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Bastida Paz G, Merino Ochoa O, Aguas Peris M, Barreiro-de Acosta M, Zabana Y, Ginard Vicens D, Ceballos Santos D, Muñoz Núñez F, Monfort I Miquel D, Catalán-Serra I, García Sánchez V, Loras Alastruey C, Lucendo Villarín A, Huguet JM, de la Coba Ortiz C, Aldeguer Manté X, Palau Canós A, Domènech Morral E, Nos P. The Risk of Developing Disabling Crohn's Disease: Validation of a Clinical Prediction Rule to Improve Treatment Decision Making. Dig Dis 2023; 41:879-889. [PMID: 37611561 DOI: 10.1159/000531789] [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: 12/19/2022] [Accepted: 06/20/2023] [Indexed: 08/25/2023]
Abstract
BACKGROUND Crohn's disease (CD) is characterized by the development of complications over the course of the disease. It is crucial to identify predictive factors of disabling disease, in order to target patients for early intervention. We evaluated risk factors of disabling CD and developed a prognostic model. METHODS In total, 511 CD patients were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to identify demographic, clinical, and biological risk factors. A predictive nomogram model was developed in a subgroup of patients with noncomplicated CD (inflammatory pattern and no perianal disease). RESULTS The rate of disabling CD within 5 years after diagnosis was 74.6%. Disabling disease was associated with gender, location of disease, requirement of steroids for the first flare, and perianal lesions. In the subgroup of patients (310) with noncomplicated CD, the rate of disabling CD was 80%. In the multivariate analysis age at onset <40 years (OR = 3.46, 95% confidence interval [CI] = 1.52-7.90), extensive disease (L3/L4) (OR = 2.67, 95% CI = 1.18-6.06), smoking habit (OR = 2.09, 95% CI = 1.03-4.27), requirement of steroids at the first flare (OR = 2.20, 95% CI = 1.09-4.45), and albumin (OR = 0.59, 95% CI = 0.36-0.96) were associated with development of disabling disease. The developed predictive nomogram based on these factors presented good discrimination, with an area under the receiver operating characteristic curve of 0.723 (95% CI: 0.670-0.830). CONCLUSION We identified predictive factors of disabling CD and developed an easy-to-use prognostic model that may be used in clinical practice to help identify patients at high risk and address treatment effectively.
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Affiliation(s)
- Guillermo Bastida Paz
- Department of Gastroenterology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Olga Merino Ochoa
- Gastroenterology, Hospital Universitario de Cruces, Barakaldo, Spain
| | - Mariam Aguas Peris
- Department of Gastroenterology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | | | - Yamile Zabana
- Gastroenterology Department, Fundació per la Recerca Mútua Terrassa, Hospital Universitari Mútua Terrassa, Terrassa, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | | | | | - Fernando Muñoz Núñez
- University Hospital of Salamanca, Salamanca, Spain
- Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain
| | | | - Ignacio Catalán-Serra
- Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
- Centre of Molecular Inflammation Research (CEMIR) and Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | | | - Carmen Loras Alastruey
- Gastroenterology Department, Fundació per la Recerca Mútua Terrassa, Hospital Universitari Mútua Terrassa, Terrassa, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | | | | | | | | | | | - Eugeni Domènech Morral
- Hospital Universitari Germans Trias i Pujol, Badalona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Pilar Nos
- Department of Gastroenterology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
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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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3
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Frei R, Fournier N, Zeitz J, Scharl M, Morell B, Greuter T, Schreiner P, Misselwitz B, Safroneeva E, Schoepfer AM, Vavricka SR, Rogler G, Biedermann L. Early Initiation of Anti-TNF is Associated with Favourable Long-term Outcome in Crohn's Disease: 10-Year-Follow-up Data from the Swiss IBD Cohort Study. J Crohns Colitis 2019; 13:1292-1301. [PMID: 30854548 DOI: 10.1093/ecco-jcc/jjz057] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 02/28/2019] [Accepted: 03/06/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The optimal timing of treatment escalation in Crohn's disease [CD] remains a challenging issue, and very little is known about its long-term development following early versus late administration of anti-TNF antibodies. The long-term outcome of Swiss CD patients was comparatively assessed in an up to 10-year follow-up, using patients participating in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS]. METHODS Prospectively collected SIBDCS patient data, including disease history, baseline characteristics at enrolment, and course of disease, were analysed in patients with early versus late [<24 versus ≥24 months after diagnosis] and no anti-TNF treatment. RESULTS A reduced risk of developing bowel stenosis was found in patients who received early anti-TNF treatment. This association was seen in patients overall and also in the subgroups of CD patients without pre-existing complications [Log-rank test: p < 0.001].Furthermore, osteoporosis and anaemia were observed significantly less frequently in patients who received early anti-TNF treatment, compared with either patients who received treatment late [p < 0.001 and p = 0.046, respectively] or were never [p < 0.001 for both] treated with anti-TNF antibodies. Patients with early anti-TNF administration sought medical consultations significantly less often, including gastroenterologists in private practice [p = 0.017], ambulatory [outpatient] hospital visits [p = 0.038], and a composite of any medical visits [p = 0.001]. The percentage of patients unable to work was lowest for early-anti-TNF-treated patients, in comparison with patients who were treated late or never [3.6% vs 8.8% vs 3.7%, p = 0.016]. CONCLUSIONS In CD patients within the SIBDCS, early anti-TNF administration was found to be associated with several indicators of a more favourable long-term outcome.
