and reducing relapse rates in pediatric and adolescent patients with Crohn's disease, compared to late/conventional therapy. These findings emphasize the importance of initiating biological therapy early in the treatment of Crohn's disease in this patient population.
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Affiliation(s)
- Lei Zhang
- Department of Pediatric Digestive, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhixiao Jin
- Department of Pediatric Digestive, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia Hao
- Department of Pediatric Digestive, Shengjing Hospital of China Medical University, Shenyang, China
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Durak MB, Simsek C, İnan B, Yuksel I. Ileocecal valve that cannot be intubated in Crohn's disease: is this a sign of poor prognosis? Int J Colorectal Dis 2023; 38:103. [PMID: 37072530 DOI: 10.1007/s00384-023-04401-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/06/2023] [Indexed: 04/20/2023]
Abstract
BACKGROUND In Crohn's disease (CD), the inability to intubate the ileocecal valve during colonoscopy may be associated with a poor disease prognosis. In this study, we aimed to compare the long-term outcomes of CD patients with and without ileocecal valve intubation during colonoscopy to assess its value as a prognostic parameter. METHODS This retrospective study involved CD patients with isolated ileal involvement who underwent colonoscopy between 1993 and 2022. We compared the basic characteristics and long-term clinical outcomes of two groups of patients: those with intubated and non-intubated ileocecal valves during colonoscopy. RESULTS Of the 155 participants, 97 (62.5%) patients' ileum could be intubated and 58 (37.5%) could not be intubated. The non-intubated group was younger at diagnosis (39 years versus 30.5 years, p = 0.002), but other baseline characteristics such as sex, smoking status, disease duration, perianal disease, and upper gastrointestinal involvements were similar. The non-intubated group had higher rates of steroid dependence (67.2% versus 46.4%; p = 0.012), biologic treatment (89.7% versus 58.8%; p < 0.001), CD-related hospitalization (81% versus 24.7%; p < 0.001), and major abdominal surgery (58.6% versus 15.5%; p < 0.001). In the logistic regression analysis, the positive predictors of successful ileum intubation were inflammatory type CD (OR: 14.821), high serum albumin level (OR: 5.919), and older age (OR: 1.069), while the negative predictors were stenosing (OR: 0.262) and penetrating (OR: 0.247) CD behavior. CONCLUSIONS In Crohn's disease patients with isolated ileal involvement, ileocecal valve cannot be intubated during colonoscopy may indicate the severity of the disease.
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Affiliation(s)
- Muhammed Bahaddin Durak
- Department of Gastroenterology, Ankara City Hospital, Bilkent Avenue, 06800, Cankaya, Ankara, Turkey.
| | - Cem Simsek
- Department of Gastroenterology, Health Sciences University, Mehmet, Akif Inan Training and Research Hospital, Sanliurfa, Turkey
- Graduate School of Health Sciences, Hacettepe University, Ankara, Turkey
| | - Bayram İnan
- Department of Gastroenterology, Ankara City Hospital, Bilkent Avenue, 06800, Cankaya, Ankara, Turkey
| | - Ilhami Yuksel
- Department of Gastroenterology, Ankara City Hospital, Bilkent Avenue, 06800, Cankaya, Ankara, Turkey
- Department of Gastroenterology, Ankara Yildirim Beyazit University School of Medicine, Ankara, Turkey
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Mosli MH, Almudaiheem HY, AlAmeel T, Bakkari SA, Alharbi OR, Alenzi KA, Khardaly AM, AlMolaiki MA, Al-Omari BA, Albarakati RG, Al-Jedai AH, Saadah OI, Almadi MA, Al-Bawardy B. Saudi Arabia consensus guidance for the diagnosis and management of adults with inflammatory bowel disease. Saudi J Gastroenterol 2022; 29:361671. [PMID: 36412460 PMCID: PMC10540981 DOI: 10.4103/sjg.sjg_277_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/23/2022] [Accepted: 09/05/2022] [Indexed: 02/10/2023] Open
Abstract
Optimal management of inflammatory bowel disease (IBD) relies on a clear understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This article provides concise guidelines for the management of IBD in adults, based on the most up-to-date information at the time of writing and will be regularly updated. These guidelines were developed by the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacy. After an extensive literature review, 78 evidence-and expert opinion-based recommendations for diagnosing and treating ulcerative colitis and Crohn's disease in adults were proposed and further refined by a voting process. The consensus guidelines include the finally agreed on statements with their level of evidence covering different aspects of IBD diagnosis and treatment.
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Affiliation(s)
- Mahmoud H. Mosli
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | | | - Turki AlAmeel
- Department of Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Shakir A. Bakkari
- Division of Gastroenterology, King Saud Medical City, Riyadh, Saudi Arabia
| | - Othman R. Alharbi
- Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Khalidah A. Alenzi
- Regional Drug Information and Pharmacovigilance Center, Ministry of Health, Tabuk, Saudi Arabia
| | | | - Maha A. AlMolaiki
- Department of Pharmaceutical Care, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Bedor A. Al-Omari
- Pharmaceutical Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Rayan G. Albarakati
- Department of Obstetrics and Gynecology, Majmaah University, Riyadh, Saudi Arabia
| | - Ahmed H. Al-Jedai
- Deputyship of Therapeutic Affairs, Ministry of Health, Riyadh, Saudi Arabia
| | - Omar I. Saadah
- Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Majid A. Almadi
- Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Badr Al-Bawardy
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
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Banerjee R, Ali RAR, Wei SC, Adsul S. Biologics for the Management of Inflammatory Bowel Disease: A Review in Tuberculosis-Endemic Countries. Gut Liver 2021; 14:685-698. [PMID: 33191310 PMCID: PMC7667923 DOI: 10.5009/gnl19209] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 11/01/2019] [Accepted: 11/25/2019] [Indexed: 12/17/2022] Open
Abstract
The advent of biologics and biologic therapy has transformed the management of inflammatory bowel disease (IBD) with enhanced early and adequate responses to treatment, fewer hospitalizations, a reduced need for surgery, and unprecedented outcomes including complete mucosal and histologic healing. However, an important issue with the use of anti-tumor necrosis factor (anti-TNF) agents in IBD is the increased risk of tuberculosis (TB). This is compounded by the diagnostic dilemma when differentiating between Crohn’s disease and gastrointestinal TB, and the potentially serious consequences of initiating an incorrect treatment in the case of misdiagnosis. The interplay between IBD and TB is most relevant in Asia, where more than 60% of the 10.4 million new TB cases in 2016 were reported. A number of studies have reported an increased risk of TB with anti-TNF agents, including in patients who had tested negative for TB prior to treatment initiation. The limited evidence currently available regarding adhesion molecule antagonists such as vedolizumab suggests a comparatively lower risk of TB, thus making them a promising option for IBD management in TB-endemic regions. This comprehensive review examines the available literature on the risk of TB with the use of biologics in the TB-endemic regions of Asia, focusing on the diagnostic dilemma, the risk of reactivation, and the optimized management algorithms for latent and active disease.
