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Yzet C, Moreau C, Chatelain D, Meudjo E, Brazier F, Hautefeuille V, Robert C, Decrombecque C, Sarba R, Pichois R, Michaud A, Fumery M. Rectal and Rectosigmoid Endoscopy to Assess Endoscopic and Histological Remission in Ulcerative Colitis: A Prospective Study. Inflamm Bowel Dis 2025:izaf094. [PMID: 40411471 DOI: 10.1093/ibd/izaf094] [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: 12/02/2024] [Indexed: 05/26/2025]
Abstract
BACKGROUND AND AIMS Despite increasing interest in endoscopic and histological remission as a treatment target in ulcerative colitis (UC), the accuracy of endoscopic and histological findings in the left colon and/or rectum to detect pancolonic remission is poorly known. We aimed to compare the diagnostic accuracy of rectosigmoidoscopy (RS) and rectoscopy for detecting endoscopic and histological healing elsewhere in the colon. METHODS Consecutive UC patients who underwent colonoscopy were prospectively included. Endoscopic healing was defined by a Mayo endoscopic score (MES) = 0 on all explored segments and histological healing was defined by a Nancy index ≤ 1 (2 biopsies/segments). The agreement between colonoscopy, RS, and rectoscopy for endoscopic and histological healing was assessed using Cohen's kappa coefficient. RESULTS Eighty patients were included. Thirty-four had an MES = 0 by RS and colonoscopy. The agreement between colonoscopy and RS was almost perfect, with a к index of 0.95 (%-agree 97.5) for Mayo 0, and к of 0.95 for Mayo 0-1 (%-agree 97.5, P < .0001). The agreement between RS and colonoscopy was also almost perfect (к = 0.877, (%-agree 91.7, P < .001) for the assessment of histological healing. The agreement between rectoscopy and colonoscopy for the evaluation of endoscopic (Mayo 0) and histological healing was almost perfect as well (к = 0.83 (%-agree 91.2, P < .001) and к = 0.80 (%-agree 91.7, P < .001)). CONCLUSION For UC patients undergoing treat-to-target interventions, endoscopic and histological findings in the rectum alone provide good accuracy for determining pancolonic endoscopic and histological remission. Rectal examination could be an alternative to RS for monitoring UC patients.
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Affiliation(s)
- Clara Yzet
- Gastroenterology Unit, Amiens University Hospital, Amiens, France
| | - Capucine Moreau
- Gastroenterology Unit, Amiens University Hospital, Amiens, France
| | | | - Erica Meudjo
- Gastroenterology Unit, Amiens University Hospital, Amiens, France
| | - Franck Brazier
- Gastroenterology Unit, Amiens University Hospital, Amiens, France
| | | | - Camille Robert
- Gastroenterology Unit, Amiens University Hospital, Amiens, France
| | | | - Ruxandra Sarba
- Gastroenterology Unit, Amiens University Hospital, Amiens, France
| | | | - Audrey Michaud
- Department of Biostatistics, Amiens University Hospital, Amiens, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Hospital, Amiens, France
- PériTOX - UMR-I INERIS 01, Université de Picardie Jules Verne, Amiens, France
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Reenaers C, Enea D, Nachury M, Laharie D, Bouhnik Y, Fumery M, Gornet JM, Amiot A, Altwegg R, de Vos M, Marteau P, Bourreille A, Nancey S, Viennot S, Louis E, Svrcek M. Impact of Histological Remission for Predicting Clinical Relapse in Crohn's Disease: A Post Hoc Analysis of the Prospective STORI Cohort. J Crohns Colitis 2025; 19:jjae167. [PMID: 39487737 DOI: 10.1093/ecco-jcc/jjae167] [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: 06/15/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND AND AIMS Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is the goal in managing Crohn's disease (CD). The role of histological remission (HR) remains unclear. This study aimed to examine the impact of histological inflammation on clinical relapse risk in CD and explore the relationship between histology, endoscopic scores, and biomarkers. METHODS Patients from the prospective STORI (Stable Remission on Combined Therapy with Immunosuppressors) cohort underwent ileocolonoscopy with Crohn's Disease Endoscopic Index of Severity calculation and 2 biopsies from the most inflamed or previously inflamed areas. Histological scores (Robarts, Geboes, modified Geboes, Nancy, and IBD-DCA) were determined by 2 independent pathologists in a central reading process. Histological remission was defined by specific score thresholds. Clinical relapse, defined by Crohn's Disease Activity Index (CDAI) > 250 or a CDAI increase of 70 points over 2 weeks, was monitored for at least 1 year. RESULTS Out of 115 patients included in STORI, 160 biopsies (44 ileal and 116 colonic) from 76 patients were analyzed. Histological remission rates were 46% (Nancy), 55% (Robarts), 61% (Geboes), and 41% (IBD-DCA). During follow-up, 35 patients (46%) experienced a clinical relapse: 37% with HR and 56% without, based on the Nancy score. Among the mucosal healing subgroup (45 patients), 34% with HR, and 44% without relapsed (p = 0.18). Histological scores did not predict clinical relapse. Only fecal calprotectin was a significant predictor in multivariate analysis (p = 0.029). CONCLUSIONS Despite correlations with endoscopy and biomarkers, histological scores did not predict clinical relapse in CD patients in remission. Thus, these scores are not recommended for clinical practice to assess relapse risk in CD.