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Affiliation(s)
- Roy Frei
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Nicolas Fournier
- Institute of Social and Preventive Medicine [IUMSP], Lausanne University Hospital, Lausanne, Switzerland
| | - Jonas Zeitz
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland.,Center of Gastroenterology, Clinic Hirslanden, Zurich, Switzerland
| | - Michael Scharl
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Bernhard Morell
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Thomas Greuter
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Benjamin Misselwitz
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Ekaterina Safroneeva
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Alain M Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois [CHUV] and University of Lausanne, Lausanne, Switzerland
| | - Stephan R Vavricka
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland.,Center of Gastroenterology and Hepatology, Zurich, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
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4
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Abstract
Inflammatory bowel disease has become a growing concern worldwide. The chronic and progressive nature of inflammatory bowel disease poses significant challenges to the treatment and management of affected patients, straining health care resources. Therapeutic options and optimal management strategies have evolved dramatically. The treat-to-target strategy has shifted focus toward identifiable and attainable treatment targets and with the ability to optimize tight control. Advancements in our understanding of the pathophysiology led to therapeutic mechanisms that have a more narrowed focus toward gut-specific targets, improving safety profiles.
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Affiliation(s)
- Derrick D Eichele
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-2000, USA.
| | - Renee Young
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-2000, USA
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5
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Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, Makharia GK, Pisespongsa P, Chen MH, Ran ZH, Ye BD, Park DI, Ling KL, Ong D, Ahuja V, Goh KL, Sollano J, Lim WC, Leung WK, Ali RAR, Wu DC, Ong E, Mustaffa N, Limsrivilai J, Hisamatsu T, Yang SK, Ouyang Q, Geary R, De Silva JH, Rerknimitr R, Simadibrata M, Abdullah M, Leong RWL. Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia. J Gastroenterol Hepatol 2019; 34:1296-1315. [PMID: 30848854 DOI: 10.1111/jgh.14648] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/05/2019] [Accepted: 03/02/2019] [Indexed: 02/05/2023]
Abstract
The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
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Affiliation(s)
- Choon Jin Ooi
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.,Duke-NUS Medical School, Singapore
| | - Ida Hilmi
- Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, New Delhi, India
| | | | - Siew Chien Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | | | - Min Hu Chen
- Division of Gastroenterology, The First University Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhi Hua Ran
- Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Byong Duk Ye
- Department of Gastroenterology and IBD Center, University of Ulsan College of Medicine, Ulsan, Korea
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | - David Ong
- Division of Gastroenterology & Hepatology, University Medicine Cluster, National University Hospital of Singapore, Singapore
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Khean Lee Goh
- University of Malaya Specialist Centre, Kuala Lumpur, Malaysia
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Wee Chian Lim
- Department of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore
| | - Wai Keung Leung
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Hong Kong, Hong Kong
| | | | - Deng Chyang Wu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Evan Ong
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Nazri Mustaffa
- Department of Internal Medicine, School of Medical Sciences, Health Campus, Universiti Sains, George Town, Malaysia
| | - Julajak Limsrivilai
- Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan
| | - Suk Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Ulsan, Korea
| | - Qin Ouyang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Richard Geary
- Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand
| | | | | | - Marcellus Simadibrata
- Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia
| | - Murdani Abdullah
- Division of Gastroenterology, Department of Internal Medicine, Dr Cipto Mangankusumo National Hospital, Central Jakarta, Indonesia
| | - Rupert W L Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia
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6
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Beilman CL, Kirwin E, Ma C, McCabe C, Fedorak RN, Halloran B. Early Initiation of Tumor Necrosis Factor Antagonist-Based Therapy for Patients With Crohn's Disease Reduces Costs Compared With Late Initiation. Clin Gastroenterol Hepatol 2019; 17:1515-1524.e4. [PMID: 30056180 DOI: 10.1016/j.cgh.2018.07.032] [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] [Received: 10/02/2017] [Revised: 07/16/2018] [Accepted: 07/18/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Antagonists of tumor necrosis factor (TNF) are effective for induction and maintenance of remission of Crohn's disease (CD) and are generally prescribed when patients do not respond to conventional, less-costly medical therapies. Early initiation of anti-TNF therapy reduced rates of surgery and dose escalation due to loss of response. However, these drugs are expensive, so studies are needed on the cost effectiveness of early initiation. We aimed to determine the cost effectiveness of initiating treatment early in the disease course (within 2 years of CD diagnosis) vs later in the disease course (more than 2 years after diagnosis). METHODS We constructed a Markov model of a hypothetical cohort of patients with CD in Canada to simulate disease progression after initiation of infliximab or adalimumab therapy. We used published loss-of-response rates to compare the lifetime cost effectiveness of early vs late initiation of anti-TNF therapies. Transition probabilities and utilities were obtained through a literature search, and costs were obtained from the Alberta Ministry of Health. Sensitivity analysis was used to characterize uncertainty. RESULTS Early initiation of infliximab yielded an additional 0.72 quality-adjusted life-years (QALYs) and saved $50,418 compared with late initiation. Early initiation of adalimumab yielded an additional 0.54 QALYs and saved $43,969. At a willingness-to-pay threshold of $50,000, early initiations of infliximab or adalimumab therapy had a 74% chance of being cost effective compared with late initiation. CONCLUSIONS In a Markov model analysis, we found initiation of either infliximab or adalimumab within 2 years of CD diagnosis to provide significant cost savings and QALYs compared with later initiation (more than 2 years after diagnosis).
