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Rabinowitz LG, Gade A, Feuerstein JD. Medical management of acute severe ulcerative colitis in the hospitalized patient. Expert Rev Gastroenterol Hepatol 2025:1-14. [PMID: 40187895 DOI: 10.1080/17474124.2025.2488884] [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] [Received: 11/25/2024] [Accepted: 04/01/2025] [Indexed: 04/07/2025]
Abstract
INTRODUCTION Approximately one in every four patients with ulcerative colitis will develop acute severe ulcerative colitis (ASUC). Historically, this was managed with intravenous steroids and surgery when steroids failed. The use of rescue therapy. AREAS COVERED This review summarizes the latest research in the management of hospitalized patients with ASUC. Covering the historical data and success of rescue therapy with cyclosporine and then with infliximab changed outcomes and reduced the risk of colectomy during the hospitalization and at 1 year. More recently, more biologics and small molecules have been approved and more patients present to the hospital with ASUC already failing anti-tumor necrosis factor antagonists. More recent studies have shown some efficacy of rescue therapy with other classes of biologics (e.g. interleukins and anti-integrins). The more recently approved small molecules (i.e. tofacitinib and Upadacitinib) have shown a rapid onset in therapeutic efficacy in as little as 1 day with sustained response at 1 year in reducing the risk of colectomy following ASUC. EXPERT OPINION In the expert opinion, we discuss the challenges in the treatment of patients with ASUC. We summarize the data of current biologics and new small molecules and their emerging roles in the management of ASUC.
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Affiliation(s)
- Loren G Rabinowitz
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Ajay Gade
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Horio Y, Uchino M, Tomoo Y, Nomura K, Nagano K, Kusunoki K, Kuwahara R, Kimura K, Kataoka K, Beppu N, Ueda T, Ichiki K, Nakajima K, Ikeda M, Ikeuchi H. Oral antimicrobial prophylaxis was associated with preventing surgical site infection following 2-stage restorative proctocolectomy in patients with ulcerative colitis. Tech Coloproctol 2025; 29:83. [PMID: 40121608 PMCID: PMC11930863 DOI: 10.1007/s10151-025-03126-2] [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: 08/19/2024] [Accepted: 02/23/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND Surgical site infection (SSI) is a critical issue in colorectal surgery because it decreases postoperative patient quality of life. The rate of SSI in patients with ulcerative colitis (UC) receiving immunosuppressive therapy is particularly high, suggesting that the SSI rate may increase with the introduction of biologic agents. METHODS UC patients who underwent two-stage restorative proctocolectomy at our institution between April 2012 and December 2023 were included in this study. Clinical characteristics were analyzed and compared between an SSI group and a non-SSI group; possible risk factors for SSIs were also analyzed. Additionally, the following anti-SSI measures adopted at our hospital were included as explanatory variables: laparoscopic surgery, oral antibiotic prophylaxis and change of surgical instruments before wound closure. RESULTS In total, 501 UC surgical patients were included. The incidence of overall SSIs was 45/501 (8.9%). The rates of incisional SSIs and organ/space SSIs were 26/501 (5.1%) and 30/501 (5.9%), respectively. Oral antibiotic prophylaxis was identified as a risk factor for overall SSIs (odds ratio: 0.45, 95% CI 0.20-0.99, p = 0.02), incisional SSIs (odds ratio: 0.34, 95% CI 0.11-1.03, p = 0.03) and organ/space SSIs (odds ratio: 0.35, 95% CI 0.12-0.98, p = 0.04). The use of biologic and immunosuppressive agents was not associated with any SSIs. CONCLUSIONS Nonadministration of oral antibiotic prophylaxis was identified as a risk factor for SSIs. Oral antibiotic prophylaxis before restorative proctocolectomy may improve the postoperative quality of life of UC patients by preventing SSIs.
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Affiliation(s)
- Y Horio
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - M Uchino
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Y Tomoo
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - K Nomura
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - K Nagano
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - K Kusunoki
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - R Kuwahara
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - K Kimura
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - K Kataoka
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - N Beppu
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - T Ueda
- Department of Infection Control and Prevention, Hyogo Medical University, Nishinomiya, Hyogo, 663-8501, Japan
| | - K Ichiki
- Department of Infection Control and Prevention, Hyogo Medical University, Nishinomiya, Hyogo, 663-8501, Japan
| | - K Nakajima
- Department of Infection Control and Prevention, Hyogo Medical University, Nishinomiya, Hyogo, 663-8501, Japan
| | - M Ikeda
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - H Ikeuchi
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
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Gupta A, Erridge S, Graf V, Kelada M, Bapir L, Jesuraj N, Warner-Levy J, Clarke E, McLachlan K, Coomber R, Rucker JJ, Platt MW, Sodergren MH. UK medical cannabis registry: an updated analysis of clinical outcomes of cannabis-based medicinal products for inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2024; 18:829-838. [PMID: 39689344 DOI: 10.1080/17474124.2024.2443574] [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: 08/28/2024] [Revised: 11/26/2024] [Accepted: 12/13/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND Treatments for inflammatory bowel disease (IBD) remain limited, and cannabis-based medicinal products (CBMPs) provide promise in addressing inflammation and pain. However, long-term data on CBMP efficacy in IBD are scarce. This study examines health-related quality of life (HRQoL) changes in IBD patients treated with CBMPs. RESEARCH DESIGN AND METHODS Patients with IBD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in the short IBD questionnaire (SIBDQ), EQ-5D-5L, single-item sleep quality scale (SQS), and generalized anxiety disorder-7 (GAD-7), from baseline to 18-months after CBMP treatment started. Secondary outcomes were adverse event prevalence. RESULTS Analysis of 116 patients with IBD included 94 males (81.03%) with a mean age of 39.52 ± 9.12 years. There were improvements in the SIBDQ, GAD-7, SQS, and EQ-5D-5L Index (p < 0.001). At 18-months, 30 (25.86%) patients achieved a minimal clinically important difference (MCID) in the SIBDQ. Patients with severe baseline anxiety and above-median THC doses were more likely to achieve this MCID (p < 0.050). Twenty (17.24%) patients reported 155 (133.62%) adverse events. CONCLUSIONS CBMP treatment was associated with improvement in IBD-specific outcomes in patients and general HRQoL over 18-months. However, causation cannot be inferred. Hence, randomized controlled trials are still required.
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Affiliation(s)
- Aashray Gupta
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - Simon Erridge
- Medical Cannabis Research Group, Imperial College London, London, UK
- Department of Medicine, Curaleaf Clinic, London, UK
| | - Vivian Graf
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - Monica Kelada
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - Lara Bapir
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - Naveen Jesuraj
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - John Warner-Levy
- Medical Cannabis Research Group, Imperial College London, London, UK
| | | | | | - Ross Coomber
- Department of Medicine, Curaleaf Clinic, London, UK
- Department of Trauma and Orthopaedics, St. George's Hospital NHS Trust, London, UK
| | - James J Rucker
- Department of Medicine, Curaleaf Clinic, London, UK
- Department of Psychological Medicine, Kings College London, London, UK
- Centre for Affective Disorders, South London & Maudsley NHS Foundation Trust, London, UK
| | | | - Mikael H Sodergren
- Medical Cannabis Research Group, Imperial College London, London, UK
- Department of Medicine, Curaleaf Clinic, London, UK
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Buchner AM, Farraye FA, Iacucci M. AGA Clinical Practice Update on Endoscopic Scoring Systems in Inflammatory Bowel Disease: Commentary. Clin Gastroenterol Hepatol 2024; 22:2188-2196. [PMID: 39297813 DOI: 10.1016/j.cgh.2024.06.048] [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: 02/06/2024] [Revised: 06/02/2024] [Accepted: 06/14/2024] [Indexed: 10/27/2024]
Abstract
DESCRIPTION Endoscopic scoring systems evaluate the severity of inflammation and provide objectivity, uniformity, and standardization of reporting of mucosal appearances in patients with inflammatory bowel disease; thus, they have been advised for assessing the efficacy of medical treatment and prognosis. This American Gastroenterological Association (AGA) Clinical Practice Update Expert Commentary aims to review the utilized endoscopic scoring systems and their role in assessing mucosal healing in inflammatory bowel disease and the practical challenges in their applications, as well as to discuss the future of endoscopic scoring systems. METHODS This expert commentary was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. RESULTS/CONCLUSION This expert commentary incorporates essential studies in this field and reflects the authors' expertise in the endoscopic evaluation of inflammatory bowel disease.
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Affiliation(s)
- Anna M Buchner
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.
| | | | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
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Strande V, Lund C, Hagen M, Bengtson MB, Cetinkaya RB, Detlie TE, Frigstad SO, Høie O, Medhus AW, Henriksen M, Aass Holten KI, Hovde Ø, Huppertz-Hauss G, Johansen I, Olsen BC, Opheim R, Ricanek P, Torp R, Tønnessen T, Vatn S, Aabrekk TB, Høivik ML, Kristensen VA. Clinical course of ulcerative colitis: Frequent use of biologics and low colectomy rate first year after diagnosis-results from the IBSEN III inception cohort. Aliment Pharmacol Ther 2024; 60:357-368. [PMID: 38837289 DOI: 10.1111/apt.18097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/16/2024] [Accepted: 05/18/2024] [Indexed: 06/07/2024]
Abstract
BACKGROUND The introduction of biologic therapies and the 'treat-to-target' treatment strategy may have changed the disease course of ulcerative colitis (UC). AIMS To describe the early disease course and disease outcome at 1-year follow-up in a population-based inception cohort of adult patients with newly diagnosed UC. METHODS The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study with prospective follow-up. Patients newly diagnosed with inflammatory bowel disease during 2017-2019 were included. Patients ≥18 years at diagnosis of UC who attended the 1-year follow-up were investigated. We registered clinical, endoscopic and demographic data at diagnosis and 1-year follow-up. RESULTS We included 877 patients with UC (median age 36 years (range: 18-84), 45.8% female). At diagnosis, 39.2% presented with proctitis, 24.7% left-sided colitis and 36.0% extensive colitis. At the 1-year follow-up, 13.9% experienced disease progression, and 14.5% had received one or more biologic therapies. The colectomy rate was 0.9%. Steroid-free clinical remission was observed in 76.6%, and steroid-free endoscopic remission in 68.7%. Anaemia and initiation of systemic steroid treatment at diagnosis were associated with biologic therapy within the first year after diagnosis. CONCLUSION In this population-based inception cohort, colectomy rate in the first year after diagnosis was low, and a high proportion of patients were in remission at 1-year follow-up. The use of biologic therapy increases, consistent with findings from previous studies.
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Affiliation(s)
- Vibeke Strande
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Charlotte Lund
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Public Health, Oslo Metropolitan University, Oslo, Norway
| | - Milada Hagen
- Department of Public Health, Oslo Metropolitan University, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - May-Bente Bengtson
- Department of Gastroenterology, Vestfold Hospital Trust, Tønsberg, Norway
| | | | - Trond Espen Detlie
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Svein Oskar Frigstad
- Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway
| | - Ole Høie
- Department of Internal Medicine, Hospital of Southern Norway, Arendal, Norway
| | - Asle W Medhus
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Magne Henriksen
- Department of Gastroenterology, Østfold Hospital Trust, Sarpsborg, Norway
| | - Kristina I Aass Holten
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Østfold Hospital Trust, Sarpsborg, Norway
| | - Øistein Hovde
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Internal Medicine, Innlandet Hospital Trust, Gjøvik, Norway
| | | | - Ingunn Johansen
- Faculty of Health, Welfare and Org., Østfold University College, Fredrikstad, Norway
- Department of Public Health Science, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Bjørn Christian Olsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Telemark Hospital Trust, Skien, Norway
| | - Randi Opheim
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
- Department of Public Health Science, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Petr Ricanek
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
- Department of Gastroenterology, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Roald Torp
- Department of Internal Medicine, Innlandet Hospital Trust, Hamar, Norway
| | - Tor Tønnessen
- Department of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
| | - Simen Vatn
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Tone Bergene Aabrekk
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Vestfold Hospital Trust, Tønsberg, Norway
| | - Marte Lie Høivik
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
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Wetwittayakhlang P, Kotrri G, Bessissow T, Lakatos PL. How close are we to a success stratification tool for improving biological therapy in ulcerative colitis? Expert Opin Biol Ther 2024; 24:433-441. [PMID: 38903049 DOI: 10.1080/14712598.2024.2371049] [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: 04/01/2024] [Accepted: 06/18/2024] [Indexed: 06/22/2024]
Abstract
INTRODUCTION Biological therapies have become the standard treatment for ulcerative colitis (UC). However, clinical remission rates post-induction therapy remain modest at 40-50%, with many initial responders losing response over time. Current treatment strategies frequently rely on a 'trial and error' approach, leading to prolonged periods of ineffective and costly therapies for patients, accompanied by associated treatment complications. AREA COVERED This review discusses current evidence on risk stratification tools for predicting therapeutic efficacy and minimizing adverse events in UC management. Recent studies have identified predictive factors for biologic therapy response. In the context of personalized medicine, the goal is to identify patients at high risk of progression and complications, as well as those likely to respond to specific therapies. Essential risk stratification tools include clinical decision-making aids, biomarkers, genomics, multi-omics factors, endoscopic, imaging, and histological assessments. EXPERT OPINION Employing risk stratification tools to predict therapeutic response and prevent treatment-related complications is essential for precision medicine in the biological management of UC. These tools are necessary to select the most suitable treatment for each individual patient, thereby enhancing efficacy and safety.
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Affiliation(s)
- Panu Wetwittayakhlang
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC, Canada
| | - Gynter Kotrri
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC, Canada
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC, Canada
| | - Peter L Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC, Canada
- Department of Oncology and Medicine, Semmelweis University, Budapest, Hungary
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Behnoush AH, Maroufi SP, Reshadmanesh T, Mohtasham Kia Y, Norouzi M, Mohammadi SM, Klisic A, Khalaji A. Circulatory resistin levels in inflammatory bowel disease: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:107. [PMID: 38486190 PMCID: PMC10941394 DOI: 10.1186/s12876-024-03199-7] [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: 11/14/2023] [Accepted: 03/11/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing-remitting systemic disease of the gastrointestinal tract with rising incidence. Studies have shown that adipocytes play a crucial role in patients with IBD by actively participating in systemic immune responses. The present study was designed to investigate the correlation between the circulatory levels of resistin, as an adipokine, and active and remission phases of IBD in comparison with healthy controls. METHODS Relevant articles were retrieved from PubMed, Embase, the Web of Science, and Scopus from inception until June 2023. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of plasma/serum resistin levels between IBD patients, patients in remission, and healthy controls were conducted through random-effect meta-analysis. RESULTS A total of 19 studies were included, assessing 1836 cases. Meta-analysis indicated that generally, serum/plasma resistin levels were higher in IBD patients in comparison with healthy controls (SMD 1.33, 95% CI 0.58 to 2.08, p-value < 0.01). This was true for each of the UC and CD separate analyses, as well. Moreover, it was shown that higher serum/plasma resistin levels were detected in the active phase of IBD than in the remission phase (SMD 1.04, 95% CI 0.65 to 1.42, p-value = 0.01). Finally, higher serum/plasma resistin levels were found in the remission phase compared to healthy controls (SMD 0.60, 95% CI 0.15 to 1.06, p-value < 0.01). CONCLUSION The results of this systematic review and meta-analysis support the conclusion that circulating resistin levels are increased in IBD (both UC and CD). Also, higher resistin levels were recorded in the remission phase of IBD in comparison with healthy controls. This indicates that further studies may provide valuable insights into the role of resistin in the pathogenesis of IBD.