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Affiliation(s)
- Rupa Banerjee
- IBD Center, Asian Institute of Gastroenterology, Hyderabad, India
| | - Raja Affendi Raja Ali
- Gastroenterology Unit, Department of Medicine, Faculty of Medicine, The National University of Malaysia, Kuala Lumpur, Malaysia
| | - Shu Chen Wei
- Department of Internal Medicine, IBD Clinical and Basic Research Integrated Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shashi Adsul
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
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Yang QY, Ma LL, Zhang C, Lin JZ, Han L, He YN, Xie CG. Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF-κB Signaling Pathway and Gut Microbiota. Front Pharmacol 2021; 12:674416. [PMID: 34366843 PMCID: PMC8339204 DOI: 10.3389/fphar.2021.674416] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/18/2021] [Indexed: 12/14/2022] Open
Abstract
Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear. Purpose: This study aimed to evaluate the protective effect and mechanism of indigo naturalis to treat mice with dextran sulfate sodium (DSS)-induced UC. Methods: DSS-induced UC mice were treated with indigo naturalis (200 mg/kg), indigo (4.76 mg/kg), and indirubin (0.78 mg/kg) for 1 week. The anti-UC mechanism of indigo naturalis was studied by pathological section, inflammatory factor, western blot, and 16S rRNA sequencing. Results: According to body weight change, disease activity index, and colon length, indigo naturalis had the strongest anti DSS-induced UC effect, followed by indirubin and indigo. Pathological section showed that indigo naturalis, indigo, and indirubin could reduce the infiltration of inflammatory cells, increase the secretion of intestinal mucus, and repair the intestinal mucosa. Indigo naturalis, indigo, and indirubin could reduce IL-1β,IL-6, and TNF-α by inhibiting TLR4/MyD88/NF-κB signal transduction. Indigo naturalis and indigo could also reduce IgA and IgG both in serum and colon tissue. In addition, indigo naturalis, indigo, and indirubin could adjust the gut microbiota structure of DSS-induced UC mice, reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of probiotics. Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction.
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Affiliation(s)
- Qi-Yue Yang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Le-le Ma
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chen Zhang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jun-Zhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Li Han
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ya-Nan He
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chun-Guang Xie
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Shi L, Lu BL, Qiu Y, Huang L, Huang SY, Mao R, Lin JJ, Du JF, Feng ST, Li ZP, Sun CH, Li XH. Hepatic mosaic enhancement pattern correlates with increased inflammatory activity and adverse therapeutic outcomes in patients with Crohn's disease. Abdom Radiol (NY) 2021; 46:3149-3158. [PMID: 33646351 DOI: 10.1007/s00261-021-02979-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 01/25/2021] [Accepted: 02/09/2021] [Indexed: 11/24/2022]
Abstract
PURPOSE This study aimed to evaluate the role of hepatic mosaic enhancement pattern (HMEP) on computed tomography images in the disease activity and therapeutic outcome of Crohn's Disease (CD). METHODS Twenty-five CD patients with HMEP comprised the HMEP group, and 25 CD patients without HMEP, who had a similar onset age, sex, and disease course with those in the HMEP group, comprised the non-HMEP group. No underlying liver/biliary disease was observed in any of the patients. Clinical characteristics, laboratory test results, Lémann index, and CD endoscopic index of severity (CDEIS) were compared between the groups using the Student t-, Mann-Whitney U, Chi square, or Fisher's exact tests. Patients received top-down, step-up, or traditional treatment during the follow-up period. After the 1-year follow-up, therapeutic outcomes (active inflammation [CDEIS > 3.5 if the endoscopic data were available, or C-reactive protein level > 5 mg/L if the endoscopic data were unavailable] or remission) were evaluated. RESULTS The occurrence rate of fistulas/abscesses was higher in the HMEP group (84%, 21/25) than in the non-HMEP group (48%, 12/25) with no statistical significance (P = 0.056). The HMEP group showed a higher C-reactive protein level (P = 0.001), erythrocyte sedimentation rate (P = 0.013), and blood platelet count (P = 0.005). There was no significant difference in therapeutic strategies between the groups (P = 0.509). The HMEP group showed a significantly lower remission ratio after anti-inflammatory treatment than the non-HMEP group (P = 0.045). CONCLUSIONS HMEP was correlated with increased inflammatory activity and adverse therapeutic outcomes in CD. This finding provided insights regarding novel markers of CD diagnosis and treatment.
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Affiliation(s)
- Li Shi
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
- Department of Radiology, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Guangzhou, 510150, People's Republic of China
| | - Bao-Lan Lu
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Li Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Si-Yun Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Jin-Jiang Lin
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Jin-Fang Du
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China
| | - Can-Hui Sun
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
| | - Xue-Hua Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
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Cao WT, Huang R, Jiang KF, Qiao XH, Wang JJ, Fan YH, Xu Y. Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review. World J Gastroenterol 2021; 27:886-907. [PMID: 33727776 PMCID: PMC7941861 DOI: 10.3748/wjg.v27.i9.886] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 12/25/2020] [Accepted: 01/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.
AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.
METHODS We searched PubMed/MEDLINE, Embase, and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.
RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6 μg/mL in IBD. Blood concentration of infliximab reaching 5.0-12.7 μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease. Blood concentration of adalimumab reaching 7.2-16.2 μg/mL or more could predict mucosal healing in IBD. The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8 μg/mL in perianal fistulizing Crohn's disease. Blood concentration of vedolizumab surpassing 25.0 μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 μg/mL.
CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies, whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.
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Affiliation(s)
- Wan-Ting Cao
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Rong Huang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Ke-Fang Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Xue-Hui Qiao
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Jing-Jing Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Yi-Hong Fan
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Yi Xu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
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Edwards SJ, Barton S, Bacelar M, Karner C, Cain P, Wakefield V, Marceniuk G. Prognostic tools for identification of high risk in people with Crohn's disease: systematic review and cost-effectiveness study. Health Technol Assess 2021; 25:1-138. [PMID: 33783345 PMCID: PMC8040347 DOI: 10.3310/hta25230] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Crohn's disease is a lifelong condition that can affect any segment of the gastrointestinal tract. Some people with Crohn's disease may be at higher risk of following a severe course of disease than others and being able to identify the level of risk a patient has could lead to personalised management. OBJECTIVE To assess the prognostic test accuracy, clinical impact and cost-effectiveness of two tools for the stratification of people with a diagnosis of Crohn's disease by risk of following a severe course of disease. DATA SOURCES The data sources MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were searched to inform the systematic reviews on prognostic accuracy, clinical impact of the prognostic tools, and economic evaluations. Additional data sources to inform the review of economic evaluations were NHS Economic Evaluation Database, Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database. REVIEW METHODS Systematic reviews of electronic databases were carried out from inception to June 2019 for studies assessing the prognostic accuracy and clinical impact of the IBDX® (Crohn's disease Prognosis Test; Glycominds Ltd, Lod, Israel) biomarker stratification tool and the PredictSURE-IBD™ (PredictImmune Ltd, Cambridge, UK) tool. Systematic reviews of studies reporting on the cost-effectiveness of treatments for Crohn's disease were run from inception to July 2019. Two reviewers independently agreed on studies for inclusion, assessed the quality of included studies and validated the data extracted from studies. Clinical and methodological heterogeneity across studies precluded the synthesis of data for prognostic accuracy. A de novo economic model was developed to compare the costs and consequences of two treatment approaches - the 'top-down' and 'step-up' strategies, with step-up considered standard care - in people at high risk of following a severe course of Crohn's disease. The model comprised a decision tree and a Markov cohort model. RESULTS Sixteen publications, including eight original studies (n = 1478), were deemed relevant to the review of prognostic accuracy. Documents supplied by the companies marketing the prognostic tools were also reviewed. No study meeting the eligibility criteria reported on the sensitivity or specificity of the IBDX biomarker stratification tool, whereas one study provided estimates of sensitivity, specificity and negative predictive value for the PredictSURE-IBD tool. All identified studies were observational and were considered to provide weak evidence on the effectiveness of the tools. Owing to the paucity of data on the two tools, in the base-case analysis the accuracy of PredictSURE-IBD was assumed to be 100%. Accuracy of IBDX was assumed to be 100% in a scenario analysis, with the cost of the tests being the only difference between the analyses. The incremental analysis of cost-effectiveness demonstrated that top-down (via the use of PredictSURE-IBD in the model) is more expensive and generates fewer quality-adjusted life-years than step-up (via the standard care arm of the model). LIMITATIONS Despite extensive systematic searches of the literature, no robust evidence was identified of the prognostic accuracy of the biomarker stratification tools IBDX and PredictSURE-IBD. CONCLUSIONS Although the model indicates that standard care dominates the tests, the lack of evidence of prognostic accuracy of the two tests and the uncertainty around the benefits of the top-down and step-up treatment approaches mean that the results should be interpreted as indicative rather than definitive. STUDY REGISTRATION This study is registered as PROSPERO CRD42019138737. FUNDING This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 23. See the NIHR Journals Library website for further project information.