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Affiliation(s)
- Candace L Beilman
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | | | - Christopher Ma
- Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Christopher McCabe
- Department of Emergency Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Richard N Fedorak
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - Brendan Halloran
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
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7
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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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8
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Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, Makharia GK, Pisespongsa P, Chen MH, Ran ZH, Ye BD, Park DI, Ling KL, Ong D, Ahuja V, Goh KL, Sollano J, Lim WC, Leung WK, Ali RAR, Wu DC, Ong E, Mustaffa N, Limsrivilai J, Hisamatsu T, Yang SK, Ouyang Q, Geary R, De Silva JH, Rerknimitr R, Simadibrata M, Abdullah M, Leong RW. Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia. Intest Res 2019; 17:285-310. [PMID: 31146509 PMCID: PMC6667368 DOI: 10.5217/ir.2019.00026] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 04/15/2019] [Indexed: 02/07/2023] Open
Abstract
The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn’s and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn’s disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
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Affiliation(s)
- Choon Jin Ooi
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | | | - Rupa Banerjee
- Asian Institute of Gastroenterology, New Delhi, India
| | | | - Siew Chien Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pises Pisespongsa
- Gastroenterology and Hepatology, Bumrungrad International University, Bangkok, Thailand
| | - Min Hu Chen
- Division of Gastroenterology, The First University Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhi Hua Ran
- Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Byong Duk Ye
- Department of Gastroenterology and IBD Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | - David Ong
- Division of Gastroenterology and Hepatology, National University Hospital of Singapore, University Medicine Cluster, Singapore
| | - Vineet Ahuja
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Khean Lee Goh
- University of Malaya Specialist Centre, Kuala Lumpur, Malaysia
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Wee Chian Lim
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore
| | - Wai Keung Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Hong Kong
| | - Raja Affendi Raja Ali
- Faculty of Medicine, UKM Medical and Specialist Centres, The National University of Malaysia, Kuala Lumpur, Malaysia
| | - Deng Chyang Wu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Evan Ong
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Nazri Mustaffa
- Department of Internal Medicine, School of Medical Sciences, Health Campus, Sains University, Kubang Kerian, Malaysia
| | - Julajak Limsrivilai
- Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan
| | - Suk Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea
| | - Qin Ouyang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Richard Geary
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | | | | | - Marcellus Simadibrata
- Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Murdani Abdullah
- Division of Gastroenterology, Department of Internal Medicine, Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Rupert Wl Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, Australia
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- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
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Günay S, Taşova F, Yılmaz HE, Paköz ZB, Çekiç C. Serum Resolvin E1 Levels and Its Relationship with Disease Activity in Ulcerative Colitis. Gastroenterol Res Pract 2019; 2019:6258327. [PMID: 30906319 PMCID: PMC6393930 DOI: 10.1155/2019/6258327] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 01/08/2019] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Resolvins originate from ω-3 PUFA (polyunsaturated fatty acid) precursors and play a role in the resolution of inflammation. The aim of this study was to determine the serum Resolvin E1 levels in patients with ulcerative colitis (UC) and to evaluate the relationship between the serum Resolvin E1 levels and ulcerative colitis disease activity. METHODS In this observational study, serum samples were collected from 51 patients with UC and 30 healthy controls for the determination of Resolvin E1 levels. Firstly, we compared the serum Resolvin E1 levels between the UC patients and the control group. Subsequently, Resolvin E1 levels were analyzed in patients with active UC and UC in remission. Finally, the correlation between Resolvin E1 and C-reactive protein (CRP) and partial Mayo score (p-MS) was analyzed to determine the efficacy of Resolvin E1 in predicting disease activity. RESULTS Serum Resolvin E1 level was determined in the UC group (3126 ± 1413 ng/ml) and in the control group (2758 ± 1065 ng/ml) (p = 0.187). Serum Resolvin E1 levels were determined in patients with active UC (3114 ± 1166 ng/ml) and patients in remission (3132 ± 1520 ng/ml) (p = 0.749). In the UC group, a low-grade positive significant association was found between Resolvin E1 and CRP (r = 0.303, p = 0.031). There was no significant association between Resolvin E1 and partial Mayo score (r = -0.207, p = 0.146). CONCLUSIONS There was no sufficient evidence that Resolvin E1 was an appropriate inflammatory marker to determine disease activity in UC.