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Affiliation(s)
- Amir Hossein Behnoush
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, 1417613151, Tehran, Iran.
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Seyede Parmis Maroufi
- Neurosurgical Research Network, Universal Scientific Education and Research Network, Tehran University of Medical Sciences, Tehran, Iran
| | - Tara Reshadmanesh
- Student Research Center, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
| | | | - Mitra Norouzi
- Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | | | - Aleksandra Klisic
- Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
- Center for Laboratory Diagnostics, Primary Health Care Center, Podgorica, Montenegro
| | - Amirmohammad Khalaji
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, 1417613151, Tehran, Iran
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Pantalos G, Vaou N, Papachristidou S, Stavropoulou E, Tsigalou C, Voidarou C, Bezirtzoglou E. Antioxidant and Anti-Inflammatory Phytochemicals for the Treatment of Inflammatory Bowel Disease: A Systematic Review. APPLIED SCIENCES 2024; 14:2177. [DOI: 10.3390/app14052177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Inflammatory bowel disease (IBD) remains a burden for patients with increasing prevalence in industrialized countries. Phytochemicals are non-nutrient plant derived bioactive substances with antioxidant and anti-inflammatory effects that may prove beneficial to IBD patients. This review aims to overview current evidence on the application and impact of isolated phytochemicals or phytochemicals contained in plant extracts and essential oils on patients suffering from IBD. A systematic literature search was conducted for studies relating to the use of phytochemicals for the treatment of IBD. Ultimately, 37 human clinical trials and 3 systematic reviews providing human IBD patient data relevant to phytochemicals as therapeutic agents were included. Phytochemicals in the form of curcumin, Plantago ovata seeds, polyphenon E, silymarin, resveratrol supplements or an herbal preparation of myrrh, chamomile and coffee charcoal have evidence from human clinical trials supporting their safety and beneficial effects. Cannabinoids improve quality of life but not IBD outcomes. The addition of probiotics like B. longum to fructo-oligosaccharides promote healthy composition of the gut microbiome. Phytochemicals like mastiha, anthocyanins, berberine, tormentil, T2, ecabet sodium and Pycnogenol need more well-designed trials. Systematic research on phytochemicals can lead to the discovery of useful therapeutics. These secondary metabolites can be incorporated in current IBD treatment strategies to limit side effects, promote mucosal healing and provide higher quality of life to patients.
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Affiliation(s)
- George Pantalos
- Pediatric Surgery Department, Penteli General Children’s Hospital, 15236 Athens, Greece
| | - Natalia Vaou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece
| | - Smaragda Papachristidou
- Second Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, P.&A. Kyriakou Children’s Hospital, 11527 Athens, Greece
| | - Elisavet Stavropoulou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece
| | - Christina Tsigalou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece
| | - Chrysa Voidarou
- Department of Agriculture, School of Agriculture, University of Ioannina, 47100 Arta, Greece
| | - Eugenia Bezirtzoglou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece
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Hope E, Kuronen-Stewart C, Wilson DC, Henderson P, Clark C. The Impact of Biologic Therapies on Rate of Colectomy in Paediatric-onset Ulcerative Colitis - A Population-Based Cohort Study. J Pediatr Surg 2024; 59:230-234. [PMID: 37981545 DOI: 10.1016/j.jpedsurg.2023.10.034] [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: 10/07/2023] [Accepted: 10/11/2023] [Indexed: 11/21/2023]
Abstract
AIM Biologic therapies have been associated with reduced rate of colectomy in ulcerative colitis (UC) in adults, but data are limited in paediatric-onset UC. Our aim was to define the rate of colectomy in paediatric-onset UC, including post-transition into adult care, and to evaluate the impact of biologic therapies on rate of colectomy. METHOD All prevalent patients diagnosed with paediatric-onset UC in South-East Scotland were identified from a prospectively accrued database at our regional tertiary centre. Patients exposed to biologics or surgery were identified and further data collected from health records. Kaplan-Meier analysis was used to calculate cumulative risk of colectomy over time. RESULTS 145 prevalent patients were identified between 2000 and 2021. Median follow-up was 7.9 years (IQR 4.1-13.1). 23 patients (16 %) underwent a colectomy. 50/145 (34 %) patients received biologic therapy, and 13/23 (57 %) patients who underwent colectomy received biologics. The cumulative risk of colectomy across the whole cohort at 1, 5, and 10 years was 3 %, 13 % and 16 %, respectively. Patients exposed to biologics had a higher colectomy rate at 5 and 10 years (22 % and 34 %). Patients in the pre-biologic era (2000-2008) had non-significantly reduced time from diagnosis to colectomy (2.4 vs 3.7 years, p = 0.204). CONCLUSION We have defined the 1-, 5-, and 10-year colectomy rate in a population-based cohort of Paediatric-onset UC patients. Patients who received biologic therapy had a significantly increased risk of colectomy. Increased severity of disease in these patients may account for the greater colectomy risk. LEVEL OF EVIDENCE Level 1.
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Affiliation(s)
- Emma Hope
- Department of Paediatric Surgery, Royal Hospital for Children and Young People, Edinburgh, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Cameron Kuronen-Stewart
- Department of Paediatric Surgery, Royal Hospital for Children and Young People, Edinburgh, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK.
| | - David C Wilson
- Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK; Department of Child Life and Health, University of Edinburgh, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Paul Henderson
- Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK; Department of Child Life and Health, University of Edinburgh, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Claire Clark
- Department of Paediatric Surgery, Royal Hospital for Children and Young People, Edinburgh, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK
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10
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Lenfant M, Verstockt B, Sabino J, Vermeire S, Ferrante M. The assessment of segmental healing by the Modified Mayo Endoscopic Score (MMES) complements the prediction of long-term clinical outcomes in patients with ulcerative colitis. Aliment Pharmacol Ther 2024; 59:64-70. [PMID: 37843544 DOI: 10.1111/apt.17753] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/10/2023] [Accepted: 09/25/2023] [Indexed: 10/17/2023]
Abstract
BACKGROUND AND AIMS Current endoscopic scoring systems for ulcerative colitis (UC) do not consider the extent of mucosal inflammation. The modified Mayo endoscopic score (MMES) was developed to detect segmental endoscopic improvement. We evaluated the ability of the MMES to predict long-term clinical outcomes and compared it to the widely used Mayo endoscopic subscore (MES). METHODS Consecutive patients with moderate to severe UC starting biological therapy were enrolled between January 2014 and September 2017 in this prospective observational study. A clinical and endoscopic evaluation was performed at baseline and at week 8/14. A modified Mayo score was used to grade clinical activity, MES and MMES were used to evaluate endoscopic activity. Patients were divided into 3 groups according to the evolution of endoscopic activity, namely endoscopic improvement (MES ≤ 1), segmental endoscopic response only (MES > 1, but decrease in MMES ≥ 30%) or no endoscopic response (all others). Over the follow-up period clinical relapse-, discontinuation- and colectomy-free survival were assessed. RESULTS A total of 150 patients were included (48% female, median age 42 years, median disease duration 7 years) with a median follow-up of 61 months. We identified 69 patients with endoscopic improvement, 27 with segmental endoscopic response and 54 without endoscopic response. Patients with segmental endoscopic response showed intermediate long-term clinical outcomes as compared to the other two groups (log rank p = 0.003 for clinical relapse-, and p < 0.001 for both discontinuation- and colectomy-free survival). CONCLUSIONS The MMES exhibited a benefit in predicting long-term outcome in UC even though endoscopic improvement remains the strongest predictor.
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Affiliation(s)
- Matthias Lenfant
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - João Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
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11
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Sokic-Milutinovic A, Milosavljevic T. Inflammatory Bowel Disease: From Conventional Immunosuppression to Biologic Therapy. Dig Dis 2023; 42:325-335. [PMID: 38096793 DOI: 10.1159/000535647] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 12/04/2023] [Indexed: 07/17/2024]
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) are chronic, recurrent inflammatory diseases with partly understood etiology and pathogenesis. The course of IBD, both ulcerative colitis and Crohn's disease, is characterized by periods of relapse and remission with the possible occurrence of extraintestinal manifestations. SUMMARY During the last decades, therapeutic goals in IBD evolved toward endoscopic remission and mucosal healing creating the need for early administration of disease-modifying agents (DMAs). DMAs include conventional immunosuppressants (thiopurines, methotrexate), biologic drugs (anti-TNF, anti-integrin, and anti-IL-12/23 monoclonal antibodies), and small molecules (JAK inhibitors, S1P receptor modulators). Patients with aggressive course of disease and risk factors for poor prognosis should be treated with biologic therapy early, while conventional immunomodulators should be used in those with milder course of disease in the absence of risk factors. KEY MESSAGES Challenges in the treatment of IBD patients include the choice of effective yet safe drug and prevention or overcoming loss of response.
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Affiliation(s)
- Aleksandra Sokic-Milutinovic
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
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12
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Giddings HL, Ng KS, Solomon MJ, Steffens D, Van Buskirk J, Young J. Reducing rate of total colectomies for ulcerative colitis but higher morbidity in the biologic era: an 18-year linked data study from New South Wales Australia. ANZ J Surg 2023; 93:2928-2938. [PMID: 37795917 DOI: 10.1111/ans.18713] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 09/06/2023] [Accepted: 09/19/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND This study aims to investigate the trends in UC surgery in New South Wales (NSW) at a population level. METHODS A retrospective data linkage study of the NSW population was performed. Patients of any age with a diagnosis of UC who underwent a total abdominal colectomy (TAC) ± proctectomy between Jul-2001 and Jun-2019 were included. The age adjusted population rate was calculated using Australian Bureau of Statistics data. Multivariable linear regression modelled the trend of TAC rates, and assessed the effect of infliximab (listed on the Pharmaceutical Benefits Scheme for UC in Apr-2014). RESULTS A total of 1365 patients underwent a TAC ± proctectomy (mean age 47.0 years (±18.6), 59% Male). Controlling for differences between age groups, the annual rate of UC TACs decreased by 2.4% each year (95% CI 1.4%-3.4%) over the 18-year period from 1.30/100000 (2002) to 0.84/100000 (2019). An additional incremental decrease in the rate of TACs was observed after 2014 (OR 0.83, 95% CI 0.69-1.00). There was no change in the proportion of TACs performed emergently over the study period (OR 1.02, 95% CI 0.998-1.04). The odds of experiencing any perioperative surgical complication (aOR 1.54, 95% CI 1.01-2.33, P = 0.043), and requiring ICU admission (aOR 1.85, 95% CI 1.24-2.76, P = 0.003) significantly increased in 2014-2019 compared to 2002-2007. CONCLUSIONS The rate of TACs for UC has declined over the past two decades. This rate decrease may have been further influenced by the introduction of biologics. Higher rates of complications and ICU admissions in the biologic era may indicate poorer patient physiological status at the time of surgery.
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Affiliation(s)
- Hugh L Giddings
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Kheng-Seong Ng
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Michael J Solomon
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Daniel Steffens
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Joe Van Buskirk
- Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Public Health Research Analytics and Methods for Evidence, Sydney Local Health District, Sydney, New South Wales, Australia
| | - Jane Young
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
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13
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Tong JKC, Mascuilli T, Wirtalla C, Aarons CB, Saur NM, Mahmoud NN, Karakousis GC, Kelz RR. Evaluating Changes in Surgical Outcomes for Patients With Inflammatory Bowel Disease Following Medicaid Expansion. Inflamm Bowel Dis 2023; 29:1579-1585. [PMID: 36573827 DOI: 10.1093/ibd/izac255] [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: 02/02/2022] [Indexed: 10/05/2023]
Abstract
BACKGROUND Little is known about the impact of Medicaid expansion on the surgical care of inflammatory bowel disease. We sought to determine whether Medicaid expansion is associated with improved postsurgical outcomes for patients with inflammatory bowel disease undergoing a colorectal resection. METHODS We performed a risk-adjusted difference-in-difference study examining postsurgical outcomes for patients ages 26 to 64 with Crohn's disease or ulcerative colitis undergoing a colorectal resection across 15 states that did and did not expand Medicaid before (2012-2013) and after (2016-2018) policy reform. Primary study outcomes included 30-day readmission and postoperative complication. RESULTS Study population included 11 394 patients with inflammatory bowel disease that underwent a colorectal resection. States that underwent Medicaid expansion were associated with a rise in Medicaid enrollment following policy reform (11.8% pre-Medicaid expansion vs 19.7% post-Medicaid expansion). Difference-in-difference analysis revealed a statistically significant lower odds of 30-day readmission in patients undergoing a colorectal resection in expansion states following policy reform relative to patients in nonexpansion states prior to reform (odds ratio, 0.56; 95% confidence interval, 0.36-0.86). No changes in odds of postoperative complication were noted across expansion and nonexpansion states. CONCLUSIONS Medicaid expansion is associated with a rise in Medicaid enrollment in expansion states following policy reform. There were greater improvements in postoperative outcomes associated with patients in expansion states following policy reform relative to patients in nonexpansion states prior to reform, which may have been related to improved perioperative care and medical management.