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Affiliation(s)
| | - Diana Enea
- Department of Pathology, Hospital Saint-Antoine, Paris, France
| | - Marie Nachury
- Department of Gastroenterology, CHU Lille, Lille, France
| | - David Laharie
- Department of Gastroenterology, CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | | | | | - Jean-Marc Gornet
- Department of Gastroenterology, Hospital Saint-Louis, Paris, France
| | - Aurélien Amiot
- Department of Gastroenterology, Kremelin-Bicètre, Paris, France
| | - Romain Altwegg
- Department of Gastroenterology, CHU Montpellier, Montpellier, France
| | - Martine de Vos
- Department of Gastroenterology, UZ Ghent, Ghent, Belgium
| | | | | | - Stéphane Nancey
- Department of Gastroenterology, Hôpital Lyon-Sud, CHU Lyon, Pierre-Bénite, France
- INSERM U1111, CIRI, Lyon, France
| | | | - Edouard Louis
- Department of Gastroenterology, CHU Liège-Sart Tilman, Liège, Belgium
| | - Magali Svrcek
- Department of Pathology, Hospital Saint-Antoine, Paris, France
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Singh A, Bhardwaj A, Sharma R, Kahlon BK, Dhaliwal AS, Singh D, Kaur S, Jain D, Bansal N, Mahajan R, Kaur K, Singh A, Narang V, Kaur H, Midha V, Sood A. Predictive accuracy of fecal calprotectin for histologic remission in ulcerative colitis. Intest Res 2025; 23:144-156. [PMID: 39523709 PMCID: PMC12081075 DOI: 10.5217/ir.2024.00068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/23/2024] [Accepted: 07/29/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND/AIMS Accurate assessment of disease activity is crucial for effective management and treatment of ulcerative colitis (UC). This study evaluated the correlation between clinical, endoscopic, and histologic measures of disease activity in UC. METHODS Clinical, biochemical, endoscopic, and histologic disease activity was studied in 347 patients with UC. Agreements among various histologic classification systems, namely the Geboes Score (GS), Continuous GS, Nancy Index (NI), and Robarts Histopathology Index (RHI), were analyzed. The predictive accuracy of fecal calprotectin (FC) for endoscopic and histologic remission was assessed. RESULTS We demonstrate a fair to moderate correlation between clinical, endoscopic, and histologic measures of disease activity in UC. There was a robust concordance among GS, Continuous GS, NI, and RHI in distinguishing between patients in histologic remission or activity. The NI detected 75% of patients who met the remission criteria according to the RHI, whereas the RHI identified all patients in remission as defined by the NI. FC levels below 150 μg/g had >70% accuracy in predicting endoscopic remission. FC levels below 150 μg/g showed ≥80% accuracy, and FC levels below 100 μg/g demonstrated ≥ 85% accuracy in predicting histologic remission, regardless of the scoring index applied. Elevated FC levels were associated with both acute and chronic inflammatory infiltrates in biopsy samples. CONCLUSIONS FC is a reliable predictor of histologic remission, with higher accuracy at lower thresholds. The GS, Continuous GS, NI, and RHI demonstrate comparable performance. FC could help stratify patients' need for colonoscopy for the assessment of endoscopic and histologic remission.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Arshia Bhardwaj
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Riya Sharma
- Digestive Diseases Care Foundation, Ludhiana, India
| | - Bhavjeet Kaur Kahlon
- Elson S. Floyd College of Medicine, Washington State University, Everett, WA, USA
| | - Ashvin Singh Dhaliwal
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Dharmatma Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | | | - Devanshi Jain
- Research and Development Centre, Dayanand Medical College and Hospital, Ludhiana, India
| | - Namita Bansal
- Research and Development Centre, Dayanand Medical College and Hospital, Ludhiana, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Aminder Singh
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vikram Narang
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Harpreet Kaur
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
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George AT, Rubin DT. Artificial Intelligence in Inflammatory Bowel Disease. Gastrointest Endosc Clin N Am 2025; 35:367-387. [PMID: 40021234 DOI: 10.1016/j.giec.2024.10.004] [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] [Indexed: 03/03/2025]
Abstract
Artificial intelligence (AI) is being increasingly studied and implemented in gastroenterology. In inflammatory bowel disease (IBD), numerous AI models are being developed to assist with IBD diagnosis, standardization of endoscopic and radiologic disease activity, and predicting outcomes. Further prospective, multicenter studies representing diverse populations and novel applications are needed prior to routine implementation in clinical practice and expected improved outcomes for clinicians and patients.