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Affiliation(s)
- Süleyman Günay
- Department of Gastroenterology, Katip Çelebi University, Atatürk Education and Research Hospital, İzmir, Turkey
| | - Ferda Taşova
- Department of Internal Medicine, Katip Çelebi University, Atatürk Education and Research Hospital, İzmir, Turkey
| | - Huriye Erbak Yılmaz
- Department of Biochemistry, Katip Çelebi University, Atatürk Education and Research Hospital, İzmir, Turkey
| | - Zehra Betül Paköz
- Department of Gastroenterology, Tepecik Education and Research Hospital, İzmir, Turkey
| | - Cem Çekiç
- Department of Gastroenterology, Katip Çelebi University, Atatürk Education and Research Hospital, İzmir, Turkey
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Deol N, Nguyen TM, Parker CE, Khanna R, Feagan BG, MacDonald JK, Jairath V. Infliximab for induction of remission in Crohn's disease. Hippokratia 2017. [DOI: 10.1002/14651858.cd012623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Navjot Deol
- University of Western Ontario; Department of Medicine; London Ontario Canada
| | - Tran M Nguyen
- Robarts Clinical Trials; Cochrane IBD Group; 100 Dundas Street, Suite 200 London ON Canada
| | - Claire E Parker
- Robarts Clinical Trials; 100 Dundas Street, Suite 200 London ON Canada N6A 5B6
| | - Reena Khanna
- University of Western Ontario; Department of Medicine; London Ontario Canada
| | - Brian G Feagan
- University of Western Ontario; Department of Medicine; London Ontario Canada
- Robarts Clinical Trials; Cochrane IBD Group; 100 Dundas Street, Suite 200 London ON Canada
- University of Western Ontario; Department of Epidemiology and Biostatistics; London ON Canada
| | - John K MacDonald
- University of Western Ontario; Department of Medicine; London Ontario Canada
- Robarts Clinical Trials; Cochrane IBD Group; 100 Dundas Street, Suite 200 London ON Canada
| | - Vipul Jairath
- University of Western Ontario; Department of Medicine; London Ontario Canada
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11
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Regueiro MD, Greer JB, Hanauer SB. Established Management Paradigms in IBD: Treatment Targets and Therapeutic Tools. ACTA ACUST UNITED AC 2016. [DOI: 10.1038/ajgsup.2016.16] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Lin WC, Chen MJ, Chu CH, Wang TE, Wang HY, Shih SC, Chang CW. Crohn's Disease: Specific Concerns in the Elderly. INT J GERONTOL 2016. [DOI: 10.1016/j.ijge.2015.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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14
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Gutiérrez A, Zapater P, Juanola O, Sempere L, García M, Laveda R, Martínez A, Scharl M, González-Navajas JM, Such J, Wiest R, Rogler G, Francés R. Gut Bacterial DNA Translocation is an Independent Risk Factor of Flare at Short Term in Patients With Crohn's Disease. Am J Gastroenterol 2016; 111:529-40. [PMID: 26902226 DOI: 10.1038/ajg.2016.8] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Accepted: 12/03/2015] [Indexed: 02/08/2023]
Abstract
OBJECTIVES We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)<150. The primary end point was time-to-relapse as evaluated by CDAI>150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-α levels and a higher percentage of patients on intensified anti-TNF therapy. CONCLUSIONS BactDNA is an independent risk factor of relapse at 6 months in CD patients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation.
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Affiliation(s)
- Ana Gutiérrez
- Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Alicante, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Pedro Zapater
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Oriol Juanola
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Laura Sempere
- Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Alicante, Spain
| | - Marifé García
- Servicio Digestivo, Hospital Universitario de Elche, Alicante, Spain
| | - Raquel Laveda
- Hospital Clínico Universitario de San Juan, Alicante, Spain
| | | | - Michael Scharl
- Division of Gastroenterology and Hepatology, University Hospital Zìrich, Zìrich, Switzerland
| | | | - José Such
- Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
| | - Reiner Wiest
- Department of Gastroenterology, University Clinic for Visceral Medicine, Inselspital, Bern, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zìrich, Zìrich, Switzerland
| | - Rubén Francés
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan de Alicante, Spain
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Leitner GC, Vogelsang H. Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World J Gastrointest Pharmacol Ther 2016; 7:5-20. [PMID: 26855808 PMCID: PMC4734954 DOI: 10.4292/wjgpt.v7.i1.5] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 12/14/2015] [Accepted: 01/08/2016] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.
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16
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Qiu Y, Mao R, Chen BL, He Y, Zeng ZR, Chen MH. Systematic Review with Meta-analysis of Prospective Studies: Anti-tumour Necrosis Factor for Prevention of Postoperative Crohn's Disease Recurrence. J Crohns Colitis 2015; 9:918-27. [PMID: 26116553 DOI: 10.1093/ecco-jcc/jjv112] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 06/17/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Although promising, the evidence supporting the use of anti-tumour necrosis factor agents [anti-TNFs] in postoperative Crohn's disease [CD] is still based on limited experience. We aimed to conduct a meta-analysis of prospective studies evaluating the efficacy and safety of anti-TNFs for prevention of postoperative recurrence [POR] in CD. METHODS MEDLINE, EMBASE, Web of Science, the Cochrane database and conference proceeding abstracts were searched. The primary outcome measure was the number of patients who developed POR as defined by the primary studies. RESULTS Six prospective studies were included. The rate of endoscopic recurrence [ER] was significantly lower using anti-TNFs [9.2%, 7/76] compared with the non-biologicals group [61.5%, 83/135] (odds ratio [OR] 0.05, 95% confidence interval [CI] 0.02-0.13; p < 0.001]. The rate of severe ER was also lower in the anti-TNFs group [1.6%, 1/64] than that in the non-biologicals group [32.7%, 18/55, OR 0.10; p = 0.04]. A significantly lower proportion of patients in the anti-TNFs group developed clinical recurrence [3.4%, 2/59] compared with the non-biologicals arm [41.1%, 49/119, OR 0.1; p < 0.001]. More anti-TNFs-treated patients [86.5%, 45/52] were maintained in clinical remission compared with the non-biologicals group [58.1%, 43/74, OR 4.05, 95% CI 1.60-10.29; p < 0.01]. The adverse events were similar between the two groups [anti-TNFs 44.9% [22/49] vs control 52.5% [42/80]; p = 0.69]. CONCLUSIONS Anti-TNFs are superior to non-biological agents in preventing endoscopic and clinical recurrence of CD without causing more adverse events.