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Affiliation(s)
- Jason K C Tong
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
- National Clinicians Scholars Veterans Affairs Scholar, Philadelphia, PA, USA
| | - Tory Mascuilli
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
| | - Christopher Wirtalla
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
| | - Cary B Aarons
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
- University of Pennsylvania, Department of Surgery, Division of Colon and Rectal Surgery, Philadelphia, PA, USA
| | - Nicole M Saur
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
- University of Pennsylvania, Department of Surgery, Division of Colon and Rectal Surgery, Philadelphia, PA, USA
| | - Najjia N Mahmoud
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
- University of Pennsylvania, Department of Surgery, Division of Colon and Rectal Surgery, Philadelphia, PA, USA
| | - Giorgos C Karakousis
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Rachel R Kelz
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
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14
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Morrison HA, Trusiano B, Rowe AJ, Allen IC. Negative regulatory NLRs mitigate inflammation via NF-κB pathway signaling in inflammatory bowel disease. Biomed J 2023; 46:100616. [PMID: 37321320 PMCID: PMC10494316 DOI: 10.1016/j.bj.2023.100616] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 06/06/2023] [Accepted: 06/10/2023] [Indexed: 06/17/2023] Open
Abstract
A subset of Nucleotide-binding and leucine-rich repeat-containing receptors (NLRs) function to mitigate overzealous pro-inflammatory signaling produced by NF-κB activation. Under normal pathophysiologic conditions, proper signaling by these NLRs protect against potential autoimmune responses. These NLRs associate with several different proteins within both the canonical and noncanonical NF-κB signaling pathways to either prevent activation of the pathway or inhibit signal transduction. Inhibition of the NF-κB pathways ultimately dampens the production of pro-inflammatory cytokines and activation of other downstream pro-inflammatory signaling mechanisms. Dysregulation of these NLRs, including NLRC3, NLRX1, and NLRP12, have been reported in human inflammatory bowel disease (IBD) and colorectal cancer patients, suggesting the potential of these NLRs as biomarkers for disease detection. Mouse models deficient in these NLRs also have increased susceptibility to colitis and colitis-associated colorectal cancer. While current standard of care for IBD patients and FDA-approved therapeutics function to remedy symptoms associated with IBD and chronic inflammation, these negative regulatory NLRs have yet to be explored as potential drug targets. In this review, we describe a comprehensive overview of recent studies that have evaluated the role of NLRC3, NLRX1, and NLRP12 in IBD and colitis-associated colorectal cancer.
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Affiliation(s)
- Holly A Morrison
- Virginia Tech, Virginia Maryland College of Veterinary Medicine, Department of Biomedical Science and Pathobiology, Blacksburg VA, USA
| | - Brie Trusiano
- Virginia Tech, Virginia Maryland College of Veterinary Medicine, Department of Biomedical Science and Pathobiology, Blacksburg VA, USA
| | - Audrey J Rowe
- Virginia Tech, Virginia Maryland College of Veterinary Medicine, Department of Biomedical Science and Pathobiology, Blacksburg VA, USA
| | - Irving C Allen
- Virginia Tech, Virginia Maryland College of Veterinary Medicine, Department of Biomedical Science and Pathobiology, Blacksburg VA, USA; Virginia Tech, Department of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke VA, USA; Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, USA.
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15
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Murthy SK, Kuenzig ME, Windsor JW, Matthews P, Tandon P, Benchimol EI, Bernstein CN, Bitton A, Coward S, Jones JL, Kaplan GG, Lee K, Targownik LE, Peña-Sánchez JN, Rohatinsky N, Ghandeharian S, Meka S, Chis RS, Gupta S, Cheah E, Davis T, Weinstein J, Im JHB, Goddard Q, Gorospe J, Loschiavo J, McQuaid K, D’Addario J, Silver K, Oppenheim R, Singh H. The 2023 Impact of Inflammatory Bowel Disease in Canada: Cancer and IBD. J Can Assoc Gastroenterol 2023; 6:S83-S96. [PMID: 37674502 PMCID: PMC10478814 DOI: 10.1093/jcag/gwad006] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/08/2023] Open
Abstract
Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden. However, the cumulative risk of cancer, even among those with IBD is still low. Some studies suggest that IBD-CRC incidence has declined over the years, possibly owing to improved treatment standards and improved detection and management of early neoplastic lesions. Across studies of extra-intestinal cancers, there are generally higher incidences of melanoma, hepatobiliary cancer, and lung cancer and no higher incidences of breast cancer or prostate cancer, with equivocal risk of cervical cancer, among persons with IBD. While the relative risks of some extra-intestinal cancers are increased with treatment, the absolute risks of these cancers remain low and the decision to forego treatment in light of these risks should be carefully weighed against the increased risks of intestinal cancers and other disease-related complications with undertreated inflammatory disease. Quality improvement efforts should focus on optimized surveillance of cancers for which surveillance strategies exist (colorectal cancer, hepatobiliary cancer, cervical cancers, and skin cancers) and the development of cost-effective surveillance strategies for less common cancers associated with IBD.
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Affiliation(s)
- Sanjay K Murthy
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada
| | - M Ellen Kuenzig
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Joseph W Windsor
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | | | - Parul Tandon
- Department of Gastroenterology and Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Eric I Benchimol
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
- Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Charles N Bernstein
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Alain Bitton
- Division of Gastroenterology and Hepatology, McGill University Health Centre IBD Centre, McGill University, Montréal, Quebec, Canada
| | - Stephanie Coward
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Jennifer L Jones
- Departments of Medicine, Clinical Health, and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Gilaad G Kaplan
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Kate Lee
- Crohn’s and Colitis Canada, Toronto, Ontario, Canada
| | - Laura E Targownik
- Division of Gastroenterology and Hepatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Juan-Nicolás Peña-Sánchez
- Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Noelle Rohatinsky
- College of Nursing, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | | | - Saketh Meka
- Department of Neuroscience, McGill University, Montreal, Quebec, Canada
| | - Roxana S Chis
- Department of Gastroenterology and Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sarang Gupta
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Eric Cheah
- Department of Gastroenterology and Clinical Nutrition, The Royal Children’s Hospital Melbourne, Parkville, Australia
| | - Tal Davis
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Jake Weinstein
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - James H B Im
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Quinn Goddard
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Julia Gorospe
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | | | | | | | - Ken Silver
- Crohn’s and Colitis Canada, Toronto, Ontario, Canada
| | | | - Harminder Singh
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- CancerCare Manitoba Research Institute, Winnipeg, Manitoba, Canada
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16
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Park SH. Golimumab for Ulcerative Colitis: One More Option to SAVE the Colon. CROHN'S & COLITIS 360 2023; 5:otad046. [PMID: 37691730 PMCID: PMC10492443 DOI: 10.1093/crocol/otad046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/12/2023] Open
Affiliation(s)
- Sang Hyoung Park
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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17
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Sarangi SC, Pattnaik SS, Sinha S, R G. An update on efficacy and safety comparison of biologics in treatment of inflammatory bowel disease targeting TNF-α, interleukins, leukocyte trafficking, Janus-kinase, and sphingosine-1-phosphate receptor. Expert Rev Gastroenterol Hepatol 2023; 17:837-861. [PMID: 36469630 DOI: 10.1080/17474124.2022.2155136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 11/30/2022] [Indexed: 12/08/2022]
Abstract
INTRODUCTION Along with the rising prevalence of inflammatory bowel disease (IBD) [Crohn's disease (CD) and ulcerative colitis (UC)], biological therapies need an update/insight. AREA COVERED This review included randomized controlled trials (RCTs) from PubMed database (2000-October 2022) of approved biologics and small molecules with primary outcome analysis on efficacy (clinical response/remission/mucosal healing) and/or adverse events (AEs). Considered for this review under biologics classes are TNF-α inhibitors, leukocyte trafficking inhibitors, and anti IL-12/IL-23; and under small molecules are Janus-kinase inhibitors, and sphingosine-1-phosphate receptor modulators. EXPERT OPINION In CD, clinical response and remission were better with tofacitinib (61.23%) and infliximab (44.86%), respectively, in the induction phase, and these were better with ustekinumab in the maintenance phase. In UC, the maximum rate of response, remission, and mucosal healing were obtained with infliximab during the induction phase (67.49%, 35.99%, and 60.25%, respectively). During the maintenance phase, response rate was better with ustekinumab, but remission and mucosal healing were better with vedolizumab. The combined percentage of AEs was highest with infliximab (174.45%) and least with ozanimod (23.04%), and most commonly belonged to the 'infection and infestation system organ class (SOC).' These efficacy and safety analyses will help in the optimization of biologic treatment in IBD.
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Affiliation(s)
| | - Soumya S Pattnaik
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
| | - Surabhi Sinha
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
| | - Govindaraj R
- Department of Radiodiagnosis, NEIGRIHMS, Shilong, India
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18
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Kim ES, Kim SK, Park DI, Kim HJ, Lee YJ, Koo JS, Kim ES, Yoon H, Lee JH, Kim JW, Shin SJ, Kim HW, Kim HS, Park YS, Kim YS, Kim TO, Lee J, Choi CH, Han DS, Chun J, Kim HS. Comparison of the Pharmacokinetics of CT-P13 Between Crohn's Disease and Ulcerative Colitis. J Clin Gastroenterol 2023; 57:601-609. [PMID: 35470308 DOI: 10.1097/mcg.0000000000001715] [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: 09/25/2021] [Accepted: 03/20/2022] [Indexed: 12/10/2022]
Abstract
BACKGROUND We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (μg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.
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Affiliation(s)
- Eun Soo Kim
- Department of Internal Medicine, Kyungpook National University, School of Medicine
| | - Sung Kook Kim
- Department of Internal Medicine, Kyungpook National University, School of Medicine
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - Hyo Jong Kim
- Center for Crohn's and Colitis, Kyung Hee University Hospital
| | - Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu
| | - Ja Seol Koo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ansan Hospital, Korea University College of Medicine, Ansan
| | - Eun Sun Kim
- Department of Internal Medicine, Korea University College of Medicine
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Ji Hyun Lee
- Digestive Endoscopic Center, Seoul Song Do Colorectal Hospital
| | - Ji Won Kim
- Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine
| | - Sung Jae Shin
- Department of Internal Medicine, Ajou University School of Medicine, Suwon
| | - Hyung Wook Kim
- Department of Internal Medicine, Pusan National University School of Medicine And Medical Research Institute
| | - Hyun-Soo Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju
| | - Young Sook Park
- Department of Internal Medicine, Eulji University School of Medicine, Eulji Hospital
| | - You Sun Kim
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine
| | - Tae Oh Kim
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan
| | - Jun Lee
- Department of Internal Medicine, Chosun University, School of Medicine
| | - Chang Hwan Choi
- Department of Internal Medicine, College of Medicine, Chung-Ang University
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea
| | - Jaeyoung Chun
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul
| | - Hyun Soo Kim
- Department of Internal Medicine, Chonnam University Medical School, Gwangju
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Gordon BL, Battat R. Therapeutic Drug Monitoring of Infliximab in Acute Severe Ulcerative Colitis. J Clin Med 2023; 12:jcm12103378. [PMID: 37240484 DOI: 10.3390/jcm12103378] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/01/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
Therapeutic drug monitoring (TDM) is a useful strategy in ulcerative colitis (UC). Nearly a quarter of UC patients will experience acute severe UC (ASUC) in their lifetime, including 30% who will fail first-line corticosteroid therapy. Steroid-refractory ASUC patients require salvage therapy with infliximab, cyclosporine, or colectomy. Fewer data are available for the use of TDM of infliximab in ASUC. The pharmacokinetics of ASUC make TDM in this population more complex. High inflammatory burden is associated with increased infliximab clearance, which is associated with lower infliximab drug concentrations. Observational data support the association between increased serum infliximab concentrations, lower clearance, and favorable clinical and endoscopic outcomes, as well as decreased rates of colectomy. Data regarding the benefit of accelerated or intensified dosing strategies of infliximab-as well as target drug concentration thresholds-in ASUC patients remain more equivocal, though limited by their observational nature. Studies are underway to further evaluate optimal dosing and TDM targets in this population. This review examines the evidence for TDM in patients with ASUC, with a focus on infliximab.
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Affiliation(s)
- Benjamin L Gordon
- Division of Gastroenterology and Hepatology, New York-Presbyterian/Weill Cornell Medical Center, New York, NY 10065, USA
| | - Robert Battat
- Center for Clinical and Translational Research in Inflammatory Bowel Diseases, Centre Hospitalier de l'Université de Montréal, Montreal, QC H2X 0A9, Canada
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20
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Shin SH, Oh K, Hong SN, Lee J, Oh SJ, Kim ES, Na SY, Kang SB, Koh SJ, Bang KB, Jung SA, Jung SH, Kim KO, Park SH, Yang SK, Choi CH, Ye BD. Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: a KASID multicenter cohort study. Therap Adv Gastroenterol 2023; 16:17562848231154103. [PMID: 36950251 PMCID: PMC10026122 DOI: 10.1177/17562848231154103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 01/13/2023] [Indexed: 03/24/2023] Open
Abstract
Background Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with ulcerative colitis (UC). However, the real-life data on tofacitinib in Asian UC patients are limited. Objective To investigate the real-life effectiveness and safety of tofacitinib induction and maintenance treatment in Korean patients with UC. Design This was a retrospective study on patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Methods Clinical remission at week 52, defined as a partial Mayo score of ⩽2 with a combined rectal bleeding subscore and stool frequency subscore of ⩽1, was used as the primary outcome. Adverse events (AEs), including herpes zoster and deep vein thrombosis, were also evaluated. Results A total of 148 patients with UC were started on tofacitinib. Clinical remission rates of 60.6%, 54.9%, and 52.8% were reported at weeks 16, 24, and 52, respectively. Clinical response rates of 71.8%, 67.6%, and 59.9% were reported at weeks 16, 24, and 52, respectively. Endoscopic remission rates at weeks 16 and 52 were 52.4% and 30.8% based on the Mayo endoscopic subscore and 20.7% and 15.2% based on the UC endoscopic index of severity (UCEIS), respectively. A higher UCEIS at baseline was negatively associated with clinical response [adjusted odds ratio (aOR): 0.774, p = 0.029] and corticosteroid-free clinical response (aOR: 0.782, p = 0.035) at week 52. AEs occurred in 19 patients (12.8%) and serious AEs in 12 patients (8.1%). Herpes zoster occurred in four patients (2.7%). One patient (0.7%) suffered from deep vein thrombosis. Conclusions Tofacitinib was an effective induction and maintenance treatment with an acceptable safety profile in Korean patients with UC. Plain language summary Real-life effectiveness and safety of tofacitinib treatment in Korean patients with ulcerative colitis Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa that usually presents with bloody diarrhea and abdominal pain. Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with UC. However, real-life data on the effectiveness of tofacitinib in Asian patients with UC are limited. To investigate the real-life effectiveness and safety of tofacitinib treatment in Korean patients with UC, we retrospectively analyzed the data of 148 patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission (i.e. complete improvement of symptoms) was achieved in 60.6% and 52.8% of patients at weeks 16 and 52, respectively. Endoscopic remission was achieved in 52.4% and 30.8% of patients at weeks 16 and 52, respectively. A higher baseline score of the UC endoscopic index of severity, which is one of the endoscopic indices that evaluate the severity of inflammation of the colon, was negatively associated with clinical response (i.e. partial improvement of symptoms). Adverse events (AEs) including herpes zoster and deep vein thrombosis occurred in 19 patients (12.8%) and serious AEs occurred in 12 patients (8.1%). Our real-life study shows that tofacitinib is a clinically effective treatment for Korean patients with UC, and the incidence of AEs was also similar to those observed in other real-world studies.