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Affiliation(s)
- Alvin T George
- Department of Medicine, The University of Chicago, Chicago, IL, USA
| | - David T Rubin
- Department of Medicine, Inflammatory Bowel Disease Center, The University of Chicago, Chicago, IL, USA.
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Ahmed NS, Ma C. IL23p19 therapies for moderately-to-severely active ulcerative colitis. Expert Opin Biol Ther 2025; 25:363-378. [PMID: 40082083 DOI: 10.1080/14712598.2025.2480258] [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: 12/08/2024] [Revised: 03/10/2025] [Accepted: 03/12/2025] [Indexed: 03/16/2025]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory bowel disease. Monoclonal antibodies targeting interleukin (IL)-23p19 have been developed to treat chronic inflammatory diseases mediated by aberrant IL23/Th17 responses, including psoriasis, psoriatic arthritis, and Crohn's disease. More recently, these agents have been evaluated for the treatment of moderately-to-severely active UC. AREAS COVERED In this review, we summarize and discuss phase 2 and pivotal phase 3 clinical trials informing the efficacy and safety of mirikizumab (AMAC, LUCENT, and SHINE), risankizumab (INSPIRE, COMMAND), and guselkumab (QUASAR, VEGA). The literature search included original research publications, secondary publications, and preliminary data from conference abstracts presented at international gastroenterology meetings from the past 5 years. EXPERT OPINION The approval of IL23p19 antagonists expands the armamentarium of effective and safe therapies for patients living with moderately-to-severely active UC. These agents demonstrate potent efficacy for both inducing and maintaining symptomatic and objective disease endpoints, including endoscopic, histologic, and biomarker remission. These well-tolerated agents are effective in both advanced treatment-naïve and experienced patients. Accordingly, IL23p19 antagonists have the potential to be used in a diverse population of patients with UC, and as potential platform therapies for future combinations with other targeted immunomodulatory agents.
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Affiliation(s)
| | - Christopher Ma
- Division of Gastroenterology & Hepatology, University of Calgary, Calgary, AB, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada
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Shehab M, Alrashed F, Alsayegh A, Aldallal U, Ma C, Narula N, Jairath V, Singh S, Bessissow T. Comparative Efficacy of Biologics and Small Molecule in Ulcerative Colitis: A Systematic Review and Network Meta-analysis. Clin Gastroenterol Hepatol 2025; 23:250-262. [PMID: 39182898 DOI: 10.1016/j.cgh.2024.07.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND & AIMS Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but the lack of comparative efficacy trials makes treatment choices a clinical challenge. This network-meta-analysis aimed to compare the relative efficacy of biologics and small molecules in achieving remission in patients with moderate to severe UC. METHODS The literature was searched up to May 2024. Phase 3 placebo or active comparator randomized controlled trials were included. The primary outcome was induction and maintenance of endoscopic improvement (Mayo Endoscopic Score [MES] ≤1). Secondary outcomes were the induction and maintenance of clinical remission, endoscopic (MES = 0) and histological remission. A sub-analysis was performed based on the randomized controlled trial design and previous exposure to biologic therapy. RESULTS We identified 36 studies that met our inclusion criteria, with 14,270 patients with UC. Upadacitinib ranked highest in inducing clinical remission (99.6%), and endoscopic improvement (99.2%), followed by risankizumab (91.4%) and (82.3%), respectively. In maintenance of endoscopic improvement, upadacitinib ranked first (98.6%) followed by filgotinib 200 mg (79.2%). Risankizumab ranked first in the induction of histological remission (89.4%), followed by guselkumab (88.3%). Upadacitinib ranked first (93.1%) in maintaining histological remission, followed by guselkumab (89.5%). CONCLUSION Upadacitinib appears to be superior to other therapies in achieving clinical remission, endoscopic improvement and remission, and histological remission. Furthermore, novel biologics such as risankizumab and guselkumab ranked high in achieving these outcomes. This study highlights the efficacy of small molecule drugs and novel selective interleukin-23s as alternatives to other biologics.