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Affiliation(s)
- Yun Qiu
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Ren Mao
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Bai-li Chen
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Yao He
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Zhi-rong Zeng
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Min-hu Chen
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China
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Erim DO, Mahendraratnam N, Okafor PN, Wheeler SB. The Value of Vedolizumab as Rescue Therapy in Moderate-Severe Crohn's Disease Patients with Adalimumab Non-response in the USA. J Crohns Colitis 2015; 9:669-75. [PMID: 25987351 DOI: 10.1093/ecco-jcc/jjv090] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 05/12/2015] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS In May 2014, vedolizumab was approved by the Food and Drug Administration for the treatment of moderate-to-severe Crohn's disease. In clinical practice it is typically used in patients who are primary or secondary non-responders to adalimumab [Humira]. We aim to estimate the incremental benefits and costs of using vedolizumab as rescue therapy for adalimumab non-responders. METHODS A Markov model was used to simulate the clinical course of Crohn's disease in a hypothetical cohort of 10,000 patients over a 12-month period. The treatment strategies evaluated were adalimumab only [with and without dose intensification] and adalimumab and vedolizumab [with and without adalimumab dose intensification]. The base case strategy was adalimumab only with 25% of non-responders undergoing dose intensification. Our primary outcomes were changes in costs and quality of life measures over the analytical horizon. RESULTS In a 1-year period, initiating vedolizumab as rescue therapy in adalimumab non-responders reduces the average total cost per patient by 10%, and increases the average amount of time spent in remission or mild disease by up to 2 months. CONCLUSIONS Treating on-label adalimumab non-responders with vedolizumab can, in the short term, significantly improves the quality of life of Crohn's disease patients that do not respond to adalimumab.
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Affiliation(s)
- Daniel O Erim
- Department of Health Policy and Management, Gillings School of Public Health, University of North Carolina, Chapel Hill, NC, USA
| | - Nirosha Mahendraratnam
- Department of Pharmaceutical Outcomes and Policy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
| | - Phillip N Okafor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Stephanie B Wheeler
- Department of Health Policy and Management, Gillings School of Public Health, University of North Carolina, Chapel Hill, NC, USA
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D'Haens GR, Sartor RB, Silverberg MS, Petersson J, Rutgeerts P. Future directions in inflammatory bowel disease management. J Crohns Colitis 2014; 8:726-34. [PMID: 24742736 DOI: 10.1016/j.crohns.2014.02.025] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 02/26/2014] [Accepted: 02/26/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Clinical management of inflammatory bowel diseases (IBD), new treatment modalities and the potential impact of personalised medicine remain topics of intense interest as our understanding of the pathophysiology of IBD expands. METHODS Potential future strategies for IBD management are discussed, based on recent preclinical and clinical research. RESULTS A top-down approach to medical therapy is increasingly being adopted for patients with risk factors for severe inflammation or an unfavourable disease course in an attempt to halt the inflammatory process as early as possible, prevent complications and induce mucosal healing. In the future, biological therapies for IBD are likely to be used more selectively based on personalised benefit/risk assessment, determined through reliable biomarkers and tissue signatures, and will probably be optimised throughout the course of treatment. Biologics with different mechanisms of action will be available; when one drug fails, patients will be able to switch to another and even combination biologics may become a reality. The role of biotherapeutic products that are similar to currently licensed biologics in terms of quality, safety and efficacy - i.e. biosimilars - is at an early stage and requires further experience. Other therapeutic strategies may involve manipulation of the microbiome using antibiotics, probiotics, prebiotics, diet and combinations of all these approaches. Faecal microbiota transplantation is also a potential option in IBD although controlled data are lacking. CONCLUSIONS The future of classifying, prognosticating and managing IBD involves an outcomes-based approach to identify biomarkers reflecting various biological processes that can be matched with clinically important endpoints.
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Affiliation(s)
- Geert R D'Haens
- Department of Gastroenterology, Academic Medical Centre, University of Amsterdam, The Netherlands.