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Affiliation(s)
- Seung Hwan Shin
- Department of Gastroenterology, University of
Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kyunghwan Oh
- Department of Gastroenterology, University of
Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sung Noh Hong
- Division of Gastroenterology, Department of
Medicine, Samsung Medical Center, Sungkyunkwan University School of
Medicine, Seoul, Korea
| | - Jungbok Lee
- Department of Biostatistics and Clinical
Epidemiology, Asan Medical Center, Seoul, Korea
| | - Shin Ju Oh
- Department of Gastroenterology, Kyung Hee
University College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology,
Department of Internal Medicine, School of Medicine, Kyungpook National
University, Daegu, Korea
| | - Soo-Young Na
- Department of Internal Medicine, Incheon St.
Mary’s Hospital, College of Medicine, The Catholic University of Korea,
Incheon, Korea
| | - Sang-Bum Kang
- Department of Internal Medicine, College of
Medicine, Daejeon St. Mary’s Hospital, The Catholic University of Korea,
Daejeon, Korea
| | - Seong-Joon Koh
- Department of Internal Medicine and Liver
Research Institute, Seoul National University College of Medicine, Seoul,
Korea
| | - Ki Bae Bang
- Department of Internal Medicine, Dankook
University College of Medicine, Cheonan, Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, Ewha Womans
University College of Medicine, Seoul, Korea
| | - Sung Hoon Jung
- Department of Internal Medicine, Eunpyeong St.
Mary’s Hospital, College of Medicine, The Catholic University of Korea,
Seoul, Korea
| | - Kyeong Ok Kim
- Division of Gastroenterology and Hepatology,
Department of Internal Medicine, Yeungnam University College of Medicine,
Daegu, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology and
Inflammatory Bowel Disease Center, University of Ulsan College of Medicine,
Asan Medical Center, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology and
Inflammatory Bowel Disease Center, University of Ulsan College of Medicine,
Asan Medical Center, Seoul, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang
University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973,
Korea
| | - Byong Duk Ye
- Department of Gastroenterology and
Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan
College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South
Korea
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21
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Fuxman C, Sicilia B, Linares ME, García-López S, González Sueyro R, González-Lamac Y, Zabana Y, Hinojosa J, Barreiro-de Acosta M, Balderramo D, Balfour D, Bellicoso M, Daffra P, Morelli D, Orsi M, Rausch A, Ruffinengo O, Toro M, Sambuelli A, Novillo A, Gomollón F, De Paula JA. GADECCU 2022 Guideline for the treatment of Ulcerative Colitis. Adaptation and updating of the GETECCU 2020 Guideline. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46 Suppl 1:S1-S56. [PMID: 36731724 DOI: 10.1016/j.gastrohep.2023.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/04/2023] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory disease that compromises the colon, affecting the quality of life of individuals of any age. In practice, there is a wide spectrum of clinical situations. The advances made in the physio pathogenesis of UC have allowed the development of new, more effective and safer therapeutic agents. OBJECTIVES To update and expand the evaluation of the efficacy and safety of relevant treatments for remission induction and maintenance after a mild, moderate or severe flare of UC. RECIPIENTS Gastroenterologists, coloproctologists, general practitioners, family physicians and others health professionals, interested in the treatment of UC. METHODOLOGY GADECCU authorities obtained authorization from GETECCU to adapt and update the GETECCU 2020 Guide for the treatment of UC. Prepared with GRADE methodology. A team was formed that included authors, a panel of experts, a nurse and a patient, methodological experts, and external reviewers. GRADE methodology was used with the new information. RESULTS A 118-page document was prepared with the 44 GADECCU 2022 recommendations, for different clinical situations and therapeutic options, according to levels of evidence. A section was added with the new molecules that are about to be available. CONCLUSIONS This guideline has been made in order to facilitate decision-making regarding the treatment of UC, adapting and updating the guide prepared by GETECCU in the year 2020.
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Affiliation(s)
- Claudia Fuxman
- Servicio de Gastroenterología, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
| | - Beatriz Sicilia
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Burgos, Burgos, España
| | - María Eugenia Linares
- Servicio de Gastroenterología, Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Santiago García-López
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, España
| | - Ramiro González Sueyro
- Servicio de Gastroenterología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Yago González-Lamac
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Mútua Terrassa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España
| | - Joaquín Hinojosa
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital de Manise, Valencia, España
| | - Manuel Barreiro-de Acosta
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, España
| | - Domingo Balderramo
- Servicio de Gastroenterología, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Deborah Balfour
- Unidad de Enfermedades Inflamatorias, HIGEA Clínica de Gastroenterología, Mendoza, Argentina
| | - Maricel Bellicoso
- Área de Gastroenterología, Inmunología Buenos Aires, Buenos Aires, Argentina
| | - Pamela Daffra
- Servicio de Gastroenterología, Hospital Central de Mendoza, Mendoza, Argentina
| | - Daniela Morelli
- Departamento de Educación, Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
| | - Marina Orsi
- Servicio de Gastroenterología Pediátrica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Astrid Rausch
- Servicio de Gastroenterología, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
| | - Orlando Ruffinengo
- Servicio de Gastroenterología, Hospital Provincial del Centenario, Rosario, Argentina
| | - Martín Toro
- Unidad de Enfermedades Inflamatorias, HIGEA Clínica de Gastroenterología, Mendoza, Argentina
| | - Alicia Sambuelli
- Sección de Enfermedades Inflamatorias Intestinales, Hospital Bonorino Udaondo, Buenos Aires, Argentina
| | - Abel Novillo
- Servicio de Gastroenterología, Sanatorio 9 de Julio, Tucumán, Argentina.
| | - Fernando Gomollón
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Instituto de Investigaciones Sanitarias de Aragón, Hospital Clínico Universitario Lozano Blesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestiva (CIBEREHD), Zaragoza, España
| | - Juan Andrés De Paula
- Servicio de Gastroenterología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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22
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Pakdin M, Zarei L, Bagheri Lankarani K, Ghahramani S. The cost of illness analysis of inflammatory bowel disease. BMC Gastroenterol 2023; 23:21. [PMID: 36658489 PMCID: PMC9854042 DOI: 10.1186/s12876-023-02648-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 01/10/2023] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic inflammatory condition involving individuals across all age groups. Recent data suggests the increase in the prevalence of IBD and the surge in applying the biologic drugs in which both change the cost of IBD in recent years. Comprehensive assessment of direct and indirect cost profiles associated with IBD in our area is scarce. This study aimed to determine the economic burden of IBD in Iran from a societal perspective, using cost diaries. METHODS Patients available on clinic registry and hospital information system (HIS), who were diagnosed with IBD, were invited to take part in this study. Demographic and clinical data, the healthcare resource utilization or cost items, absenteeism for the patients and their caregivers were obtained. The cost of the used resources were derived from national tariffs. The data regarding premature mortality in IBD patients was extracted from HIS. Productivity loss was estimated based on the human capital method. Then, cost date were calculated as mean annual costs per patient. RESULTS The cost diaries were obtained from 240 subjects (Ulcerative colitis: n = 168, Crohn's disease, n = 72). The mean annual costs per patient were 1077 US$ (95% CI 900-1253), and 1608 (95% CI 1256, 1960) for the patients with ulcerative colitis and Crohn's disease, respectively. Of the total costs, 58% and 63% were in terms of the indirect costs for the patients with ulcerative colitis and Crohn's disease, respectively. The cost of illness for country was found to be 22,331,079 US$ and 15,183,678 US$ for patients with ulcerative colitis and Crohn's disease, respectively. Highest nationwide economic burden of IBD was found for patients older than 40 years were estimated to be 8,198,519 US$ and 7,120,891 US$, for ulcerative colitis and Crohn's disease, respectively. CONCLUSION The medication was found to be the greatest contributor of direct medical costs. Productivity loss in terms of long-term disability and premature mortality were major components of IBD's economic burden in Iran.
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Affiliation(s)
- Majid Pakdin
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Leila Zarei
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kamran Bagheri Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sulmaz Ghahramani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran.
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23
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Na SY, Choi CH, Song EM, Bang KB, Park SH, Kim ES, Park JJ, Keum B, Lee CK, Lee BI, Ryoo SB, Koh SJ, Choi M, Kim JS. Korean clinical practice guidelines on biologics and small molecules for moderate-to-severe ulcerative colitis. Intest Res 2023; 21:61-87. [PMID: 35645321 PMCID: PMC9911265 DOI: 10.5217/ir.2022.00007] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 03/07/2022] [Indexed: 02/09/2023] Open
Abstract
Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4β7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.
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Affiliation(s)
- Soo-Young Na
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea,Correspondence to Chang Hwan Choi, Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea. Tel: +82-2-6299-1418, Fax: +82-2-6299-2064, E-mail:
| | - Eun Mi Song
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Ki Bae Bang
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jae Jun Park
- Department of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Bora Keum
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Chang Kyun Lee
- Department of Gastroenterology, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Bo-In Lee
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung-Bum Ryoo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seong-Joon Koh
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Miyoung Choi
- National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Dai N, Haidar O, Askari A, Segal JP. Colectomy rates in ulcerative colitis: A systematic review and meta-analysis. Dig Liver Dis 2023; 55:13-20. [PMID: 36180365 DOI: 10.1016/j.dld.2022.08.039] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 08/24/2022] [Accepted: 08/26/2022] [Indexed: 01/15/2023]
Abstract
BACKGROUND Surgical management in Ulcerative Colitis (UC) is typically utilised in medically refractory cases and, therefore, it is a useful marker for efficacy of medical management. AIMS To understand the changing prevalence of colectomy in UC over time. METHODS A systematic review was conducted using MEDLINE (1946-2021), EMBASE and EMBASE classic (1947-2021) to identify studies with a population of n>500 that reported colectomy rates in UC patients >18 years old. The primary outcome was the prevalence of colectomy at 1-, 5- and 10-years post-diagnosis. Secondary outcomes included colectomy rates in the pre-biologics (defined as pre-2004) and post-biologics eras (defined as post-2004). RESULTS Thirty-one studies with 294,359 patients with UC were included for review and meta-analysis. The prevalence of colectomy at 1-, 5- and 10-years post-diagnosis were 3% (95% CI 2%-6%), 5% (95% CI 2%-9%), 10% (95% CI 6%-16%) respectively. The pooled relative risk for colectomy in the post-biologics era was 0.68 (95% CI 0.42 to 1.09, p=0.10) at 1-year and 0.71 (95% CI 0.56 to 0.91, p<0.01) at 5-years post-diagnosis. CONCLUSION The overall colectomy rate has decreased over the past three decades. Biologics may have played a role in reducing the risk of colectomy, however the relative risk reduction is likely to be modest.
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Affiliation(s)
- Nick Dai
- Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
| | - Omar Haidar
- School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Alan Askari
- Luton and Dunstable University Hospital, Luton, UK
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25
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Wang X, Li Q, Sun S, Liang X, Li H, Huang J, Zhao T, Hu J, Liu J, Hu Z, Duan Y, He J. Network meta-analysis and cost-effectiveness analysis of infliximab, cyclosporine and tacrolimus for ulcerative colitis. Medicine (Baltimore) 2022; 101:e31850. [PMID: 36595876 PMCID: PMC9794301 DOI: 10.1097/md.0000000000031850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 06/16/2022] [Accepted: 06/20/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Assess the efficiency and cost-effectiveness of infliximab, cyclosporine and tacrolimus for the treatment of ulcerative colitis (UC). METHODS A literature search identified studies that investigated infliximab, cyclosporine or tacrolimus compared with placebo in UC patients. Short-term, long-term remission rates and response rates were employed to assess efficacy. Odds ratios with 95% confidence intervals were analyzed. A Markov model was constructed to simulate the progression in a cohort of patients with UC, with an over 10 years of time horizon, with a discount rate of 3%, and established threshold of €30,000/quality-adjusted life-year (QALY) or ¥82442/QALY. RESULTS Results of network meta-analysis showed that the order was cyclosporine, tacrolimus, infliximab and placebo from high rate to low with regard to short-term clinical response. The comparison between infliximab versus cyclosporine achieved an incremental cost effectiveness ratio (ICER) of €184435/QALY and ¥531607/QALY, with a 0.34893 QALYs difference of efficacy, and an incremental cost of €64355 and ¥185494. Tacrolimus versus cyclosporine reached an ICER of €44236/QALY and ¥57494/QALY, with a difference of 0.40963 QALYs in efficacy, and a raising cost to €18120 and ¥23551. The probabilistic sensitivity analysis shows that cyclosporine would be cost-effective in the 75.8% of the simulations, tacrolimus in the 24.2%, and infliximab for the 0%. CONCLUSION Infliximab, cyclosporine and tacrolimus as salvage therapies are efficacious. For long-term of clinical remission, the order of pharmacological agents was tacrolimus, infliximab and cyclosporine from high efficacy to low while no significant difference is seen. In cost-effectiveness analysis, the cyclosporine versus infliximab or tacrolimus is expected to be at best.