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Affiliation(s)
- Mohammad Shehab
- Division of Gastroenterology, Department of Internal Medicine, Mubarak Alkabeer University Hospital, Kuwait; Department of Pharmacy Practice, Faculty of Pharmacy, Kuwait University, Jabriya, Kuwait.
| | - Fatema Alrashed
- Department of Pharmacy Practice, Faculty of Pharmacy, Kuwait University, Jabriya, Kuwait
| | - Abdulwahab Alsayegh
- Department of medicine, School of Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain, Kingdom of Bahrain
| | - Usama Aldallal
- Department of medicine, School of Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain, Kingdom of Bahrain
| | - Christopher Ma
- Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Neeraj Narula
- Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada
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Chaemsupaphan T, Arzivian A, Leong RW. Comprehensive care of ulcerative colitis: new treatment strategies. Expert Rev Gastroenterol Hepatol 2025. [PMID: 39865726 DOI: 10.1080/17474124.2025.2457451] [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: 10/23/2024] [Revised: 01/16/2025] [Accepted: 01/20/2025] [Indexed: 01/28/2025]
Abstract
INTRODUCTION Ulcerative colitis is a chronic inflammatory condition of the colon driven by aberrant immune activation. Although advanced medical therapies form the cornerstone of ulcerative colitis management, unmet needs include failure to induce and sustain remission in a substantial proportion of patients and in managing acute severe ulcerative colitis. We review new treatment strategies that might improve patient outcomes in the management of moderate-to-severe ulcerative colitis. AREAS COVERED A literature search was conducted using the PubMed database, including studies published from inception to October 2024, selected for their relevance. Recognizing current limitations, this article reviews strategies to improve treatment outcomes in ulcerative colitis using advanced therapies. These approaches include early treatment initiation, dose optimization, positioning newer agents as first-line therapies, combination therapy, targeting novel therapeutic endpoints, and the management of acute severe ulcerative colitis. EXPERT OPINION The strategies discussed may contribute to establishing new standards of care aimed at achieving long-term remission and enhancing patient outcomes. Personalized therapy, which tailors treatment based on individual disease characteristics and risk factors, is anticipated to become a critical aspect of delivering more effective care in the future.
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Affiliation(s)
- Thanaboon Chaemsupaphan
- Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol University, Thailand
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
| | - Arteen Arzivian
- Department of Gastroenterology and Hepatology, St Vincent's Hospital, Sydney, Australia
| | - Rupert W Leong
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
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Akyüz F, An YK, Begun J, Aniwan S, Bui HH, Chan W, Choi CH, Chopdat N, Connor SJ, Desai D, Flanagan E, Kobayashi T, Lai AYH, Leong RW, Leow AHR, Leung WK, Limsrivilai J, Muzellina VN, Peddi K, Ran Z, Wei SC, Sollano J, Teo MMH, Wu K, Ye BD, Ooi CJ. Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition. Intest Res 2025; 23:37-55. [PMID: 39492666 PMCID: PMC11834365 DOI: 10.5217/ir.2024.00089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/08/2024] [Accepted: 08/09/2024] [Indexed: 11/05/2024] Open
Abstract
The lack of clear definition and classification for "moderate ulcerative colitis (UC)" creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.