| | - R Balfour Sartor
- Division of Gastroenterology and Hepatology, Multidisciplinary IBD Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Mark S Silverberg
- Mount Sinai Hospital, University of Toronto, ON, Canada; The Zane Cohen Centre for Digestive Diseases, University of Toronto, ON, Canada
| | - Joel Petersson
- Global Medical Affairs Gastroenterology, AbbVie, Rungis, France
| | - Paul Rutgeerts
- Division of Gastroenterology, Department of Internal Medicine, Catholic University of Leuven, Leuven, Belgium
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Bounthavong M, Madkour N, Kazerooni R. Retrospective cohort study of anti-tumor necrosis factor agent use in a veteran population. PeerJ 2014; 2:e385. [PMID: 24883246 PMCID: PMC4034612 DOI: 10.7717/peerj.385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 04/26/2014] [Indexed: 12/05/2022] Open
Abstract
Introduction. Anti-tumor necrosis factor (TNF) agents are effective for several immunologic conditions (rheumatoid arthritis (RA), Crohn’s disease (CD), and psoriasis). The purpose of this study was to evaluate the efficacy and safety of anti-TNF agents via chart review. Methods. Single-site, retrospective cohort study that evaluated the efficacy and safety of anti-TNF agents in veterans initiated between 2010 and 2011. Primary aim evaluated response at 12 months post-index date. Secondary aims evaluated initial response prior to 12 months post-index date and infection events. Results. A majority of patients were prescribed anti-TNF agents for CD (27%) and RA (24%). Patients were initiated on etanercept (41%), adalimumab (40%), and infliximab (18%) between 2010 and 2011. No differences in patient demographics were reported. Response rates were high overall. Sixty-five percent of etanercept patients, 82% of adalimumab patients, and 59% of infliximab patients were either partial or full responders, respectively. Approximately 16%, 11%, and 12% of etanercept, adalimumab, and infliximab were non-responders, respectively. Infections between the groups were non-significant. Etanercept and adalimumab patients had higher but non-significant odds of being a responder relative to infliximab. Conclusions. Most patients initiated with anti-TNF agent were responders at 12 months follow-up for all indications in a veteran population.
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Affiliation(s)
- Mark Bounthavong
- Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
| | - Nermeen Madkour
- Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
| | - Rashid Kazerooni
- Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
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Girolomoni G, Griffiths CEM, Krueger J, Nestle FO, Nicolas JF, Prinz JC, Puig L, Ståhle M, van de Kerkhof PCM, Allez M, Emery P, Paul C. Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper. J DERMATOL TREAT 2014; 26:103-12. [DOI: 10.3109/09546634.2014.880396] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Gutiérrez A, Scharl M, Sempere L, Holler E, Zapater P, Almenta I, González-Navajas JM, Such J, Wiest R, Rogler G, Francés R. Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease. Gut 2014; 63:272-80. [PMID: 23376290 DOI: 10.1136/gutjnl-2012-303557] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The aetiology of Crohn's disease (CD) has been related to nucleotide-binding oligomerisation domain containing 2 (NOD2) and ATG16L1 gene variants. The observation of bacterial DNA translocation in patients with CD led us to hypothesise that this process may be facilitated in patients with NOD2/ATG16L1-variant genotypes, affecting the efficacy of anti-tumour necrosis factor (TNF) therapies. DESIGN 179 patients with Crohn's disease were included. CD-related NOD2 and ATG16L1 variants were genotyped. Phagocytic and bactericidal activities were evaluated in blood neutrophils. Bacterial DNA, TNFα, IFNγ, IL-12p40, free serum infliximab/adalimumab levels and antidrug antibodies were measured. RESULTS Bacterial DNA was found in 44% of patients with active disease versus 23% of patients with remitting disease (p=0.01). A NOD2-variant or ATG16L1-variant genotype was associated with bacterial DNA presence (OR 4.8; 95% CI 1.1 to 13.2; p=0.001; and OR 2.4; 95% CI 1.4 to 4.7; p=0.01, respectively). This OR was 12.6 (95% CI 4.2 to 37.8; p=0.001) for patients with a double-variant genotype. Bacterial DNA was associated with disease activity (OR 2.6; 95% CI 1.3 to 5.4; p=0.005). Single and double-gene variants were not associated with disease activity (p=0.19). Patients with a NOD2-variant genotype showed decreased phagocytic and bactericidal activities in blood neutrophils, increased TNFα levels in response to bacterial DNA and decreased trough levels of free anti-TNFα. The proportion of patients on an intensified biological therapy was significantly higher in the NOD2-variant groups. CONCLUSIONS Our results characterise a subgroup of patients with CD who may require a more aggressive therapy to reduce the extent of inflammation and the risk of relapse.
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Affiliation(s)
- Ana Gutiérrez
- Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, , Alicante, Spain
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Xu Z, Davis HM, Zhou H. Rational development and utilization of antibody-based therapeutic proteins in pediatrics. Pharmacol Ther 2013; 137:225-47. [DOI: 10.1016/j.pharmthera.2012.10.005] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2012] [Accepted: 10/08/2012] [Indexed: 12/15/2022]
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Yoshida K, Fukunaga K, Ikeuchi H, Kamikozuru K, Hida N, Ohda Y, Yokoyama Y, Iimuro M, Takeda N, Kato K, Kikuyama R, Nagase K, Hori K, Nakamura S, Miwa H, Matsumoto T. Scheduled infliximab monotherapy to prevent recurrence of Crohn's disease following ileocolic or ileal resection: a 3-year prospective randomized open trial. Inflamm Bowel Dis 2012; 18:1617-23. [PMID: 22081474 DOI: 10.1002/ibd.21928] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2011] [Accepted: 09/23/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Infliximab (IFX) is effective for remission induction and maintenance of Crohn's disease (CD). This trial assessed the efficacy of scheduled maintenance IFX monotherapy to prevent postoperative CD recurrence. METHODS Thirty-one CD patients who had ileocolic resection within the past 4 weeks were randomly assigned to scheduled IFX at 5 mg/kg intravenously every 8 weeks for 36 months (n = 15) or without IFX (control, n = 16). All patients were treated without immunomodulator or corticosteroid following surgery. The primary and secondary endpoints were remission rates at 12 and 36 months, defined as CD Activity Index (CDAI) ≤150, an International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score <2, and C-reactive protein (CRP) <0.3 mg/dL. Additionally, endoscopic recurrences at 12 and 36 months were evaluated. RESULTS At 12 and 36 months, 100%, and 93.3% of patients in the IFX group were in remission (IOIBD <2), respectively vs. 68.8% and 56.3% in the control arm (P < 0.03). Similarly, 86.7% and 86.7% of patients in the IFX group maintained serological remission (CRP <0.3 mg/dL) vs. 37.5% and 37.5% in the control arm (P < 0.02). Further, the IFX group achieved higher endoscopic remission at 12 months, 78.6% vs. 18.8% (P = 0.004). However, in the Kaplan-Meier survival analysis the CDAI scores between the two arms were not significantly different either at 12 or at 36 months. No adverse event (AE) was observed. CONCLUSIONS An early intervention with IFX monotherapy should prevent clinical, serological, and endoscopic CD recurrence following ileocolic resection. Thiopurine naivety and eliminating the initial loading dose of IFX might minimize serious AEs.