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10
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Differences in inflammatory bowel diseases between East and West: a Chinese perspective. J Public Health (Oxf) 2021. [DOI: 10.1007/s10389-019-01102-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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11
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Fecal calprotectin: current and future perspectives for inflammatory bowel disease treatment. Eur J Gastroenterol Hepatol 2020; 32:1091-1098. [PMID: 32282400 DOI: 10.1097/meg.0000000000001731] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Fecal calprotectin has been widely studied in inflammatory bowel disease (IBD) under clinical and therapeutic settings. It showed a good correlation with clinical, endoscopic, and histologic findings. For these reasons, fecal calprotectin is currently one of the most useful tools in IBD care, both in diagnosis and in clinical management. The development of biologic drugs allowed a deeper control of disease, which sometimes reaches histological healing; this is associated with a reduced risk of relapses and complications. The management of IBD treatment is currently carried out with a treat-to-target approach, and mucosal healing is considered at present to be the optimal therapeutic target, but the future is going through histologic remission. Fecal calprotectin is probably the best marker of mucosal healing, but it is correlated also with histologic remission: moreover, it has been recently studied as a possible therapeutic target in the CALM study. We carried out a comprehensive literature review in order to evaluate the role of fecal calprotectin at present and in the future in the management of IBD therapies.
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12
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Park J, Yoon H, Shin CM, Park YS, Kim N, Lee DH. Higher levels of disease-related knowledge reduce medical acceleration in patients with inflammatory bowel disease. PLoS One 2020; 15:e0233654. [PMID: 32502199 PMCID: PMC7274391 DOI: 10.1371/journal.pone.0233654] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 05/09/2020] [Indexed: 02/06/2023] Open
Abstract
Background and aims The disease-related knowledge levels in patients with inflammatory bowel disease (IBD) are important because it could affect the self-management ability and adaptive coping strategies. We set out to determine whether higher levels of disease-related knowledge reduce medical acceleration. Methods We evaluated the levels of disease-related knowledge in all patients at the time of enrollment for SNUBH IBD cohort using the validated IBD-KNOW questionnaire. Clinical data were prospectively collected and the factors related to step-up therapy were analyzed. Step-up therapy was defined as the new use of corticosteroids, immunomodulators, or biologics after the enrollment. Results Between April 2017 and January 2019, 298 patients were enrolled (mean age, 39.8 years; males, 69.5%); 193 patients (64.8%) had ulcerative colitis and 105 (35.2%) had Crohn’s disease. The mean disease duration was 35.8 months. During the mean follow-up of 14.7 months, 90 patients (30.2%) underwent step-up therapy and 208 (69.8%) underwent continuous therapy. The prevalence of continuous therapy increased with increasing IBD-KNOW scores (p for trend = 0.019). Cox proportional hazards analysis revealed that high IBD-KNOW scores (≥ 16) (hazards ratio [HR]: 0.498, 95% confidence interval [CI]: 0.276–0.897, p = 0.020) was negatively associated with the step-up therapy. Conclusions Higher disease-related knowledge could reduce the requirement of step-up therapy in IBD. The IBD-KNOW score was independently predictive of step-up therapy.
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Affiliation(s)
- Jihye Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- * E-mail:
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Ramos López L, Hernández Camba A, Rodríguez-Lago I, Carrillo Palau M, Cejas Dorta L, Elorza A, Alonso Abreu I, Vela M, Hidalgo A, Hernández Álvarez-Builla N, Rodríguez GE, Rodríguez Y, Tardillo C, Díaz-Flórez L, Eiroa D, Aduna M, Garrido MS, Larena JA, Cabriada JL, Quintero Carrion E. Usefulness of magnetic resonance enterography in the clinical decision-making process for patients with inflammatory bowel disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:439-445. [PMID: 32349904 DOI: 10.1016/j.gastrohep.2020.03.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/04/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the impact of magnetic resonance enterography (MRE) diagnosis on clinical decision-making regarding treatment choice and maintenance of treatment over time in patients with inflammatory bowel disease (IBD). METHODS A cohort of patients who underwent MRE for IBD assessment between 2011 and 2014 was analyzed. From clinical records, we retrospectively retrieved their demographic data and clinical data on their IBD at the time of MRE, the results of MRE and the patient's clinical course. Medical management decisions made during the three months following MRE and at the 15-month follow-up were assessed. RESULTS In total, 474 MREs were reviewed. In the first three-month period, MRE results led to changes in the medical management of 266 patients (56.1%). Of those, maintenance therapy was altered in 140 patients (68.3%) (90.7% step-up and 9.3% top-down strategy), 65 (24.4%) were prescribed a course of steroids and 61 (22.9%) underwent surgery. MRE confirmed a CD diagnosis in 14/41 patients (34.1%) previously diagnosed with indeterminate colitis or ulcerative colitis and in 4/18 patients (22.2%) with suspected IBD. At the 15-month follow-up, treatment remained unchanged in 289 patients (65.8%). CONCLUSIONS These results suggest that MRE is a diagnostic tool that provides valid information for the clinical-decision making process for patients with CD.
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Affiliation(s)
- Laura Ramos López
- Servicio de Aparato Digestivo, Hospital Universitario de Canarias, Tenerife, Spain
| | - Alejandro Hernández Camba
- Servicio de Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain.