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Affiliation(s)
- Xueqi Wang
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Qiubo Li
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Shijiang Sun
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Xi Liang
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Huijing Li
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Jing Huang
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Tianhe Zhao
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Jingnan Hu
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Jianxin Liu
- College of Electronic Countermeasure, National University of Defense Technology, Hefei, Anhui, China
| | - Zhenbiao Hu
- College of Electronic Countermeasure, National University of Defense Technology, Hefei, Anhui, China
| | - Yangyang Duan
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Jianming He
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research (Hebei), Shijiazhuang, Hebei, China
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26
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Wetwittayakhlang P, Gonczi L, Lakatos L, Kurti Z, Golovics P, Pandur T, David G, Erdelyi Z, Szita I, Lakatos PL. Long-term Colectomy rates of Ulcerative Colitis over 40-year of Different Therapeutic eras - Results from Western Hungarian Population-based Inception Cohort between 1977-2020. J Crohns Colitis 2022; 17:712-721. [PMID: 36539328 DOI: 10.1093/ecco-jcc/jjac188] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Few population-based studies have investigated the long-term colectomy rates of ulcerative colitis (UC). We aimed to assess the colectomy rates over 40 years of different therapeutic eras in a prospective population-based inception cohort from Veszprem Province, Western Hungary. METHODS Patient inclusion lasted between January1,1977, and December31, 2018. Patient follow-up ended December 31,2020. Colectomy rates and disease course were examined in three different eras based on the time of UC diagnosis; cohort-A(1977-1995),cohort-B(1996-2008), and cohort C(2009-2018). RESULTS A total of 1,370 incident UC patients were included (male 51.2%,median age at diagnosis:37 years). Median follow-up was 17 years (IQR 9-24); 87 patients(6.4%) underwent colectomy. The cumulative probability of colectomy in the total population was 2.6%(95%CI 2.2-3.0), 4.2%(95%CI 3.6-4.8), 7.0%(95%CI 6.2-7.8), and 10.4%(95%CI 9.1-11.7) after 5, 10, 20, and 30 years, respectively. The proportion of extensive colitis at diagnosis increased over time (24.2%/24.3%/34.9% in cohorts A/B/C,p=0.001). Overall exposure to immunomodulators (11.3%/20.9%/34.4% in cohorts A/B/C,p<0.001), as well as the probability for biological therapy initiation increased over time; 0%/ 3.3%(95%CI 2.6-4.0)/ 13.9%(95%CI 12.1-15.7), p<0.001. There were no statistically significant differences in the cumulative probability of colectomies between cohorts A/B/C; 1.7% (95%CI 1.0-2.4), 2.5%(95%CI 1.9-3.1), and 3.7%(95%CI 2.7-4.7) after 5 years; 3.5%(95%CI 2.5-4.5), 4.2%(95%CI 3.4-5.0), and 4.5%(95%CI 3.3-5.7) after 10 years; and 7.5% (95%CI 6.1-8.9) and 6.3% (95%CI 5.2-7.4) in cohorts A/B after 20 years (Log-rank=0.588). Extensive colitis (HR;2.24:95%CI 1.55-3.23) and continuous active disease activity (HR;6.36:95%CI 3.46-11.67) were independent predictors for colectomy. CONCLUSION No differences in colectomy rates have been observed in the incident UC patients over 40 years despite increasing use of immunomodulators and biological therapies.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada.,Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Lorant Gonczi
- Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Laszlo Lakatos
- Department of Gastroenterology, Ferenc Csolnoky Hospital, Veszprem, Hungary
| | - Zsuzsanna Kurti
- Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Petra Golovics
- Department of Gastroenterology, Hungarian Defence Forces Medical Centre, Budapest, Hungary
| | - Tunde Pandur
- Department of Gastroenterology, Grof Eszterhazy Hospital, Papa, Hungary
| | - Gyula David
- Department of Gastroenterology, Ferenc Csolnoky Hospital, Veszprem, Hungary
| | - Zsuzsanna Erdelyi
- Department of Gastroenterology, Ferenc Csolnoky Hospital, Veszprem, Hungary
| | - Istvan Szita
- Department of Gastroenterology, Ferenc Csolnoky Hospital, Veszprem, Hungary
| | - Peter L Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada.,Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
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Nasab AS, Finkler M, DeLozier S, Sferra TJ, Splawski J, Moses J. Comparison of Short-Term Outcomes for Standard Versus Nonstandard Induction Dosing of Infliximab for Pediatric Inflammatory Bowel Disease. J Pediatr Pharmacol Ther 2022; 27:732-738. [DOI: 10.5863/1551-6776-27.7.732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 01/10/2022] [Indexed: 11/18/2022]
Abstract
OBJECTIVE
Recent studies have emphasized the early use of infliximab (IFX) in pediatric patients with inflammatory bowel disease. Standard dosing of 5 mg/kg/dose may not be sufficient to achieve optimal clinical outcomes. The aim of our study was to compare short-term outcomes with standard dosing of IFX to higher, nonstandard dosing of IFX for induction therapy.
METHODS
Retrospective study of 162 pediatric patients receiving either standard (5–6 mg/kg, n = 90) or nonstandard (>6 mg/kg, n = 72) dosing of IFX during induction was performed. Patient demographics, clinical outcomes, and laboratory data were collected. Need for dose escalation during the first 6 months, combination therapy with immunomodulators, and steroid-free progression were investigated.
RESULTS
Clinical remission rates between the 2 groups were significantly different, with patients receiving nonstandard dosing demonstrating higher rates (58% vs 78%; p = 0.012). Use of combination therapy with immunomodulators was significantly different between standard and nonstandard groups (80% vs 48%; p < 0.001). Numeric trend in need for IFX dose escalation in the first 6 months was seen between standard and nonstandard groups (54% vs 39%, respectively; p = 0.087). Post-induction IFX trough concentrations, rates of antibody development, drug discontinuation, and infusion reaction were similar.
CONCLUSIONS
Nonstandard induction dosing of IFX was associated with higher rates of clinical remission, despite similar rates of serum IFX trough concentrations. There was a numeric trend towards the standard group requiring dose escalation within the first 6 months of therapy. Patients given nonstandard dosing may achieve superior clinical outcomes compared with those on standard dosing.
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Affiliation(s)
- Arian S. Nasab
- Department of Pediatrics (ASN), UH–Rainbow Babies and Children's Hospital Cleveland, OH
| | - Michael Finkler
- Division of Pediatric Gastroenterology (MF, TJS, JS, JM), UH–Rainbow Babies and Children's Hospital Cleveland, OH
| | - Sarah DeLozier
- Center for Clinical Research (SD), University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Thomas J. Sferra
- Division of Pediatric Gastroenterology (MF, TJS, JS, JM), UH–Rainbow Babies and Children's Hospital Cleveland, OH
| | - Judy Splawski
- Division of Pediatric Gastroenterology (MF, TJS, JS, JM), UH–Rainbow Babies and Children's Hospital Cleveland, OH
| | - Jonathan Moses
- Division of Pediatric Gastroenterology (MF, TJS, JS, JM), UH–Rainbow Babies and Children's Hospital Cleveland, OH
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Dose-Intensified Infliximab Rescue Therapy for Severe Ulcerative Colitis Does Not Reduce Short-term Colectomy Rates or Increase Postoperative Complications. Dis Colon Rectum 2022; 65:1232-1240. [PMID: 35714346 DOI: 10.1097/dcr.0000000000002176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Dose-intensified rescue therapy with infliximab for hospitalized patients with ulcerative colitis has become increasingly popular in recent years. However, there is ongoing debate about both the efficacy of these regimens to reduce the rate of colectomy and the associated risks of increased infliximab exposure. OBJECTIVE The purpose of this study was to compare the colectomy and postoperative complication rates in hospitalized patients with severe ulcerative colitis receiving standard infliximab induction therapy (3 doses of 5 mg/kg at weeks 0, 2, and 6) and dose-intensified regimens including a higher weight-based dosing or more rapid interval. DESIGN This was a retrospective cohort study. SETTINGS This study was conducted at an academic tertiary care hospital. PATIENTS A total of 145 adult patients received inpatient rescue infliximab therapy for the treatment of ulcerative colitis between 2008 and 2020. MAIN OUTCOME MEASURES The primary outcome was colectomy rate within 3 months of rescue therapy. Secondary outcomes include mid-term colectomy rates, as well as perioperative complications in patients receiving colectomy within 3 months of rescue infliximab initiation. RESULTS The proportion of dose-intensified regimens increased over time. Unadjusted 3-month colectomy rates were 14% in patients who received standard rescue infliximab dosing, 16% in patients given a single dose-escalated dose, and 24% in patients given multiple inpatient dose-escalated doses. These rates were not statistically significantly different. Of the patients requiring colectomy within 3 months of infliximab rescue, those who received multiple inpatient doses of dose-escalated therapy had a higher percentage of colectomy during the initial hospitalization but a lower rate of perioperative complications. LIMITATIONS This study was limited by the use of retrospective data and the limited power to account for the heterogeneity of disease. CONCLUSIONS No significant difference was found in colectomy rates between patients receiving standard or dose-intensified regimens. However, dose-intensified regimens, including multiple inpatient doses given to patients with more severe disease, were not associated with a greater risk of perioperative complications. See Video Abstract at http://links.lww.com/DCR/B864 . LA TERAPIA DE RESCATE CON DOSIS INTENSIFICADA DE INFLIXIMAB EN COLITIS ULCEROSA GRAVE NO REDUCE LAS TASAS DE COLECTOMA A CORTO PLAZO NI AUMENTA LAS COMPLICACIONES POSOPERATORIAS ANTECEDENTES:La terapia de rescate de dosis intensificada con infliximab para pacientes hospitalizados con colitis ulcerosa se ha vuelto cada vez más popular en los últimos años. Sin embargo, existe un debate en curso sobre la eficacia de estos regímenes para reducir la tasa de colectomía y los riesgos asociados a una mayor exposición al infliximab.OBJETIVO:El propósito de este estudio fue comparar las tasas de colectomía y complicaciones posoperatorias en pacientes hospitalizados con colitis ulcerosa grave que recibieron terapia estándar de inducción de infliximab (3 dosis de 5 mg/kg en las semanas 0, 2, 6) y regímenes de dosis intensificada que incluyen una dosificación más alta basada en el peso o intervalo más rápido.DISEÑO:Fue un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un hospital académico de tercer nivel.PACIENTES:Un total de 145 pacientes adultos que recibieron terapia de rescate con infliximab para el tratamiento de la colitis ulcerosa entre 2008 y 2020.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado principal fue la tasa de colectomía dentro de los 3 meses posteriores a la terapia de rescate. Los resultados secundarios incluyen tasas de colectomía a mediano plazo, así como las complicaciones perioperatorias en pacientes que reciben colectomía dentro de los 3 meses posteriores al inicio de infliximab de rescate.RESULTADOS:La proporción de regímenes de dosis intensificada aumentó con el tiempo. Las tasas de colectomía de 3 meses no ajustadas fueron del 14% en los pacientes que recibieron dosis estándar de infliximab de rescate, del 16% en los pacientes que recibieron una dosis única escalonada y del 24% en los pacientes que recibieron múltiples dosis hospitalarias escalonadas. Estas tasas no fueron estadísticamente significativas. De los pacientes que requirieron colectomía dentro de los 3 meses posteriores al rescate de infliximab, aquellos que recibieron terapia de múltiples dosis hospitalarias escalonadas tuvieron un mayor porcentaje de colectomía durante la hospitalización inicial pero una menor tasa de complicaciones perioperatorias.LIMITACIONES:Datos retrospectivos y poder limitado para explicar la heterogeneidad de la enfermedad.CONCLUSIONES:No se encontraron diferencias significativas en las tasas de colectomía entre los pacientes que recibieron regímenes estándar o de dosis intensificada. Sin embargo, los regímenes de dosis intensificadas, incluidas múltiples dosis hospitalarias administradas a pacientes con enfermedad más grave, no se asociaron con un mayor riesgo de complicaciones perioperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B864 . (Traducción-Dr. Ingrid Melo ).
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Zhang T, Zhang B, Tian W, Wang F, Zhang J, Ma X, Wei Y, Tang X. Research trends in ulcerative colitis: A bibliometric and visualized study from 2011 to 2021. Front Pharmacol 2022; 13:951004. [PMID: 36199683 PMCID: PMC9529236 DOI: 10.3389/fphar.2022.951004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/19/2022] [Indexed: 12/07/2022] Open
Abstract
Background: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease with repeated relapses and remissions. Despite decades of effort, numerous aspects, including the initiating event and pathogenesis of UC, still remain ambiguous, which requires ongoing investigation. Given the mass of publications on UC, there are multidimensional challenges to evaluating the scientific impact of relevant work and identifying the current foci of the multifaceted disease. Accordingly, herein, we aim to assess the global growth of UC research production, analyze patterns of research areas, and evaluate trends in this area. Methods: The Web of Science Core Collection of Clarivate Analytics was searched for articles related to UC published from 2011 to 2021. Microsoft Office Excel 2019 was used to visualize the number of publications over time. Knowledge maps were generated using CiteSpace and VOSviewer to analyze collaborations among countries, institutions, and authors and to present the journey of UC research as well as to reveal the current foci of UC research. Results: A total of 5,088 publications were evaluated in the present study. China had the most publications (1,099, 22.5%). Univ Calif San Diego was the most productive institution (126, 2.48%). William J Sandborn published the greatest number of articles (100, 1.97%). Toshifumi Hibi was the most influential author in the field with a betweenness centrality of 0.53. Inflammatory bowel diseases was identified as the most prolific journal (379, 7.45%). Gastroenterology was the most co-cited journal (3,730, 4.02%). “Vedolizumab,” “tofacitinib,” “Faecalibacterium prausnitzii,” “fecal microbiota transplantation (FMT),” “toll-like receptor 4,” and “nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome” were considered the hot topics. Conclusion: In UC research, manuscripts that had high impacts on the scientific community provided an evidence base. UC therapy has entered the era of personalized and precision therapy. As research on FMT, anti-integrin antibodies, Janus kinase inhibitors, and anti-tumor necrosis factor drugs continues to grow, their use in the clinical setting may also expand.
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Affiliation(s)
- Tai Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Beihua Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Wende Tian
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Fengyun Wang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Jiaqi Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Xiangxue Ma
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Yuchen Wei
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Xudong Tang
- China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Xudong Tang,
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Ferretti F, Cannatelli R, Monico MC, Maconi G, Ardizzone S. An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis. J Clin Med 2022; 11:jcm11092302. [PMID: 35566428 PMCID: PMC9104748 DOI: 10.3390/jcm11092302] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/10/2022] [Accepted: 04/18/2022] [Indexed: 12/17/2022] Open
Abstract
The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients.