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Affiliation(s)
- Koji Yoshida
- Department of Lower Gastroenterology, Hyogo College of Medicine, Nishinomiya, Japan
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Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol 2012; 107:1409-22. [PMID: 22890223 PMCID: PMC3438468 DOI: 10.1038/ajg.2012.218] [Citation(s) in RCA: 580] [Impact Index Per Article: 44.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The objective of this study was to contribute long-term safety data for infliximab and other therapies in Crohn's disease (CD). METHODS We prospectively evaluated CD patients enrolled in the large, observational Crohn's Therapy, Resource, Evaluation, and Assessment Tool registry, established to compare infliximab safety with conventional nonbiological medications in CD. RESULTS A total of 6,273 patients were enrolled and evaluated on or before 23 February 2010; 3,420 received infliximab (17,712 patient-years; 89.9% received ≥ 2 infusions) and 2,853 received other-treatments-only (13,251 patient-years). Mean length of patient follow-up was 5.2 years. More infliximab- than other-treatments-only-treated patients had moderate-to-severe (30.6% vs. 10.7%) or severe-to-fulminant (2.5% vs. 0.6%) disease severity (P < 0.001). In the year before enrollment, more infliximab- than other-treatments-only-treated patients required surgical intervention (17.4% vs. 13.6%), medical hospitalization (14.2% vs. 8.8%), prednisone (47.8% vs. 31.4%), immunomodulators (52.0% vs. 32.1%), and narcotic analgesics (17.3% vs. 9.1%). Patient mortality was similar for infliximab- and other-treatments-only-treated patients (0.58 vs. 0.59/100 patient-years). In multivariate logistic regression analyses, treatment with prednisone (hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.55, 2.95; P < 0.001) or narcotic analgesics (HR = 1.79, 95% CI = 1.29, 2.48; P < 0.001) and age (HR = 1.08, 95% CI = 1.07, 1.09; P < 0.001) were associated with increased mortality risk. Neither infliximab nor immunomodulator treatment was associated with increased mortality risk. Factors independently associated with serious infections included moderate-to-severe disease activity (HR = 2.24, 95% CI = 1.57, 3.19; P < 0.001), narcotic analgesic treatment (HR = 1.98, 95% CI = 1.44, 2.73; P < 0.001), prednisone therapy (HR = 1.57, 95% CI = 1.17, 2.10; P = 0.002), and infliximab treatment (HR = 1.43, 95% CI = 1.11, 1.84; P = 0.006). CONCLUSIONS Mortality was similar between infliximab- and other-treatments-only-treated CD patients. An increased risk of serious infection with infliximab was observed, although CD severity and use of prednisone or narcotic analgesics carried higher risks.
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Kasparek MS, Bruckmeier A, Beigel F, Müller MH, Brand S, Mansmann U, Jauch KW, Ochsenkühn T, Kreis ME. Infliximab does not affect postoperative complication rates in Crohn's patients undergoing abdominal surgery. Inflamm Bowel Dis 2012; 18:1207-13. [PMID: 21928373 DOI: 10.1002/ibd.21860] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2011] [Accepted: 07/18/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND In patients with Crohn's disease (CD), the effect of anti-tumor necrosis factor alpha (TNF-α) antibody therapy on postoperative complications remains unclear. We aimed to determine the effects of infliximab on postoperative complication rates in patients undergoing abdominal surgery for CD. METHODS Infliximab-treated CD patients undergoing abdominal surgery were identified in a prospective database. Gender- and age-matched CD patients without infliximab treatment served as controls. General and complication-related information was retrieved from patient records. RESULTS Forty-eight patients underwent abdominal surgery within 3 months (median 60 days, range 1-90 days) after infliximab administration (56% female, median age 35 years, range 17-66 years). Forty-eight patients without infliximab served as controls (50% female, 39 [17-68] years). Patient characteristics and number of minor complications were comparable between groups: wound infection (infliximab: 19% vs. controls: 15%), prolonged postoperative ileus (15% vs. 4%), and urinary tract infection (2% vs. 0%; all P > 0.05). No differences were found in major complications: anastomotic leakage (infliximab: 4% vs. controls: 13%), abscess formation (6% vs. 10%), bowel perforation (2% vs. 4%), stoma complication (6% vs. 2%), postoperative hemorrhage (8% vs. 2%), and enterocutaneous fistula (4% vs. 0%; all P > 0.05). One malnourished infliximab-treated patient with a complicated course of disease died postoperatively after anastomotic leakage, sepsis, and cardiac arrhythmia. Eleven infliximab and 10 control patients required reoperation (P > 0.05). Hospital stay was comparable between groups (infliximab: 13 [5-41] vs. controls: 12 [5-54] days; P > 0.05). CONCLUSIONS Infliximab does not affect postoperative complication rates, suggesting no need to alter surgical management in these patients.