| | | | - Marta Carrillo Palau
- Servicio de Aparato Digestivo, Hospital Universitario de Canarias, Tenerife, Spain
| | - Luis Cejas Dorta
- Servicio de Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain
| | - Ainara Elorza
- Servicio de Aparato Digestivo, Hospital de Galdakao, Galdakao, Spain
| | | | - Milagros Vela
- Servicio de Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain
| | - Alba Hidalgo
- Servicio de Aparato Digestivo, Hospital de Galdakao, Galdakao, Spain
| | | | - G Esther Rodríguez
- Servicio de Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain
| | - Yolanda Rodríguez
- Servicio de Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain
| | - Carlos Tardillo
- Servicio de Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain
| | - Lucio Díaz-Flórez
- Servicio de Radiología, Hospital Universitario de Canarias, Tenerife, Spain
| | - Daniel Eiroa
- Servicio de Radiología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain
| | - Marta Aduna
- Osatek, Hospital de Galdakao, Galdakao, Spain
| | - María S Garrido
- Servicio de Radiología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain
| | | | - José L Cabriada
- Servicio de Aparato Digestivo, Hospital de Galdakao, Galdakao, Spain
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Berends SE, Strik AS, Löwenberg M, D'Haens GR, Mathôt RAA. Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Ulcerative Colitis. Clin Pharmacokinet 2020; 58:15-37. [PMID: 29752633 PMCID: PMC6326086 DOI: 10.1007/s40262-018-0676-z] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology, probably caused by a combination of genetic and environmental factors. The treatment of patients with active UC depends on the severity, localization and history of IBD medication. According to the classic step-up approach, treatment with 5-aminosalicylic acid compounds is the first step in the treatment of mild to moderately active UC. Corticosteroids, such as prednisolone are used in UC patients with moderate to severe disease activity, but only for remission induction therapy because of side effects associated with long-term use. Thiopurines are the next step in the treatment of active UC but monotherapy during induction therapy in UC patients is not preferred because of their slow onset. Therapeutic drug monitoring (TDM) of the pharmacologically active metabolites of thiopurines, 6-thioguanine nucleotide (6-TGN), has proven to be beneficial. Thiopurine S-methyltransferase (TMPT) plays a role in the metabolic conversion pathway of thiopurines and exhibits genetic polymorphism; however, the clinical benefit and relevance of TPMT genotyping is not well established. In patients with severely active UC refractory to corticosteroids, calcineurin inhibitors such as ciclosporin A (CsA) and tacrolimus are potential therapeutic options. These agents usually have a rather rapid onset of action. Monoclonal antibodies (anti-tumor necrosis factor [TNF] agents, vedolizumab) are the last pharmacotherapeutic option for UC patients before surgery becomes inevitable. Body weight, albumin status and antidrug antibodies contribute to the variability in the pharmacokinetics of anti-TNF agents. Additionally, the use of concomitant immunomodulators (thiopurines/methotrexate) lowers the rate of immunogenicity, and therefore the concomitant use of anti-TNF therapy with an immunomodulator may confer some advantage compared with monotherapy in certain patients. TDM of anti-TNF agents could be beneficial in patients with primary nonresponse and secondary loss of response. The potential benefit of applying TDM during vedolizumab treatment has yet to be determined.
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Affiliation(s)
- Sophie E Berends
- Department Hospital Pharmacy, Academic Medical Center, Amsterdam, The Netherlands.
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
| | - Anne S Strik
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Mark Löwenberg
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Geert R D'Haens
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Ron A A Mathôt
- Department Hospital Pharmacy, Academic Medical Center, Amsterdam, The Netherlands
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Lindholm CR, Siegel CA. Are We Ready to Include Prognostic Factors in Inflammatory Bowel Disease Trials? Curr Pharm Des 2020; 25:64-68. [PMID: 30864506 DOI: 10.2174/1381612825666190312113935] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 03/06/2019] [Indexed: 12/24/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by periodic episodes of flares and remission. Treatment is aimed at healing the bowel, to ultimately decrease hospitalization rates, need for surgeries and overall disability. In more recent years, treatment has transitioned from a reactive approach to a more proactive approach focusing on treating disease earlier and preventing complications. The challenge lies in identifying patients who need more intensive treatment early and trying to determine who will respond to which medications. Biomarkers and clinical activity scoring systems can be used to help guide treatment decisions. However, IBDs are very heterogeneous and the significance of these biomarkers can be difficult to discern on an individual basis. Recently, prognostic tools have been developed to aid in determining a patient's prognosis as well as their likelihood to respond to different therapies. Despite this progress, clinical trials have not routinely adopted this approach in their study design. Tools for stratification of disease severity and to personalize treatment choices have the potential to improve our studies both by enriching the patient population and further guiding clinical decision making in practice. This review aims to discuss biomarkers, current prognosticating tools, tools that determine response to therapy and how incorporating these into clinical trials will be beneficial.
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Affiliation(s)
- Christopher R Lindholm
- Dartmouth Hitchcock Medical Center, Department of Medicine, Lebanon, NH 03766, United States
| | - Corey A Siegel
- Dartmouth Hitchcock Medical Center, Section of Gastroenterology and Hepatology, Lebanon, NH 03756, United States
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Selinger C, Carbonell J, Kane J, Omer M, Ford AC. Acceptability of a 'treat to target' approach in inflammatory bowel disease to patients in clinical remission. Frontline Gastroenterol 2020; 12:30-38. [PMID: 33493249 PMCID: PMC7802490 DOI: 10.1136/flgastro-2019-101366] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 01/08/2020] [Accepted: 01/11/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND A 'treat to target' approach aiming for remission of clinical symptoms and absence of mucosal inflammation has been proposed in inflammatory bowel disease (IBD). We aimed to establish whether patients with IBD in clinical remission find this approach acceptable. METHODS Patients in glucocorticosteroid-free clinical remission underwent a face-to-face structured, quantitative interview and rated the acceptability of treat to target on a 10-point Likert scale. We analysed factors associated with agreement to treat to target. RESULTS The cohort comprised 298 patients (144 Crohn's disease, 136 ulcerative colitis, 18 IBD-unclassified). Elevated C-reactive protein was found in 24.4% and elevated faecal calprotectin in 17.7%. Overall, 66.2% of patients rated a treat to target approach as acceptable (Likert scale ≥8). Acceptable treatment aims for patients were avoidance of flare, hospitalisation, surgery and colorectal cancer. Using binary logistic regression analysis the following were not predictive of accepting a treat to target approach: age, diagnosis, disease phenotype, surgical history, disease duration, patient knowledge, adherence, anxiety, depression and patient-reported control of disease. Better adherence to current therapy was associated with accepting a treat to target approach (B=0.16, p=0.039). CONCLUSION In a cohort of patients in clinical remission, where this strategy is most relevant, two-thirds of patients agreed with treat to target. Patients with better current adherence were more likely to accept treat to target. Patient education and counselling materials will need to be developed to convince a substantial minority of patients of the importance of treat to target.
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Affiliation(s)
- Christian Selinger
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute of Medical Research at St James's Hopsital, University of Leeds, Leeds, UK
| | - Jenelyn Carbonell
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - John Kane
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Mandour Omer
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Alexander Charles Ford
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute of Medical Research at St James's Hopsital, University of Leeds, Leeds, UK
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Burr NE, Lord R, Hull MA, Subramanian V. Decreasing Risk of First and Subsequent Surgeries in Patients With Crohn's Disease in England From 1994 through 2013. Clin Gastroenterol Hepatol 2019; 17:2042-2049.e4. [PMID: 30583051 DOI: 10.1016/j.cgh.2018.12.022] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 10/31/2018] [Accepted: 12/07/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Gastrointestinal (GI) surgery is an important part of the treatment algorithm for patients with Crohn's disease (CD) that is complicated or does not respond to medical therapy. Cohort studies from Denmark and Canada have shown that the risk of primary surgery is decreasing but there is a lack of contemporary data on subsequent resections. We examined trends in first and second GI resections in patients with CD. METHODS We performed a retrospective cohort study using the United Kingdom primary care database ResearchOne, collecting data from patients with Crohn's disease from 1994 through 2013. We compared rates of first and second GI resections with etiological factors. RESULTS Among 3059 incident cases of CD, 13%, 21%, and 26% of the patients underwent surgical resections after 1, 5, and 10 years, respectively. Of patients with an initial resection, 20% required an additional operation when followed for 10 years after the initial resection. We found a significant reduction in first surgery, from 44% to 21% after 10 years of disease, from 1994 to 2003 (χ2 for trend, P < .05). There was a significant reduction in second resections, in a 10-year follow-up period, from 40% in 1994 to 17% in 2003 (χ2 for trend, P < .05). Duration of disease, younger age at diagnosis, smoking, and immunomodulator use were positively associated with first surgeries. Duration of disease was significantly associated with the risk of undergoing a second resection. CONCLUSION In a retrospective analysis of a United Kingdom primary care database, we observed a significant reduction in first and subsequent GI surgeries among patients with CD over the past 20 years in England.