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Chen X, Jiang L, Han W, Bai X, Ruan G, Guo M, Zhou R, Liang H, Yang H, Qian J. Artificial Neural Network Analysis-Based Immune-Related Signatures of Primary Non-Response to Infliximab in Patients With Ulcerative Colitis. Front Immunol 2022; 12:742080. [PMID: 34992592 PMCID: PMC8724249 DOI: 10.3389/fimmu.2021.742080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 11/10/2021] [Indexed: 12/23/2022] Open
Abstract
Infliximab (IFX) is an effective medication for ulcerative colitis (UC) patients. However, one-third of UC patients show primary non-response (PNR) to IFX. Our study analyzed three Gene Expression Omnibus (GEO) datasets and used the RobustRankAggreg (RRA) algorithm to assist in identifying differentially expressed genes (DEGs) between IFX responders and non-responders. Then, an artificial intelligence (AI) technology, artificial neural network (ANN) analysis, was applied to validate the predictive value of the selected genes. The results showed that the combination of CDX2, CHP2, HSD11B2, RANK, NOX4, and VDR is a good predictor of patients' response to IFX therapy. The range of repeated overall area under the receiver-operating characteristic curve (AUC) was 0.850 ± 0.103. Moreover, we used an independent GEO dataset to further verify the value of the six DEGs in predicting PNR to IFX, which has a range of overall AUC of 0.759 ± 0.065. Since protein detection did not require fresh tissue and can avoid multiple biopsies, our study tried to discover whether the key information, analyzed by RNA levels, is suitable for protein detection. Therefore, immunohistochemistry (IHC) staining of colonic biopsy tissues from UC patients treated with IFX and a receiver-operating characteristic (ROC) analysis were used to further explore the clinical application value of the six DEGs at the protein level. The IHC staining of colon tissues from UC patients confirmed that VDR and RANK are significantly associated with IFX efficacy. Total IHC scores lower than 5 for VDR and lower than 7 for RANK had an AUC of 0.828 (95% CI: 0.665-0.991, p = 0.013) in predicting PNR to IFX. Collectively, we identified a predictive RNA model for PNR to IFX and explored an immune-related protein model based on the RNA model, including VDR and RANK, as a predictor of IFX non-response, and determined the cutoff value. The result showed a connection between the RNA and protein model, and both two models were available. However, the composite signature of VDR and RANK is more conducive to clinical application, which could be used to guide the preselection of patients who might benefit from pharmacological treatment in the future.
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Affiliation(s)
- Xuanfu Chen
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Lingjuan Jiang
- Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei Han
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Xiaoyin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Mingyue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Runing Zhou
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Haozheng Liang
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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Zafer M, Zhang H, Dwadasi S, Goens D, Paknikar R, Dalal S, Cohen RD, Pekow J, Rubin DT, Sakuraba A, Micic D. A Clinical Predictive Model for One-year Colectomy in Adults Hospitalized for Severe Ulcerative Colitis. CROHN'S & COLITIS 360 2021; 4:otab082. [PMID: 36777555 PMCID: PMC9802419 DOI: 10.1093/crocol/otab082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Indexed: 11/13/2022] Open
Abstract
Background Models to predict colectomy in ulcerative colitis (UC) are valuable for identification, clinical management, and follow-up of high-risk patients. Our aim was to develop a clinical predictive model based on admission data for one-year colectomy in adults hospitalized for severe UC. Methods We performed a retrospective analysis of patients hospitalized at a tertiary academic center for management of severe UC from 1/2013 to 4/2018. Multivariate regression was performed to identify individual predictors of one-year colectomy. Outcome probabilities of colectomy based on the prognostic score were estimated using a bootstrapping technique. Results Two hundred twenty-nine individuals were included in the final analytic cohort. Four independent variables were associated with one-year colectomy which were incorporated into a point scoring system: (+) 1 for single class biologic exposure prior to admission; (+) 2 for multiple classes of biologic exposure; (+) 1 for inpatient salvage therapy with cyclosporine or a TNF-alpha inhibitor; (+) 1 for age <40. The risk probabilities of colectomy within one year in patients assigned scores 1, 2, 3, and 4 were 9.4% (95% CI, 1.7-17.2), 33.7% (95% CI, 23.9-43.5), 58.5% (95% CI, 42.9-74.1), 75.0% (95% CI, 50.5-99.5). An assigned score of zero was a perfect predictor of no colectomy. Conclusion Risk factors most associated with one-year colectomy for severe UC included: prior biologic exposure, need for inpatient salvage therapy, and younger age. We developed a simple scoring system using these variables to identify and stratify patients during their index hospitalization.
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Affiliation(s)
- Maryam Zafer
- Department of Internal Medicine, University of Chicago Medicine, Chicago, IL, USA
| | - Hui Zhang
- The Center for Health and the Social Sciences, University of Chicago, Chicago, IL, USA
| | - Sujaata Dwadasi
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - Donald Goens
- Department of Internal Medicine, University of Chicago Medicine, Chicago, IL, USA
| | - Raghavendra Paknikar
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - Sushila Dalal
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - Russell D Cohen
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - Joel Pekow
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - David T Rubin
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - Atsushi Sakuraba
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - Dejan Micic
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA,Address correspondence to: Dejan Micic, MD, 5841 South Maryland Avenue, MC4076, Chicago, IL 60637, USA. Telephone: 773-702-9200 ()
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Cai Z, Wang S, Li J. Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front Med (Lausanne) 2021; 8:765474. [PMID: 34988090 PMCID: PMC8720971 DOI: 10.3389/fmed.2021.765474] [Citation(s) in RCA: 233] [Impact Index Per Article: 58.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 11/29/2021] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD), as a global disease, has attracted much research interest. Constant research has led to a better understanding of the disease condition and further promoted its management. We here reviewed the conventional and the novel drugs and therapies, as well as the potential ones, which have shown promise in preclinical studies and are likely to be effective future therapies. The conventional treatments aim at controlling symptoms through pharmacotherapy, including aminosalicylates, corticosteroids, immunomodulators, and biologics, with other general measures and/or surgical resection if necessary. However, a considerable fraction of patients do not respond to available treatments or lose response, which calls for new therapeutic strategies. Diverse therapeutic options are emerging, involving small molecules, apheresis therapy, improved intestinal microecology, cell therapy, and exosome therapy. In addition, patient education partly upgrades the efficacy of IBD treatment. Recent advances in the management of IBD have led to a paradigm shift in the treatment goals, from targeting symptom-free daily life to shooting for mucosal healing. In this review, the latest progress in IBD treatment is summarized to understand the advantages, pitfalls, and research prospects of different drugs and therapies and to provide a basis for the clinical decision and further research of IBD.
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Affiliation(s)
- Zhaobei Cai
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
- Department of Gastroenterology and Hepatology, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Shu Wang
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Jiannan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
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Suarez-Lopez L, Shui B, Brubaker DK, Hill M, Bergendorf A, Changelian PS, Laguna A, Starchenko A, Lauffenburger DA, Haigis KM. Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation. iScience 2021; 24:103406. [PMID: 34849469 PMCID: PMC8609096 DOI: 10.1016/j.isci.2021.103406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 06/28/2021] [Accepted: 11/03/2021] [Indexed: 11/30/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are genetically complex and exhibit significant inter-patient heterogeneity in disease presentation and therapeutic response. Here, we show that mouse models of IBD exhibit variable responses to inhibition of MK2, a pro-inflammatory serine/threonine kinase, and that MK2 inhibition suppresses inflammation by targeting inflammatory monocytes and neutrophils in murine models. Using a computational approach (TransComp-R) that allows for cross-species comparison of transcriptomic features, we identified an IBD patient subgroup that is predicted to respond to MK2 inhibition, and an independent preclinical model of chronic intestinal inflammation predicted to be non-responsive, which we validated experimentally. Thus, cross-species mouse-human translation approaches can help to identify patient subpopulations in which to deploy new therapies.
MK2 kinase inhibition shows variable efficacy in different IBD mouse models TCT and TNFΔARE mice express distinct inflammatory and MK2-responsive genes “Response to MK2i” signature is enriched in monocytes and neutrophils Cross-species modeling identifies patient groups potentially responsive to MK2i
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Affiliation(s)
- Lucia Suarez-Lopez
- Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
- Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
| | - Bing Shui
- Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
- Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
| | - Douglas K. Brubaker
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47906, USA
- Regenstrief Center for Healthcare Engineering, Purdue University, West Lafayette, IN 47906, USA
| | - Marza Hill
- Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
| | - Alexander Bergendorf
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47906, USA
| | - Paul S. Changelian
- Aclaris Therapeutics, Inc., 4320 Forest Park Avenue, St. Louis, MO 63108, USA
| | - Aisha Laguna
- Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
| | - Alina Starchenko
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Douglas A. Lauffenburger
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Kevin M. Haigis
- Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
- Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
- Corresponding author
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Hishinuma K, Moroi R, Okamoto D, Shimoyama Y, Kuroha M, Shiga H, Kakuta Y, Kinouchi Y, Masamune A. Analysis of the Long-Term Prognosis in Japanese Patients with Ulcerative Colitis Treated with New Therapeutic Agents and the Correlation between Prognosis and Disease Susceptibility Loci. Inflamm Intest Dis 2021; 6:154-164. [PMID: 34722645 DOI: 10.1159/000518371] [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] [Received: 03/31/2021] [Accepted: 07/07/2021] [Indexed: 11/19/2022] Open
Abstract
Background New therapeutic agents, including biologics and small-molecule drugs, are widely used to treat ulcerative colitis (UC). This study evaluates long-term prognosis in Japanese patients treated with these agents and the association between prognosis and genetic susceptibility to UC. Methods We evaluated surgery-free rates using the Kaplan-Meier method in the total cohort and in patients treated with prednisolone and new therapeutic agents. Multivariate analysis was performed to identify clinical factors affecting surgical rates using Cox's proportional hazard model. The rate of use of new therapeutic agents was compared using the Kaplan-Meier method, and multivariate analysis was conducted to investigate the correlation between the single-nucleotide polymorphism (SNP) rs117506082 and long-term prognosis. Results Surgery-free survival decreased over time. There was no significant difference in this parameter between patients who were administered prednisolone and those who were administered new therapeutic agents. Poor response to prednisolone and treatment without topical 5-aminosalicylic acid were poor prognostic factors. Shorter time from diagnosis to initiation of treatment with new therapeutic agents was a risk factor for colectomy. The AA genotype of SNP rs117506082 was associated with a shorter time to surgery and increased use of new therapeutic agents. Conclusions The use of new therapeutic agents might improve long-term prognosis in patients with more severe UC. Previously identified genetic risk factors were not significantly associated with a higher rate of colectomy.
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Affiliation(s)
- Kasumi Hishinuma
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
| | - Rintaro Moroi
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
| | - Daisuke Okamoto
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
| | - Yusuke Shimoyama
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
| | - Masatake Kuroha
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
| | - Hisashi Shiga
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
| | - Yoichi Kakuta
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
| | | | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
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Eriksson C, Visuri I, Vigren L, Nilsson L, Kärnell A, Hjortswang H, Bergemalm D, Almer S, Hertervig E, Karlén P, Strid H, Halfvarson J. Clinical effectiveness of golimumab in ulcerative colitis: a prospective multicentre study based on the Swedish IBD Quality Register, SWIBREG. Scand J Gastroenterol 2021; 56:1304-1311. [PMID: 34415803 DOI: 10.1080/00365521.2021.1963466] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Clinical trials demonstrated that golimumab is effective in anti-TNF naïve patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. MATERIALS AND METHODS This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore ≥2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by ≥3 points or 30% from baseline) and remission (defined as a Mayo score of ≤2 with no individual subscores >1). RESULTS Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) µg/g to 90 (34-169) µg/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5‒1188.9). CONCLUSIONS The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis.
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Affiliation(s)
- Carl Eriksson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.,Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Isabella Visuri
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | | | - Linda Nilsson
- Department of Gastroenterology, Danderyd Hospital, Stockholm, Sweden
| | | | - Henrik Hjortswang
- Department of Gastroenterology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Daniel Bergemalm
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | | | - Sven Almer
- Karolinska Institutet, Department of Medicine, Solna, IBD-Unit, Division of Gastroenterology, Karolinska University Hospital, Stockholm, Sweden
| | - Erik Hertervig
- Department of Gastroenterology, Skåne University Hospital, Lund, Sweden
| | - Per Karlén
- Department of Gastroenterology, Danderyd Hospital, Stockholm, Sweden
| | - Hans Strid
- Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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Lang-Schwarz C, Angeloni M, Agaimy A, Atreya R, Becker C, Dregelies T, Danese S, Fléjou JF, Gaßler N, Grabsch HI, Hartmann A, Kamarádová K, Kühl AA, Lauwers GY, Lugli A, Nagtegaal I, Neurath MF, Oberhuber G, Peyrin-Biroulet L, Rath T, Riddell R, Rubio CA, Sheahan K, Siegmund B, Tilg H, Villanacci V, Westerhoff M, Ferrazzi F, Vieth M. Validation of the 'Inflammatory Bowel Disease-Distribution, Chronicity, Activity [IBD-DCA] Score' for Ulcerative Colitis and Crohn´s Disease. J Crohns Colitis 2021; 15:1621-1630. [PMID: 33773497 PMCID: PMC8495487 DOI: 10.1093/ecco-jcc/jjab055] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Histological scoring plays a key role in the assessment of disease activity in ulcerative colitis [UC] and is also important in Crohn´s disease [CD]. Currently, there is no common scoring available for UC and CD. We aimed to validate the Inflammatory Bowel Disease [IBD]-Distribution [D], Chronicity [C], Activity [A] score [IBD-DCA score] for histological disease activity assessment in IBD. METHODS Inter- and intra-rater reliability were assessed by 16 observers on biopsy specimens from 59 patients with UC and 25 patients with CD. Construct validity and responsiveness to treatment were retrospectively evaluated in a second cohort of 30 patients. RESULTS Inter-rater reliability was moderate to good for the UC cohort (intraclass correlation coefficients [ICCs] = 0.645, 0.623, 0.767 for D, C, and A, respectively) and at best moderate for the CD cohort [ICC = 0.690, 0.303, 0.733 for D, C, and A, respectively]. Intra-rater agreement ranged from good to excellent in both cohorts. Correlation with the Nancy Histological Index [NHI] was moderate and strong with the Simplified Geboes Score [SGS] and a Visual Analogue Scale [VAS], respectively. Large effect sizes were obtained for all three parameters. External responsiveness analysis revealed correlated changes between IBD-DCA score and NHI, SGS and VAS. CONCLUSIONS The IBD-DCA score is a simple histological activity score for UC and CD, agreed and validated by a large group of IBD specialists. It provides reliable information on treatment response. Therefore, it has potential value for use in routine diagnostics as well as clinical studies.