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Affiliation(s)
- Michael S Kasparek
- Department of Surgery, Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany
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Johnson LA, Luke A, Sauder K, Moons DS, Horowitz JC, Higgins PD. Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: impact of a "Top-Down" approach to intestinal fibrosis in mice. Inflamm Bowel Dis 2012; 18:460-71. [PMID: 21761511 PMCID: PMC3206985 DOI: 10.1002/ibd.21812] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2011] [Accepted: 06/02/2011] [Indexed: 12/16/2022]
Abstract
BACKGROUND The natural history of Crohn's disease follows a path of progression from an inflammatory to a fibrostenosing disease, with most patients requiring surgical resection of fibrotic strictures. Potent antiinflammatory therapies reduce inflammation but do not appear to alter the natural history of intestinal fibrosis. The aim of this study was to determine the relationship between intestinal inflammation and fibrogenesis and the impact of a very early "top-down" interventional approach on fibrosis in vivo. METHODS In this study we removed the inflammatory stimulus from the Salmonella typhimurium mouse model of intestinal fibrosis by eradicating the S. typhimurium infection with levofloxacin at sequential timepoints during the infection. We evaluated the effect of this elimination of the inflammatory stimulus on the natural history of inflammation and fibrosis as determined by gross pathology, histopathology, mRNA expression, and protein expression. RESULTS Fibrogenesis is preceded by inflammation. Delayed eradication of the inflammatory stimulus by antibiotic treatment represses inflammation without preventing fibrosis. Early intervention significantly ameliorates but does not completely prevent subsequent fibrosis. CONCLUSIONS This study demonstrates that intestinal fibrosis develops despite removal of an inflammatory stimulus and elimination of inflammation. Early intervention ameliorates but does not abolish subsequent fibrosis, suggesting that fibrosis, once initiated, is self-propagating, suggesting that a very early top-down interventional approach may have the most impact on fibrostenosing disease.
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Affiliation(s)
- Laura A. Johnson
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Hospitals, Ann Arbor, MI 48109
| | - Amy Luke
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Hospitals, Ann Arbor, MI 48109
| | - Kay Sauder
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Hospitals, Ann Arbor, MI 48109
| | - David S. Moons
- Department of Pathology, University of Michigan Hospitals, Ann Arbor, MI 48109
| | - Jeffrey C. Horowitz
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Hospitals, Ann Arbor, MI 48109
| | - Peter D.R. Higgins
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Hospitals, Ann Arbor, MI 48109
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Abstract
PURPOSE OF REVIEW The aim of this article is to review current evidence-based approaches to treatment of ulcerative colitis and Crohn's disease. RECENT FINDINGS The primary goal of treatment is to induce and to maintain remission in a safe and efficacious fashion. The 5-aminosalicylic acid (5-ASA) agents and oral steroids remain the first-line approach for the treatment of ulcerative colitis and Crohn's disease. The 'step-up' approach includes the use of immunomodulators [azathioprine (AZA), or 6-mercaptopurine (6-MP)] and newer biologic agents (infliximab, adalimumab, and natalizumab). The 'step-down' approach can also be considered individually on the basis of the severity of Crohn's disease. SUMMARY Current treatment regimens still involve medications with well known efficacy and safety profiles and progress to more potent treatments such as immunomodulators and biologic agents. Adverse events of potent treatment with biologics and immunomodulators have been recognized. In some cases, aggressive approaches with the use of more potent agents as first-line therapy has been proposed, but they are still not considered a routine approach.
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Lee TW, Fedorak RN. Tumor necrosis factor-α monoclonal antibodies in the treatment of inflammatory bowel disease: clinical practice pharmacology. Gastroenterol Clin North Am 2010; 39:543-57. [PMID: 20951917 DOI: 10.1016/j.gtc.2010.08.018] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
In the last 10 years, anti-tumor necrosis factor (TNF)-α therapy has become a cornerstone in the management of autoimmune diseases. Clinical trial data have consistently found that infliximab, adalimumab, and recently certolizumab pegol offer therapeutic benefits to patients with inflammatory bowel diseases (Crohn's disease and ulcerative colitis). Recent understanding on how these monoclonal antibodies evoke changes at the physiological and molecular levels have provided insights into disease pathogenesis and helped to identify new targets for future drug therapy. With increased experience in the use of these anti-TNF-α antibodies the long-term safety data, use in pregnancy have become available. This article provides an overview of the current knowledge regarding anti-TNF-α therapies for clinicians caring for patients with Crohn's disease and ulcerative colitis.
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Affiliation(s)
- Thomas W Lee
- Division of Gastroenterology, University of Alberta, 2-14A Zeidler Building, Edmonton, AB T6G 2X8, Canada
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