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Affiliation(s)
- Nicholas E Burr
- Leeds Institute of Biomedical & Clinical Sciences, University of Leeds, Leeds, United Kingdom; Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Richard Lord
- Leeds Institute of Biomedical & Clinical Sciences, University of Leeds, Leeds, United Kingdom; Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Mark A Hull
- Leeds Institute of Biomedical & Clinical Sciences, University of Leeds, Leeds, United Kingdom; Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Venkataraman Subramanian
- Leeds Institute of Biomedical & Clinical Sciences, University of Leeds, Leeds, United Kingdom; Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
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Peyrin-Biroulet L, Danese S, Cummings F, Atreya R, Greveson K, Pieper B, Kang T. Anti-TNF biosimilars in Crohn's Disease: a patient-centric interdisciplinary approach. Expert Rev Gastroenterol Hepatol 2019; 13:731-738. [PMID: 31322440 DOI: 10.1080/17474124.2019.1645595] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Introduction: The purpose of this review is to highlight the role of biosimilars in early treatment in IBD and introduce ways to facilitate a patient-centric switching process through multidisciplinary approach. Areas covered: We summarize existing scientific literature related to the role of biosimilars in inflammatory bowel disease in terms of early treatment and cost-saving and implementing switching process. Expert opinion: Use of anti-TNF biosimilars in patients has the potential for large drug-acquisition cost-saving, which can be reinvested into early treatment. Managed switched programs for adalimumab can add further benefits in the future.
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Affiliation(s)
- Laurent Peyrin-Biroulet
- a Department of gastroenterology, Nancy University Hospital, Lorraine University , Nancy , France
| | - Silvio Danese
- b IBD center department of gastroenterology and Humanitas University, Humanitas Research Hospital , Milan , Italy
| | - Fraser Cummings
- c IBD Center and Department of Biomedical Sciences, University Hospital Southampton , Southampton , UK
| | - Raja Atreya
- d Medical Department 1, University of Erlangen-Nürnberg , Erlangen , Germany
| | - Kay Greveson
- e Center for Gastroenterology, Royal Free Hospital , London , UK
| | - Burkhard Pieper
- f Scientific Affairs Biosimilars, Biogen International GmbH , Baar , Switzerland
| | - Taegyun Kang
- g Medical Affairs, Samsung Bioepis Co., Ltd , Incheon , Republic of Korea
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Schwartzberg DM, Brandstetter S, Grucela AL. Crohn's Disease of the Esophagus, Duodenum, and Stomach. Clin Colon Rectal Surg 2019; 32:231-242. [PMID: 31275069 PMCID: PMC6606321 DOI: 10.1055/s-0039-1683850] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Upper gastrointestinal Crohn's is an under-reported, under-recognized phenotype of Crohn's disease. Routine screening in the pediatric population has shown a higher prevalence compared with adults; however, most adult patients remain asymptomatic with respect to upper gastrointestinal Crohn's disease. For the patients who are symptomatic, medical treatment is the first line of management, except for cases of obstruction, perforation, or bleeding. Though most patients respond to medical therapy, mainly steroids, with the addition of immunomodulators and more recently biologics agents, surgical intervention is usually required only for obstructing gastroduodenal disease secondary to strictures. Strictureplasty and bypass are safe operations with comparable morbidity, although bypass has higher rates of dumping syndrome and marginal ulceration in the long term. Rare cases of gastroduodenal fistulous disease from active distal disease may involve the stomach or duodenum, and esophageal Crohn's disease can fistulize to surrounding structures in the mediastinum which may require the highly morbid esophagectomy.
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Affiliation(s)
- David M. Schwartzberg
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Stephen Brandstetter
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Alexis L. Grucela
- Division of Colon and Rectal Surgery, New York University Langone Medical Center, New York, New York
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Song JH, Hong SN, Lee JE, Kim K, Kim TJ, Kim ER, Chang DK, Kim YH. C-Reactive protein reduction rate following initiation of anti-tumor necrosis factor α induction therapy predicts secondary loss of response in patients with Crohn's disease. Scand J Gastroenterol 2019; 54:876-885. [PMID: 31303093 DOI: 10.1080/00365521.2019.1638962] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background/aim: The objective of this study is to identify clinical predictors of primary non-response (PNR) and secondary loss of response (LOR), in Crohn's disease (CD) patients treated with anti-tumor necrosis factor α (anti-TNF) agents. Methods: This retrospective, longitudinal, and observational cohort study included 283 patients with CD who received anti-TNF treatments from November 2006 to July 2017 at Samsung Medical Center, Seoul, Korea. Results: A total of 212 patients with CD were eligible and based on clinical responses, divided into three groups: PNR, LOR, and responder groups. PNR occurred in 13 patients (6.1%). C-Reactive protein (CRP) level at initiation of anti-TNF (baseline CRP) was a possible predictor of PNR compared to the non-PNR group (baseline CRP >1 mg/dl, OR = 4.34, 95% CI = 1.06-17.83, p = .042). During maintenance therapy, incidence of LOR was 12.2% at 1-year, 23.6% at 2-years, 36.3% at 3-years, and 52.1% at 5-years. Combining baseline CRP level and CRP reduction rate [(CRP at 12-14 weeks-baseline CRP)/baseline CRP] was a possible predictor of 1-year LOR compared to the responder group (baseline CRP >1 mg/dl and CRP reduction rate > -70%, OR = 18.86, 95% CI = 3.40-104.55, p = .001). In the Cox hazard proportional model, a combination of baseline CRP level and CRP reduction rate was possible predictors of long-term LOR during maintenance therapy (baseline CRP >1 mg/dl and CRP reduction rate > -70%, HR = 5.84, 95% CI = 2.75-12.41, p < .001). Conclusions: Baseline CRP level and CRP reduction rate might be clinical predictors for PNR or LOR to anti-TNF in patients with CD, and could guide proper therapeutic interventions in patients with CD.
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Affiliation(s)
- Joo Hye Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea
| | - Jung Eun Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea
| | - Kyunga Kim
- Research Institute for Future Medicine, Samsung Medical Center, Biostatistics and Clinical Epidemiology Center , Seoul , Korea
| | - Tae Jun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea
| | - Eun Ran Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea
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Mohan LJ, Daly JS, Ryan BM, Ramtoola Z. The future of nanomedicine in optimising the treatment of inflammatory bowel disease. Scand J Gastroenterol 2019; 54:18-26. [PMID: 30678499 DOI: 10.1080/00365521.2018.1563805] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
There have been major advancements in the treatment of inflammatory bowel disease (IBD) over the past three decades. However despite significant progress, the best available treatments continue to demonstrate variable efficacy in patients and are associated with adverse effects. Therefore there remains an unmet clinical need for ongoing therapeutic advances for IBD. In recent years nanomedicines have emerged as promising diagnostic and therapeutic tools. Nanoparticles in particular show promise to facilitate targeted oral drug delivery in IBD. Here we discuss the pitfalls of current therapies and explore the potential for nanoparticles to improve the treatment of IBD. This review examines the range of conventional and novel therapies which have benefited from nanoparticle-mediated delivery and highlights the proven therapeutic efficacy of this approach in preclinical models. These strategies under development represent a novel and innovative treatment for IBD.