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Affiliation(s)
| | - Miriam Angeloni
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
| | - Abbas Agaimy
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
| | - Raja Atreya
- Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander-University, Erlangen, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | - Christoph Becker
- Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander-University, Erlangen, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | | | - Silvio Danese
- Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Jean-François Fléjou
- Pathology Department, Saint-Antoine Hospital, Pierre et Marie Curie University, Paris, France
| | - Nikolaus Gaßler
- Institute for Legal Medicine, Section Pathology, University Hospital, Jena, Germany
| | - Heike I Grabsch
- Department of Pathology, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
- Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK
| | - Arndt Hartmann
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
| | - Kateřina Kamarádová
- Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic
| | - Anja A Kühl
- Charité ‐ Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | | | | | - Iris Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Markus F Neurath
- Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander-University, Erlangen, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | - Georg Oberhuber
- Institute of Pathology, Tirol Kliniken, Innsbruck, Austria
- Institute of Pathology, Patho im Zentrum, St. Pölten, Austria
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre, France
| | - Timo Rath
- Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander-University, Erlangen, Germany
| | - Robert Riddell
- Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Carlos A Rubio
- Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - Kieran Sheahan
- Department of Pathology & Centre for Colorectal Disease, St Vincent´s University Hospital and University College, Dublin, Ireland
| | - Britta Siegmund
- Medical Department [Gastroenterology, Infectiology, Rheumatology], Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | | | - Maria Westerhoff
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Fulvia Ferrazzi
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth GmbH, Bayreuth, Germany
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
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38
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Visuri I, Eriksson C, Olén O, Cao Y, Mårdberg E, Grip O, Gustavsson A, Hjortswang H, Karling P, Montgomery S, Myrelid P, Ludvigsson JF, Halfvarson J. Predictors of drug survival: A cohort study comparing anti-tumour necrosis factor agents using the Swedish inflammatory bowel disease quality register. Aliment Pharmacol Ther 2021; 54:931-943. [PMID: 34286871 DOI: 10.1111/apt.16525] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/25/2021] [Accepted: 06/26/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. AIMS To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. METHODS Biologic-naïve patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). RESULTS In Crohn's disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration ≥10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates. CONCLUSIONS Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohn's disease, suggests a potential difference between the two drugs.
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39
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Saito D, Matsuura M, Ozaki R, Tokunaga S, Minowa S, Mitsui T, Miura M, Sakuraba A, Hayashida M, Miyoshi J, Hisamatsu T. Clinical response of vedolizumab at week 6 predicted endoscopic remission at week 24 in ulcerative colitis. JGH OPEN 2021; 5:1056-1062. [PMID: 34584975 PMCID: PMC8454470 DOI: 10.1002/jgh3.12630] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/10/2021] [Accepted: 07/25/2021] [Indexed: 12/20/2022]
Abstract
Background and Aim Vedolizumab is a humanized monoclonal antibody that selectively inhibits the migration of gut‐homing memory T cells into the intestinal submucosa by antagonizing the interaction of α4β7 integrin with MAdCAM‐1. Vedolizumab is employed for ulcerative colitis with moderate to severe activity; however, predictors of its clinical efficacy have not been established in real‐world clinical practice. We investigated the clinical characteristics predicting vedolizumab efficacy. Methods This was a single‐center, retrospective, observational study that enrolled patients with ulcerative colitis at Kyorin University Hospital. Fifty‐two consecutive patients who started vedolizumab induction therapy and were tracked for minimum 14 weeks between August 2018 and February 2021 were included. Clinical and endoscopic disease activities were scored at baseline and at weeks 2, 6, and 14 with the Lichtiger index and at baseline and week 24 with the Mayo endoscopic subscore, respectively. Clinical remission, clinical response, and endoscopic remission were defined as Lichtiger index of ≤3, Lichtiger index of ≤10 with a reduction of minimum 3 points from baseline, and Mayo endoscopic subscore of ≤1, respectively. Results In these cases, clinical response/remission rates at weeks 2, 6, and 14 were 26.9%/15.3%, 50.0%/46.3%, and 57.6%/50.0%, respectively. The endoscopic remission rate at week 24 was 60%. The clinical response at week 6 was significantly associated with endoscopic remission at week 24 after starting vedolizumab. Conclusions In vedolizumab treatment for ulcerative colitis, the clinical response at week 6 can be a predictor for endoscopic remission at week 24.
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Affiliation(s)
- Daisuke Saito
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Ryo Ozaki
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Sotaro Tokunaga
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Shintaro Minowa
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Tatsuya Mitsui
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Miki Miura
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Akihito Sakuraba
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Mari Hayashida
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Jun Miyoshi
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Tokyo Japan
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40
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Soriano CR, Powell CR, Chiorean MV, Simianu VV. Role of hospitalization for inflammatory bowel disease in the post-biologic era. World J Clin Cases 2021; 9:7632-7642. [PMID: 34621815 PMCID: PMC8462259 DOI: 10.12998/wjcc.v9.i26.7632] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/17/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Treatment for inflammatory bowel disease (IBD) often requires specialized care. While much of IBD care has shifted to the outpatient setting, hospitalizations remain a major site of healthcare utilization and a sizable proportion of patients with inflammatory bowel disease require hospitalization or surgery during their lifetime. In this review, we approach IBD care from the population-level with a specific focus on hospitalization for IBD, including the shifts from inpatient to outpatient care, the balance of emergency and elective hospitalizations, regionalization of specialty IBD care, and contribution of surgery and endoscopy to hospitalized care.
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Affiliation(s)
- Celine R Soriano
- Department of Surgery, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
| | - Charleston R Powell
- Department of Internal Medicine, Madigan Army Medical Center, Tacoma, WA 98431, United States
| | - Michael V Chiorean
- Department of Gastroenterology, Swedish Medical Center, Seattle, WA 98109, United States
| | - Vlad V Simianu
- Department of Surgery, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
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41
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Mo A, Nagpal S, Gettler K, Haritunians T, Giri M, Haberman Y, Karns R, Prince J, Arafat D, Hsu NY, Chuang LS, Argmann C, Kasarskis A, Suarez-Farinas M, Gotman N, Mengesha E, Venkateswaran S, Rufo PA, Baker SS, Sauer CG, Markowitz J, Pfefferkorn MD, Rosh JR, Boyle BM, Mack DR, Baldassano RN, Shah S, LeLeiko NS, Heyman MB, Griffiths AM, Patel AS, Noe JD, Davis Thomas S, Aronow BJ, Walters TD, McGovern DPB, Hyams JS, Kugathasan S, Cho JH, Denson LA, Gibson G. Stratification of risk of progression to colectomy in ulcerative colitis via measured and predicted gene expression. Am J Hum Genet 2021; 108:1765-1779. [PMID: 34450030 DOI: 10.1016/j.ajhg.2021.07.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 07/26/2021] [Indexed: 12/13/2022] Open
Abstract
An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.
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Affiliation(s)
- Angela Mo
- Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Sini Nagpal
- Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Kyle Gettler
- Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA
| | - Talin Haritunians
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Mamta Giri
- Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA
| | - Yael Haberman
- Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv 5265601, Israel
| | - Rebekah Karns
- Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | | | - Dalia Arafat
- Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Nai-Yun Hsu
- Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA
| | - Ling-Shiang Chuang
- Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA
| | - Carmen Argmann
- Icahn Institute for Data Science and Genomic Technology, and Department of Population Health Science and Policy, Mount Sinai School of Medicine, New York City, NY 10029, USA
| | - Andrew Kasarskis
- Icahn Institute for Data Science and Genomic Technology, and Department of Population Health Science and Policy, Mount Sinai School of Medicine, New York City, NY 10029, USA
| | - Mayte Suarez-Farinas
- Icahn Institute for Data Science and Genomic Technology, and Department of Population Health Science and Policy, Mount Sinai School of Medicine, New York City, NY 10029, USA
| | - Nathan Gotman
- University of North Carolina, Chapel Hill, NC 27516, USA
| | - Emebet Mengesha
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | | | - Paul A Rufo
- Harvard University-Children's Hospital Boston, Boston, MA 02115, USA
| | - Susan S Baker
- Women & Children's Hospital of Buffalo, Buffalo, NY 14222, USA
| | | | - James Markowitz
- Cohen Children's Medical Center of New York, New Hyde Park, NY 11040, USA
| | | | - Joel R Rosh
- Goryeb Children's Hospital-Atlantic Health, Morristown, NJ 07960, USA
| | | | - David R Mack
- Children's Hospital of East Ontario, Ottawa, ON K1P 1J1, Canada
| | | | - Sapana Shah
- Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA
| | - Neal S LeLeiko
- Department of Pediatrics, Columbia University, New York City, NY 10032, USA
| | - Melvin B Heyman
- University of California at San Francisco, San Francisco, CA 94143, USA
| | | | | | - Joshua D Noe
- Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | | | - Bruce J Aronow
- Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | | | - Dermot P B McGovern
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Jeffrey S Hyams
- Connecticut Children's Medical Center, Hartford, CT 06106, USA
| | | | - Judy H Cho
- Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA
| | - Lee A Denson
- Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Greg Gibson
- Georgia Institute of Technology, Atlanta, GA 30332, USA.
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Truong A, Zaghiyan KN, Mirocha J, Melmed GY, McGovern DPB, Syal G, Ha CY, Targan SR, Fleshner PR. Antitumour necrosis factor therapy is associated with de novo Crohn's disease after ileal pouch-anal anastomosis. Colorectal Dis 2021; 23:2416-2424. [PMID: 34157179 PMCID: PMC8440372 DOI: 10.1111/codi.15772] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 05/02/2021] [Accepted: 05/09/2021] [Indexed: 12/12/2022]
Abstract
AIM Tumour necrosis factor inhibitors (TNFi) have revolutionized the management of moderate to severe ulcerative colitis (UC) since their approval for UC in 2005. However, many patients ultimately require surgery with ileal pouch-anal anastomosis (IPAA). Development of de novo Crohn's disease (CD) following IPAA is an increasingly common and devastating complication, sometimes progressing to pouch failure. The aim of this study was to evaluate the association of preoperative TNFi exposure and the development of de novo CD after IPAA. METHOD A prospective single-centre inflammatory bowel disease (IBD) registry was searched for consecutive patients with UC undergoing IPAA during a 25-year period ending July 2018. Patients with preoperative CD or IBD-unclassified were excluded. De novo CD was diagnosed upon endoscopic evidence of five or more mucosal ulcers proximal to the ileal pouch any time after surgery and/or pouch fistula occurring more than three months after ileostomy closure. RESULTS The study cohort consisted of 400 patients with a median follow-up of 44.0 (IQR 11-113) months. Sixty-two (16%) patients developed de novo CD 28.0 (IQR 6-67) months following ileostomy closure. Survival analysis of TNFi era patients revealed a significant increase in de novo CD risk in those with preoperative TNFi exposure. Multivariable proportional hazards modelling revealed two independent predictors for de novo CD development: older age was protective (HR 0.89 per 5-year increase; P = 0.009) and preoperative TNFi exposure was hazardous (HR 2.10; P = 0.011). CONCLUSION This prospective study is the first to suggest an association between preoperative TNFi exposure and the development of de novo CD.
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Affiliation(s)
- Adam Truong
- Division of Colorectal Surgery, Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Karen N Zaghiyan
- Division of Colorectal Surgery, Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - James Mirocha
- Department of Biostatistics, Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Gil Y Melmed
- Department of Gastroenterology - Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Dermot PB McGovern
- Department of Gastroenterology - Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Gaurav Syal
- Department of Gastroenterology - Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Christina Y Ha
- Department of Gastroenterology - Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Stephan R Targan
- Department of Gastroenterology - Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Phillip R Fleshner
- Division of Colorectal Surgery, Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
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Battat R, Lukin D, Scherl EJ, Pola S, Kumar A, Okada L, Yang L, Jain A, Siegel CA. Immunogenicity of Tumor Necrosis Factor Antagonists and Effect of Dose Escalation on Anti-Drug Antibodies and Serum Drug Concentrations in Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:1443-1451. [PMID: 33252119 DOI: 10.1093/ibd/izaa313] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Infliximab and adalimumab concentrations are associated with important outcomes in inflammatory bowel disease (IBD). Antibodies to infliximab (ATI) and adalimumab (ATA) are associated with reduced drug concentrations and worse outcomes. Because the efficacy of dose escalation to overcome antibodies is unclear, we assessed the impact of this strategy to overcome immunogenicity in IBD. METHODS Infliximab and adalimumab dosing, drug, and antibody concentrations were extracted from a database of patients with IBD having specimens collected for therapeutic drug monitoring. The primary outcome compared proportions with either infliximab ≥5 μg/mL or adalimumab ≥7.5 μg/mL and undetectable antibodies between dose-escalated and non-escalated patients. Area under the receiver operating characteristic curve analyses determined antibody concentrations below which dose escalation was associated with the primary outcome. RESULTS The study included 63,176 patients treated with infliximab and 46,429 patients treated with adalimumab. We detected ATI and ATA in 23.6% (n = 14,900) of patients treated with infliximab and 19.6% (n = 9101) of patients treated with adalimumab. In patients with ATI, infliximab dose escalation (n = 453) yielded higher proportions achieving the primary outcome (47.5% vs 30.9%; P < 0.001), greater drug concentration increases (5.9 μg/mL vs 0.2 μg/mL; P < 0.001), and ATI reductions (4.3 U/mL vs 1.9 U/mL; P = 0.002) compared to no escalation (n = 204). An ATI threshold of 8.55 U/mL was associated with achieving the primary outcome with dose escalation (area under the curve = 0.66). For patients with ATI ≤8.55 U/mL (n = 274), higher proportions (59.1% vs 29.6%; P < 0.001) achieved the primary outcome compared with those with ATI >8.55 U/mL (n = 179). No patients treated with adalimumab achieved the primary outcome (0/390), regardless of dose escalation (n = 87). CONCLUSION Dose escalation increased drug concentrations and eliminated antibodies with infliximab but not adalimumab. Initial ATI ≤8.55 U/mL was associated with increased efficacy of dose escalation using this assay.
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Affiliation(s)
- Robert Battat
- Jill Roberts Center for IBD, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA
| | - Dana Lukin
- Jill Roberts Center for IBD, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA
| | - Ellen J Scherl
- Jill Roberts Center for IBD, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA
| | - Suresh Pola
- Kaiser Permanente San Diego, San Diego, California, USA
| | - Anand Kumar
- Jill Roberts Center for IBD, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA
| | - Lauren Okada
- Prometheus Biosciences, San Diego, California, USA
| | - Lei Yang
- Prometheus Biosciences, San Diego, California, USA
| | - Anjali Jain
- Prometheus Biosciences, San Diego, California, USA
| | - Corey A Siegel
- Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
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Sicilia B, García-López S, González-Lama Y, Zabana Y, Hinojosa J, Gomollón F. GETECCU 2020 guidelines for the treatment of ulcerative colitis. Developed using the GRADE approach. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 43 Suppl 1:1-57. [PMID: 32807301 DOI: 10.1016/j.gastrohep.2020.07.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Since the first edition of the Guidelines was published in 2013, much information has been generated around the treatment of ulcerative colitis, and new drugs and action protocols have been introduced. Clinical practice has changed substantially, warranting new approaches and a comprehensive review and update of the evidence. MATERIAL AND METHODS Once again, we used the GRADE approach, supported by an electronic tool (https://gradepro.org). The clinical scenarios are the same as in the previous version (induction and maintenance in severe and mild-moderate flare-ups), as are the variables and their evaluation. However, in the updated guidelines, three questions have been deleted, 14 added and 30 maintained, making a total of 44 clinical questions. After an exhaustive review of the evidence, the recommendations are now updated. RESULTS Of the 44 questions analysed, no recommendation could be established in two due to the very low quality of the evidence, while in the other 42, based on different degrees of quality of evidence, recommendations were made according to the GRADE system. In 25 of these questions the final recommendation is strongly in favour, in six strongly against, in seven weakly in favour and in four weakly against. According to the scenarios and recommendations, six algorithms are proposed as a simple guide for practical decision-making. CONCLUSIONS The aim of this update of the 2013 guidelines is to provide answers, based on the GRADE approach, to the different questions we ask ourselves daily when deciding the most appropriate treatment for our patients with ulcerative colitis in the different clinical scenarios.