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Affiliation(s)
- Lauren J Mohan
- a Division of Biology, Department of Anatomy , Royal College of Surgeons in Ireland , Dublin , Ireland.,b School of Pharmacy, Royal College of Surgeons in Ireland , Dublin , Ireland
| | - Jacqueline S Daly
- a Division of Biology, Department of Anatomy , Royal College of Surgeons in Ireland , Dublin , Ireland
| | - Barbara M Ryan
- c Department of Gastroenterology and Clinical Medicine , Tallaght Hospital and Trinity College , Dublin , Ireland
| | - Zebunnissa Ramtoola
- b School of Pharmacy, Royal College of Surgeons in Ireland , Dublin , Ireland
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22
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Ma C, Ascoytia C, McCarrier KP, Martin M, Feagan BG, Jairath V. Physicians' Perspectives on Cost, Safety, and Perceived Efficacy Determine Aminosalicylate Use in Crohn's Disease. Dig Dis Sci 2018; 63:2555-2563. [PMID: 29959726 DOI: 10.1007/s10620-018-5181-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 06/22/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Aminosalicylates are the most commonly prescribed therapy in Crohn's disease (CD), despite uncertainty in the evidence to support their efficacy. AIMS To examine physicians' perspectives on aminosalicylate use for CD and explore the discordance between clinical practice and the evidence base. METHODS A qualitative interview study was performed amongst physicians with at least 4 years of independent experience in managing CD patients. Semi-structured telephone interviews were conducted using an exploratory interview guide. Interview transcripts were thematically analyzed to elucidate concepts pertaining to treatment strategies for CD, motivations for prescribing aminosalicylates, perceived benefits and harms of aminosalicylate use, and the relationship between the evidence and real-world prescribing practices. RESULTS A representative sample of thirty physicians from four different countries and multiple practice environments (university/teaching hospitals, public practice, private/community practice, and subspecialty gastroenterology clinics) participated. Nearly all physicians (93.3%, 28/30) reported prescribing aminosalicylates for CD. Aminosalicylates were endorsed as first-line therapy for mild CD by nearly half of participants (13/30, 43.3%). A favorable safety profile, possible efficacy in mild colonic CD, and patient reluctance to step-up to other therapies were primary motivators for aminosalicylate use. Almost half of respondents (46.7%) expressed that the evidence informing aminosalicylate efficacy in CD differed substantially from their own clinical experience. CONCLUSIONS Physicians' beliefs about efficacy in subgroups of CD patients, safety, and patient preferences primarily motivate aminosalicylate prescription in CD. There is a lack of confidence in published clinical trials, and a desire for more robust evidence to inform 5-ASA use in CD.
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Affiliation(s)
- Christopher Ma
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.,Robarts Clinical Trials, Inc., London, ON, Canada
| | - Carla Ascoytia
- Health Research Associates, Inc., Mountlake Terrace, WA, USA
| | | | - Mona Martin
- Health Research Associates, Inc., Mountlake Terrace, WA, USA
| | - Brian G Feagan
- Robarts Clinical Trials, Inc., London, ON, Canada.,Department of Medicine, Western University, London, ON, Canada.,Department of Biostatistics and Epidemiology, Western University, London, ON, Canada
| | - Vipul Jairath
- Robarts Clinical Trials, Inc., London, ON, Canada. .,Department of Medicine, Western University, London, ON, Canada. .,Department of Biostatistics and Epidemiology, Western University, London, ON, Canada.
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Rowan CR, Keegan D, Byrne K, Cullen G, Mulcahy HE, Sheridan J, Ryan EJ, de Vries A, D'Haens G, Doherty GA. Subcutaneous rather than intravenous ustekinumab induction is associated with comparable circulating drug levels and early clinical response: a pilot study. Aliment Pharmacol Ther 2018; 48:333-339. [PMID: 29920697 DOI: 10.1111/apt.14834] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 03/18/2018] [Accepted: 05/14/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Ustekinumab (USK) is licenced for intravenous induction and subcutaneous (S/C) maintenance in Crohn's disease. AIM To evaluate ustekinumab trough concentrations and clinical response with exclusive subcutaneous ustekinumab induction. METHODS Patients with Crohn's disease who initiated treatment with subcutaneous ustekinumab at a single academic centre were included in this pilot study. A dosage of 360 mg ustekinumab was given subcutaneously in divided doses; 180 mg at Week 0, 90 mg at Week 1 and 90 mg at Week 2, with corresponding ustekinumab trough concentrations assessed to Week 8. The primary outcome measures were trough serum ustekinumab levels and clinical remission at Week 8. Secondary outcome measures were trough serum ustekinumab levels at Week 1 & 2 and changes in C-reactive protein, albumin and faecal calprotectin at Week 8. RESULTS Nineteen patients were included. Median Week 8 ustekinumab trough concentrations were 6.1 μg/mL (Inter-quartile range 4-9.8 μg/mL). There was a significant improvement in Harvey Bradshaw index from Week 0 (median HBI 5; interquartile range 2-8) to Week 8 (median HBI 1; interquartile range 0-3) (P = 0.002). C-reactive protein levels did not change significantly but faecal calprotectin improved significantly; median faecal calprotectin at Week 0 was 533 μg/g; at Week 8, it was 278 μg/g (P = 0.038). CONCLUSIONS Ustekinumab trough concentrations are comparable whether ustekinumab induction treatment was administered subcutaneously or intravenously. A significant improvement in symptoms and faecal calprotectin was noted. These results support the use of subcutaneous induction as an alternative if there are barriers to intravenous induction.
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Affiliation(s)
- C R Rowan
- Center for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland
| | - D Keegan
- Center for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland
| | - K Byrne
- Center for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland
| | - G Cullen
- Center for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland
| | - H E Mulcahy
- Center for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland
| | - J Sheridan
- Center for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland
| | - E J Ryan
- Center for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland
| | - A de Vries
- Sanquin Diagnostic Services, Amsterdam, The Netherlands
| | - G D'Haens
- Department of Gastroenterology, Amsterdam Medical Centre, Amsterdam, The Netherlands
| | - G A Doherty
- Center for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland
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Anti-TNF Therapy in Crohn's Disease. Int J Mol Sci 2018; 19:ijms19082244. [PMID: 30065229 PMCID: PMC6121417 DOI: 10.3390/ijms19082244] [Citation(s) in RCA: 173] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 07/04/2018] [Accepted: 07/07/2018] [Indexed: 02/06/2023] Open
Abstract
Crohn’s disease (CD) accounts for a variety of clinical manifestations or phenotypes that stem from chronic inflammation in the gastrointestinal tract. Its worldwide incidence is increasing including younger or childhood-onset of disease. The natural history of Crohn’s disease is characterized by a remitting and relapsing course that progresses to complications and surgery in most patients. The goals of treatment are to achieve clinical and endoscopic remission, to avoid disease progression and minimise surgical resections. Medical treatment usually features antibiotics, corticosteroids, immunomodulators (thiopurines, methotrexate). Anti-TNF (tumour necrosis factor) therapy was approved for use in Crohn’s disease in 1998, and has changed the paradigm of treatment, leading to improved rates of response and remission in patients. There are significant considerations that need to be borne in mind, when treating patients including immunogenicity, safety profile and duration of treatment.
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25
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Chronisch-entzündliche Darmerkrankungen. Radiologe 2018; 58:320-325. [DOI: 10.1007/s00117-018-0375-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Explaining Interpatient Variability in Adalimumab Pharmacokinetics in Patients With Crohn's Disease. Ther Drug Monit 2018. [DOI: 10.1097/ftd.0000000000000494] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Tsui JJ, Huynh HQ. Is top-down therapy a more effective alternative to conventional step-up therapy for Crohn's disease? Ann Gastroenterol 2018; 31:413-424. [PMID: 29991886 PMCID: PMC6033752 DOI: 10.20524/aog.2018.0253] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 02/02/2018] [Indexed: 12/17/2022] Open
Abstract
The management of Crohn's disease involves immunosuppressive protocols in a step-up approach that progresses through a therapeutic pyramid with several tiers of medication. Medications at the top are considered more potent but present greater risk. A new top-down approach to therapy inverts this procedure, using top-tier drugs for initial treatment. A critical appraisal of the current literature relating to top-down therapy was performed to evaluate its merit. A literature search was conducted on PubMed, Ovid, and PubMed Central to identify studies of the efficacy of top-down therapy. Papers were appraised critically using the Scottish Intercollegiate Guidelines Network score to evaluate current evidence for the use of top-down therapy. Nineteen studies were identified, including six randomized controlled trials, thirteen cohort studies, and two cost-benefit studies. Early combined therapy involving both biologics and immunomodulators was found to be effective at improving patient outcomes; however, early biologics alone were not shown to have a clear benefit over step-up therapy. Likewise, the early use of immunomodulators alone showed inconsistent results with respect to efficacy in terms of both remission and surgical outcomes. Evidence for application in pediatric populations was also inconclusive. The cost-benefit analyses found that top-down therapy merits investigation, as it proved to be economical given current data. Top-down therapy has the potential of being a viable alternative to step-up therapy, but further studies are needed to determine the most appropriate patients to receive this treatment.
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Affiliation(s)
- Jonathan Jenkin Tsui
- Edinburgh Medical School, University of Edinburgh, Edinburgh, UK (Jonathan Jenkin Tsui)
| | - Hien Q Huynh
- Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada (Hien Q. Huynh)
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Abstract
BACKGROUND Identifying patients with Crohn's disease with rapid disease progress or high risk of early surgery is crucial to clinical decision making. OBJECTIVE The aim was to evaluate the correlation between the Lémann index at diagnosis and abdominal surgery in the first year after Crohn's disease diagnosis and to find the risk factors for early surgery. DESIGN This was a retrospective cohort study. SETTINGS The study was conducted at a single tertiary hospital. PATIENTS Patients diagnosed with Crohn's disease between 2013 and 2015 in our center were included. MAIN OUTCOME MEASURES The outcome of interest was the need for an abdominal surgery within 1 year after the Lémann index evaluation at diagnosis. RESULTS Of 212 eligible patients, 48 patients underwent abdominal surgery during follow-up. Lémann index was much higher in the surgery group (5.3 vs 2.6; p < 0.001). On tertiles of the Lémann index, the frequency of surgery grew (2.8%, 9.9%, and 55.7%; p < 0.001) as the Lémann index increased. The receiver operating characteristic curve was constructed taking into account the Lémann index for selecting patients with a high risk of surgery. Specificity, sensitivity, and area under receiver operating characteristic curve were 84.8%, 81.3%, and 0.89 of the Lémann Index at a cutoff level of 3.7. Patients with Lémann index ≥3.7 carried a higher risk of abdominal surgery (OR = 18.6; p < 0.001). Stricturing and penetrating disease were predictors for abdominal surgery, whereas antitumor necrosis factor treatment was associated with a significant reduction of surgical requirements. LIMITATIONS This study was limited by its retrospective design. The ability of the Lémann index to predict the long-term risk of surgery was unknown. CONCLUSIONS Lémann index at diagnosis is a reliable index to predict the risk of abdominal surgery in the first year after diagnosis of Crohn's disease. Patients with a high Lémann index might need closer follow-up or aggressive medical therapy. See Video Abstract at http://links.lww.com/DCR/A518.
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29
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IL26 modulates cytokine response and anti-TNF consumption in Crohn’s disease patients with bacterial DNA. J Mol Med (Berl) 2017; 95:1227-1236. [DOI: 10.1007/s00109-017-1585-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 08/01/2017] [Accepted: 08/20/2017] [Indexed: 02/07/2023]
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30
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Oh EH, Oh K, Han M, Seo H, Chang K, Lee SH, Kim GU, Song EM, Seo M, Lee HS, Hwang SW, Park SH, Yang DH, Kim KJ, Byeon JS, Myung SJ, Yang SK, Ye BD. Early anti-TNF/immunomodulator therapy is associated with better long-term clinical outcomes in Asian patients with Crohn's disease with poor prognostic factors. PLoS One 2017; 12:e0177479. [PMID: 28542298 PMCID: PMC5441601 DOI: 10.1371/journal.pone.0177479] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 04/27/2017] [Indexed: 11/24/2022] Open
Abstract
Although early treatment of Crohn’s disease (CD) patients with anti-tumor necrosis factor (TNF) agents or immunomodulators (IMs) may improve long-term outcomes, especially those with poor prognostic factors, their effectiveness in Asians remains unclear. In this study, Korean patients with CD naïve to both intestinal surgery and intestinal complications, and with at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) were retrospectively analyzed. Patients were classified into those who started anti-TNFs, or IMs but not anti-TNFs, within 2 years of diagnosis, and those who started anti-TNFs and/or IMs later. Their probabilities of intestinal surgery and intestinal complications were compared. A total of 670 patients were enrolled, 79 in the early anti-TNF, 286 in the early IM, and 305 in the late treatment group. Kaplan-Meier analysis with the log-rank test showed that from starting anti-TNFs/IMs, times to intestinal surgery (P < 0.001), stricturing complications (P = 0.002), and penetrating complications (P < 0.001) were significantly longer in the early anti-TNF/IM groups than in the late treatment group. Multivariate Cox regression analysis showed that, from starting anti-TNFs/IMs, late anti-TNF/IM treatment was independently associated with higher risks of intestinal surgery (adjusted hazard ratio [aHR] 2.321, 95% confidence interval [CI] 1.503–3.584, P < 0.001), behavioral progression (aHR 2.001, 95% CI 1.449–2.763, P < 0.001), stricturing complications (aHR 1.736, 95% CI 1.209–2.493, P = 0.003), and penetrating complications (aHR 3.315, 95% CI 2.094–5.249, P < 0.001) than early treatment. In conclusion, treatment of Asian CD patients having poor prognostic factors with anti-TNFs/IMs within 2 years of diagnosis is associated with better clinical outcomes than later treatment.