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Affiliation(s)
- Beatriz Sicilia
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Burgos, España
| | - Santiago García-López
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, España.
| | - Yago González-Lama
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo Hospital Universitario Mútua Terrassa Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
| | - Joaquín Hinojosa
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital de Manises, Valencia, España
| | - Fernando Gomollón
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Instituto de Investigaciones Sanitarias de Aragón, Hospital Clínico Universitario Lozano Blesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Zaragoza, España
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Pabari RM, Tambuwala MM, Lajczak-McGinley N, Aljabali A, Kirby BP, Keely S, Ramtoola Z. Novel polyurethane based particulate formulations of infliximab reduce inflammation in DSS induced murine model of colitis - A preliminary study. Int J Pharm 2021; 604:120717. [PMID: 34015378 DOI: 10.1016/j.ijpharm.2021.120717] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/13/2021] [Accepted: 05/13/2021] [Indexed: 11/19/2022]
Abstract
Our recent study showed that novel infliximab (INF) loaded polyesterurethane (INF-PU) and INF-PU-PEG particulate formulations reduced inflammation in an in-vitro epithelial inflammation model. In this study we investigated therapeutic potential of novel INF-PU and INF-PU-PEG particulate formulations to reduce inflammation in a dextran sodium sulfate (DSS) induced murine model of colitis. Severity of colitis was assessed by measurement of disease activity index (DAI) score, inflammatory markers (neutrophil infiltration, TNFα) and histological score. Treatment groups orally administered with INF-PU and INF-PU-PEG particulate formulations showed improvement in the clinical signs of colitis, similar to that observed with intraperitoneally administered INF, in both, moderate and severe DSS induced colitis model. This was related to a significant reduction in inflammatory cytokines, resulting in a significant reduction in histological score (ANOVA; p < 0.05), indicative of mucosal healing, a key goal of IBD therapy. This could be attributed to its targeted delivery to the inflamed colon and higher permeation of these particulate formulations across the inflamed colonic mucosa, as observed by the confocal images, resulting in local inhibition of TNFα at its site of production. These promising preliminary results warrant further investigation of orally administered INF and its novel particulate formulations in a wider preclinical study.
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Affiliation(s)
- Ritesh M Pabari
- RCSI, University of Medicine and Health Sciences, Dublin, Ireland.
| | - Murtaza M Tambuwala
- School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, County, Londonderry BT52 1SA, Northern Ireland, United Kingdom
| | | | - Alaa Aljabali
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Yarmouk University, Irbid, Jordan
| | - Brian P Kirby
- RCSI, University of Medicine and Health Sciences, Dublin, Ireland
| | - Stephen Keely
- Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
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Jenkinson PW, Plevris N, Lyons M, Grant R, Fulforth J, Kirkwood K, Arnott ID, Wilson D, Watson AJM, Jones GR, Lees CW. Analysis of colectomy rates for ulcerative colitis in pre- and postbiological eras in Lothian, Scotland. Colorectal Dis 2021; 23:1175-1183. [PMID: 33350054 DOI: 10.1111/codi.15491] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 10/30/2020] [Accepted: 12/07/2020] [Indexed: 12/15/2022]
Abstract
AIM Biological treatment is effective in maintaining remission in ulcerative colitis (UC), although the effect on colectomy rates remains unclear. In the UK the use of antitumour necrosis factor and anti-α4β7 treatments for maintenance therapy in UC was restricted until 2015. The aim of this study was to describe the impact that this change in the prescribing of biologicals had on colectomy rates for UC. METHOD All patients (adult and paediatric) with a diagnosis of UC who received maintenance biological treatment and/or underwent a colectomy in Lothian, Scotland between 2005 and 2018 were identified. Linear and segmental regression analyses were used to identify the annual percentage change (APC) and temporal trends (statistical joinpoints) in biological prescription and colectomy rates. RESULTS Rates of initiation of maintenance biological therapy increased from 0.05 per 100 UC patients in 2005 to 1.26 in 2018 (p < 0.001). Colectomy rates per 100 UC patients fell from 1.47 colectomies in 2005 to 0.44 in 2018 (p < 0.001). The APC for colectomy decreased by 4.1% per year between 2005 and 2014 and by 18.9% between 2014 and 2018. Temporal trend analysis (2005-2018) identified a significant joinpoint in colectomy rates in 2014 (p = 0.019). CONCLUSION The use of maintenance biological therapy increased sharply following the change in guidance. This has been paralleled by a significant reduction in the rates of colectomy over the same time period.
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Affiliation(s)
- Philip W Jenkinson
- The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.,Department of General Surgery, Raigmore Hospital, Inverness, UK
| | - Nikolas Plevris
- The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | | | | | - James Fulforth
- The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | - Kate Kirkwood
- Department of Histopathology, Western General Hospital, Edinburgh, UK
| | - Ian D Arnott
- The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | | | | | | | - Charlie W Lees
- The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
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Penrose HM, Iftikhar R, Collins ME, Toraih E, Ruiz E, Ungerleider N, Nakhoul H, Flemington EF, Kandil E, Shah SB, Savkovic SD. Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy. Sci Rep 2021; 11:9010. [PMID: 33907256 PMCID: PMC8079702 DOI: 10.1038/s41598-021-88489-w] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 04/08/2021] [Indexed: 12/27/2022] Open
Abstract
The heterogeneous pathobiology underlying Ulcerative Colitis (UC) is not fully understood. Using publicly available transcriptomes from adult UC patients, we identified the immune cell landscape, molecular pathways, and differentially expressed genes (DEGs) across patient cohorts and their association with treatment outcomes. The global immune cell landscape of UC tissue included increased neutrophils, T CD4 memory activated cells, active dendritic cells (DC), and M0 macrophages, as well as reduced trends in T CD8, Tregs, B memory, resting DC, and M2 macrophages. Pathway analysis of DEGs across UC cohorts demonstrated activated bacterial, inflammatory, growth, and cellular signaling. We identified a specific transcriptional signature of one hundred DEGs (UC100) that distinctly separated UC inflamed from uninflamed transcriptomes. Several UC100 DEGs, with unidentified roles in UC, were validated in primary tissue. Additionally, non-responders to anti-TNFα and anti-α4β7 therapy displayed distinct profiles of immune cells and pathways pertaining to inflammation, growth, and metabolism. We identified twenty resistant DEGs in UC non-responders to both therapies of which four had significant predictive power to treatment outcome. We demonstrated the global immune landscape and pathways in UC tissue, highlighting a unique UC signature across cohorts and a UC resistant signature with predictive performance to biologic therapy outcome.
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Affiliation(s)
- Harrison M Penrose
- Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Ave SL-79, New Orleans, LA, 70112, USA
| | - Rida Iftikhar
- Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Ave SL-79, New Orleans, LA, 70112, USA
| | - Morgan E Collins
- Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Ave SL-79, New Orleans, LA, 70112, USA
| | - Eman Toraih
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University, New Orleans, LA, 70112, USA
| | - Emmanuelle Ruiz
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University, New Orleans, LA, 70112, USA
| | - Nathan Ungerleider
- Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Ave SL-79, New Orleans, LA, 70112, USA
| | - Hani Nakhoul
- Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Ave SL-79, New Orleans, LA, 70112, USA
| | - Erik F Flemington
- Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Ave SL-79, New Orleans, LA, 70112, USA
| | - Emad Kandil
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University, New Orleans, LA, 70112, USA
| | - Shamita B Shah
- Division of Gastroenterology, Ochsner Clinic Foundation, New Orleans, LA, 70121, USA
| | - Suzana D Savkovic
- Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Ave SL-79, New Orleans, LA, 70112, USA.
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Real-life evaluation of histologic scores for Ulcerative Colitis in remission. PLoS One 2021; 16:e0248224. [PMID: 33684168 PMCID: PMC7939352 DOI: 10.1371/journal.pone.0248224] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 02/22/2021] [Indexed: 02/07/2023] Open
Abstract
Background Histological evaluation of ulcerative colitis (UC) patients has been debated ever since the first description of the disease and its role in follow-up has never been fully established. Recent evidence suggests an added benefit in accuracy when evaluating if the patient is in remission. Unfortunately, there are several different histological indices, and it is difficult to compare outcomes where different scores are applied. Histopathological evaluation is prone to subjective biases, despite the use of indices. In addition, these indices are developed by expert IBD pathologist, but applied at large, by general pathologist. Therefore, we evaluated the three most applied histological indices for UC on samples from patients in remission to compare test qualities and estimate their usefulness to identify remission by both general and GI specialized pathologist. Method Mucosal biopsies from 41 UC patients in clinical and endoscopic remission were collected as part of a larger study on UC. Three pathologists blinded to the patients’ clinical status evaluated them using Geboes score (GS), Nancy Index (NI) and Robarts Histopathological Index (RHI). We calculated the agreement between the pathologists using Inter-class correlation (ICC) and visualized it with ICC-plots and Bland-Altman plots. Association between clinical factors and histological category were analysed by Fisher’s exact test. Results The ICC value for GS, RHI and NI were 0.85, 0.73 and 0.70 respectively. The limits of agreement were ±6.1, ±4.0 and ±1.4, for GS, RHI and NI, respectively. Mayo endoscopic subgrade and UC clinical score did not show association with any histological scores. Despite clinical and endoscopic remission 7–35% of the patients displayed histological inflammation on a level classified as active disease, depending on the index and cut-off. Conclusion A substantial amount of UC patients in clinical and endoscopic remission display inflammation on a histological level, but the ability to classify these patients accurately and consistently could be improved.
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Battat R, Hemperly A, Truong S, Whitmire N, Boland BS, Dulai PS, Holmer AK, Nguyen NH, Singh S, Vande Casteele N, Sandborn WJ. Baseline Clearance of Infliximab Is Associated With Requirement for Colectomy in Patients With Acute Severe Ulcerative Colitis. Clin Gastroenterol Hepatol 2021; 19:511-518.e6. [PMID: 32348905 PMCID: PMC7606215 DOI: 10.1016/j.cgh.2020.03.072] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 03/06/2020] [Accepted: 03/27/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Hospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated with important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated the baseline infliximab clearance before infliximab salvage therapy and the requirement for colectomy in patients hospitalized for ASUC. METHODS We obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated the baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy. RESULTS In 39 patients with ASUC, the median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/d; P = .005). An infliximab clearance threshold of 0.627 L/d identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627 L/d or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P = .001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. The infliximab dose in the hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 year. CONCLUSIONS In patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC to allow comparative trials on clearance-based vs standard dosing.
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Affiliation(s)
- Robert Battat
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California; Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York
| | - Amy Hemperly
- Division of Gastroenterology, Department of Pediatrics, Rady Children's Hospital University of California, San Diego, La Jolla, California
| | - Stephanie Truong
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - Natalie Whitmire
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - Brigid S Boland
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - Parambir S Dulai
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - Ariela K Holmer
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - Nghia H Nguyen
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - Niels Vande Casteele
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - William J Sandborn
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California.
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Kita T, Ashizuka S, Ohmiya N, Yamamoto T, Kanai T, Motoya S, Hirai F, Nakase H, Moriyama T, Nakamura M, Suzuki Y, Kanmura S, Kobayashi T, Ohi H, Nozaki R, Mitsuyama K, Yamamoto S, Inatsu H, Watanabe K, Hibi T, Kitamura K. Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial. J Gastroenterol 2021; 56:147-157. [PMID: 33140199 PMCID: PMC7862507 DOI: 10.1007/s00535-020-01741-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/18/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Adrenomedullin (AM) is a bioactive peptide having many pleiotropic effects, including mucosal healing and immunomodulation. AM has shown beneficial effects in rodent models and in preliminary study for patients with ulcerative colitis (UC). We performed a clinical trial to investigate the efficacy and safety of AM in patients with UC. METHODS This was a multi-center, double-blind, placebo-controlled phase-2a trial evaluating 28 patients in Japan with steroid-resistant UC. Patients were randomly assigned to four groups and given an infusion of 5, 10, 15 ng/kg/min of AM or placebo for 8 h per day for 14 days. The primary endpoint was the change in Mayo scores at 2 weeks. Main secondary endpoints included the change in Mayo scores and the rate of clinical remission at 8 weeks, defined as a Mayo score 0. RESULTS No differences in the primary or secondary endpoints were observed among the four groups at 2 weeks. Despite the insufficient tracking rate, the Mayo score at 8 weeks was only significantly decreased in the high-dose AM group (15 ng/kg/min) compared with the placebo group (- 9.3 ± 1.2 vs. - 3.0 ± 2.8, P = 0.035), with its rate of clinical remission at 8 weeks being significantly higher (3/3, 100% vs. 0/2, 0%, P = 0.025). We noted mild but no serious adverse events caused by the vasodilatory effect of AM. CONCLUSIONS In this double-blind randomized trial, we observed the complete remission at 8 weeks in patients with steroid-resistant UC receiving a high dose of AM. CLINICAL TRIAL REGISTRY JAPIC clinical trials information; Japic CTI-205255 (200410115290). https://www.clinicaltrials.jp/cti-user/trial/Search.jsp .
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Affiliation(s)
- Toshihiro Kita
- Division of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Miyazaki, Miyazaki, 889-1692, Japan.
| | - Sinya Ashizuka
- Division of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Miyazaki, Miyazaki, 889-1692, Japan
| | - Naoki Ohmiya
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan
| | | | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Satoshi Motoya
- IBD Center, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tomohiko Moriyama
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yasuo Suzuki
- Department of Gastroenterology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan
| | - Shuji Kanmura
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Hidehisa Ohi
- Department of Gastroenterology, Idzuro Imamura Hospital, Kagoshima, Japan
| | | | - Keiichi Mitsuyama
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Shojiro Yamamoto
- Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Haruhiko Inatsu
- Division of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Miyazaki, Miyazaki, 889-1692, Japan
| | - Koji Watanabe
- Division of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Miyazaki, Miyazaki, 889-1692, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Kazuo Kitamura
- Division of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Miyazaki, Miyazaki, 889-1692, Japan
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