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Affiliation(s)
- Eun Hye Oh
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kyunghwan Oh
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Minkyu Han
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyungil Seo
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kiju Chang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sun-Ho Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Gwang-Un Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Eun Mi Song
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Myeongsook Seo
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Ho-Su Lee
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sung Wook Hwang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kyung-Jo Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
- * E-mail:
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Hirschmann S, Neurath MF. Top-down approach to biological therapy of Crohn's disease. Expert Opin Biol Ther 2017; 17:285-293. [PMID: 28132526 DOI: 10.1080/14712598.2017.1287170] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Crohn's disease (CD) is a chronic, immune-mediated condition with a potentially disabling and destructive course. Despite growing data on when to use a therapeutic 'top-down' strategy, clinical management of this complex disorder is still challenging. Currently, the discussion of 'top-down' strategy in CD mostly includes biological therapy alone or in combination. Areas covered: This article is based on a review of existing literature regarding the use of biological therapy in a 'top-down' approach for the treatment of Crohn's disease. The authors reviewed all the major databases including MEDLINE as well as DDW and ECCO abstracts, respectively. Expert opinion: A 'top-down' therapeutic approach in Crohn's disease is strongly supported by existing data in patients with several risk factors for a severe course of disease. Moreover, there is an increasing amount of published data recommending a more individualised therapeutic strategy to identify candidates for 'top-down' treatment, based on enhanced diagnostics using biomarkers. Emerging therapeutic approaches besides existing therapy concepts using biologicals may possibly redefine the 'top-down' therapeutic strategy for Crohn's disease in the future.
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Affiliation(s)
- Simon Hirschmann
- a Medical Clinic 1, Department of Medicine , University Hospital Erlangen, University of Erlangen-Nürnberg , Erlangen , Germany
| | - Markus F Neurath
- a Medical Clinic 1, Department of Medicine , University Hospital Erlangen, University of Erlangen-Nürnberg , Erlangen , Germany
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The Efficacy of Infliximab Monotherapy versus Infliximab-Azathioprine Sequential Treatment in Crohn's Disease: Experience from a Tertiary Medical Center in China. BIOMED RESEARCH INTERNATIONAL 2016; 2016:8648307. [PMID: 27896276 PMCID: PMC5118525 DOI: 10.1155/2016/8648307] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Revised: 10/01/2016] [Accepted: 10/09/2016] [Indexed: 02/08/2023]
Abstract
Objective. To evaluate the efficacy of infliximab (IFX) monotherapy versus infliximab-azathioprine sequential treatment in Crohn's disease (CD) patients. Methods. Patients newly diagnosed with CD using IFX as induction therapy were enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy group and IFX-AZA sequential therapy group. Clinical remission rates were assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were assessed at weeks 84 and 138 to evaluate the efficacy of these two groups. Results. A total of seventy-nine patients had accomplished 138-week follow-up. At weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy group was significantly higher compared to IFX-AZA sequential therapy group (26/57 and 21/57) (P = 0.004 and 0.001, resp.). Similar findings were found in complete endoscopic remission rate. The clinical remission rates of IFX monotherapy group were similar to that of IFX-AZA sequential therapy group (P > 0.05). At weeks 84 and 138, the endoscopic remission rate and the endoscopic improvement rate between these two groups displayed no significant difference (P > 0.05). Conclusion. IFX monotherapy provides higher deep remission rate compared with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who could not receive prolonged IFX therapy, IFX-AZA sequential therapy is acceptable, though long-term efficacy remains to be seen.
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Leitner GC, Vogelsang H. Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World J Gastrointest Pharmacol Ther 2016; 7:5-20. [PMID: 26855808 PMCID: PMC4734954 DOI: 10.4292/wjgpt.v7.i1.5] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 12/14/2015] [Accepted: 01/08/2016] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.
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Khanna R, Bressler B, Levesque BG, Zou G, Stitt LW, Greenberg GR, Panaccione R, Bitton A, Paré P, Vermeire S, D'Haens G, MacIntosh D, Sandborn WJ, Donner A, Vandervoort MK, Morris JC, Feagan BG. Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial. Lancet 2015; 386:1825-34. [PMID: 26342731 DOI: 10.1016/s0140-6736(15)00068-9] [Citation(s) in RCA: 330] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. METHODS In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤ 4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. FINDINGS This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% [SD 14·0] and 61·9% [16·9]; adjusted difference 2·5%, 95% CI -5·2% to 10·2%, p=0·5169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (27·7% and 35·1%, absolute difference [AD] 7·3%, hazard ratio [HR]: 0·73, 95% CI 0·62 to 0·86, p=0·0003). There were no differences in serious drug-related adverse events. INTERPRETATION Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. FUNDING AbbVie Pharmaceuticals.
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Affiliation(s)
- Reena Khanna
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada; Department of Medicine, University of Western Ontario, London, ON, Canada
| | - Brian Bressler
- Department of Gastroenterology, St Paul's Hospital, Vancouver, BC, Canada
| | - Barrett G Levesque
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada; Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - Guangyong Zou
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada; Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada
| | - Larry W Stitt
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada
| | | | - Remo Panaccione
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Alain Bitton
- Division of Gastroenterology, McGill University Health Centre, McGill University, Montreal, QC, Canada
| | - Pierre Paré
- Laval University, CHAUQ, Hôpital du St-Sacrement, Quebec City, QC, Canada
| | - Séverine Vermeire
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Leuven, Belgium
| | - Geert D'Haens
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada; Department of Gastroenterology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Donald MacIntosh
- Division of Gastroenterology, Dalhousie University, Halifax, NS, Canada
| | - William J Sandborn
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada; Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - Allan Donner
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada; Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada
| | | | - Joan C Morris
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada
| | - Brian G Feagan
- Robarts Clinical Trials Inc, Robarts Research Institute, London, ON, Canada; Department of Medicine, University of Western Ontario, London, ON, Canada; Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada.
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Helicobacter pylori-specific protection against inflammatory bowel disease requires the NLRP3 inflammasome and IL-18. Inflamm Bowel Dis 2015; 21:854-61. [PMID: 25742401 DOI: 10.1097/mib.0000000000000318] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The Gram-negative bacterium Helicobacter pylori is a constituent of the human gastric microbiota. Chronic infection with H. pylori causes gastritis and predisposes to gastric carcinoma but has also been inversely linked to various allergic and chronic inflammatory conditions. In particular, large meta-analyses have documented an inverse association between H. pylori infection and the risk of developing ulcerative colitis and Crohn's disease. METHODS We investigated possible protective effects of experimental H. pylori infection and of regular treatment with H. pylori extract in 2 mouse models of colitis and in mouse models of type I diabetes and multiple sclerosis. The mechanism of protection was examined in mouse strains lacking specific innate immune recognition pathways and cytokines. RESULTS We show here that experimental infection with H. pylori and administration of regular doses of H. pylori extract both alleviate the clinical and histopathological features of dextran sodium sulfate-induced chronic colitis and of T-cell transfer-induced colitis. High resolution endoscopy of the protected animals revealed the accumulation of large amounts of colonic mucus upon H. pylori exposure, which could be attributed to transcriptional activation of the mucin 2 gene. The protection against dextran sodium sulfate-induced colitis was dependent on the NLRP3 inflammasome and interleukin-18 signaling. Other autoimmune diseases, i.e., experimental autoimmune encephalomyelitis and type I diabetes, were not controlled by H. pylori. CONCLUSIONS In summary, we propose here that the immunomodulatory activity of an ancient constituent of the gut microbiota, H. pylori, may be exploited for the prevention and/or treatment of inflammatory bowel diseases.
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Smart C, Selinger CP. The cost–effectiveness of infliximab in Crohn’s disease. Expert Rev Pharmacoecon Outcomes Res 2014; 14:589-98. [DOI: 10.1586/14737167.2014.950235] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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