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Affiliation(s)
- Filiz Akyüz
- Department of Gastroenterology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Yoon Kyo An
- Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Australia
| | - Jakob Begun
- Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Australia
| | - Satimai Aniwan
- Division of Gastroenterology, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Huu Hoang Bui
- Department of Gastroenterology, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Webber Chan
- The Gastroenterology Group, Gleneagles Hospital, Singapore
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Nazeer Chopdat
- Department of Gastroenterology, Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa
| | - Susan J Connor
- Department of Gastroenterology, Liverpool Hospital, Sydney, Australia
- South Western Clinical School, University of New South Wales, Sydney, Australia
| | - Devendra Desai
- Division of Medical Gastroenterology, P. D. Hinduja Hospital, Mumbai, India
| | - Emma Flanagan
- Department of Gastroenterology, St. Vincent’s Hospital, Melbourne, Australia
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Allen Yu-Hung Lai
- Global Health Program, College of Public Health, National Taiwan University, Taipei, Taiwan
- Ferring Pharmaceuticals, Singapore
| | - Rupert W Leong
- Department of Gastroenterology, Concord Hospital, Sydney, Australia
| | | | - Wai Keung Leung
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - Julajak Limsrivilai
- Deparment of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Virly Nanda Muzellina
- Gastrointestinal Endoscopy Center, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
- Universitas Indonesia, Jakarta, Indonesia
| | - Kiran Peddi
- Department of Gastroenterology, Yashoda Hospital, Hyderabad, India
| | - Zhihua Ran
- Department of Gastroenterology, Zhoupu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jose Sollano
- Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines
| | | | - Kaichun Wu
- Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Rubio CA, Lang‐Schwarz C, Vieth M. Architectural crypt distortions in ulcerative colitis: Time for reappraisal. J Gastroenterol Hepatol 2024; 39:2479-2486. [PMID: 39522510 PMCID: PMC11660196 DOI: 10.1111/jgh.16811] [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: 07/27/2024] [Revised: 10/22/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024]
Abstract
Chronic mucosal inflammation and architectural crypt distortions (ACD) are essential for the histologic diagnosis of ulcerative colitis (UC). ACD in UC has been defined as irregularly arranged, dilated, branched, and shortened crypts with inequality of inter-crypt distance. However, neither the diagnostic sections' crypt phenotype nor the cutting mode have been considered. In this regard, previous studies showed that most diagnostic biopsies in UC are fortuitously crosscut at laboratories. In this communication, we review the crypt phenotypes that are included in the ACD in UC notion: crypts in asymmetric branching, crypt rings in tandem, crypts with lateral buds, face-to-face "kissing crypts," crypts-in-crypts, laterally orientated crypts in anthemia fold domains, and crypts with irregular shape and size in innominate groves domains. The awareness that disparate crypt phenotypes may participate in the ACD notion may open new vistas in the interpretation of crypt distortions in crosscut diagnostic sections in UC. The present findings will permit endoscopists and clinicians to better understand the narrative of ACD in the pathological diagnosis.
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Affiliation(s)
- Carlos A Rubio
- Department of Oncology and PathologyKarolinska Institute and University HospitalStockholmSweden
| | - Corinna Lang‐Schwarz
- Institute of PathologyFriedrich‐Alexander‐Universität Erlangen‐Nürnberg, Klinikum BayreuthBayreuthGermany
| | - Michael Vieth
- Institute of PathologyFriedrich‐Alexander‐Universität Erlangen‐Nürnberg, Klinikum BayreuthBayreuthGermany
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Peyrin‐Biroulet L, Adsul S, Stancati A, Dehmeshki J, Kubassova O. An artificial intelligence-driven scoring system to measure histological disease activity in ulcerative colitis. United European Gastroenterol J 2024; 12:1028-1033. [PMID: 38590110 PMCID: PMC11485311 DOI: 10.1002/ueg2.12562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 03/08/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND AND AIMS Assessment and scoring of histological images in Ulcerative colitis (UC) is prone to inter- and intra-observer variability. This study aimed to investigate whether an artificial intelligence (AI) system developed using image processing and machine learning algorithms could measure histological disease activity based on the Nancy index. METHODS A total of 200 histological images of patients with UC were used in this study. A novel AI algorithm was developed using state-of-the-art image processing and machine learning algorithms based on deep learning and feature extraction. The cell regions of each image, followed by the Nancy index, were manually annotated and measured independently by four histopathologists. Manual and AI-automated measurements of the Nancy index score were conducted and assessed using the intraclass correlation coefficient (ICC). RESULTS The 200-image dataset was divided into two groups (80% was used for training and 20% for testing). Intraclass correlation coefficient statistical analyses were performed to evaluate the AI tool and used as a reference to calculate the accuracy. The average ICC among the histopathologists was 89.3 and the average ICC between histopathologists and the AI tool was 87.2. The AI tool was found to be highly correlated with histopathologists. CONCLUSIONS The high correlation of performance of the AI method suggests promising potential for inflammatory bowel disease clinical applications. A standardized automated histological AI-driven scoring system can potentially be used in daily inflammatory bowel disease practice to reduce training needs and resource use, eliminate the subjectivity of the pathologists, and assess disease severity for treatment decisions.
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Affiliation(s)
- Laurent Peyrin‐Biroulet
- Department of GastroenterologyINFINY InstituteFHU‐CUREINSERM NGERENancy University HospitalVandoeuvre‐lès‐NancyFrance
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Horiuchi K, Higashiyama M, Tahara H, Yoshidome Y, Ayaki K, Nishimura H, Tomioka A, Narimatsu K, Komoto S, Tomita K, Hokari R. Absence of Paneth Cell Metaplasia to Predict Clinical Relapse in Ulcerative Colitis with Endoscopically Quiescent Mucosa. Dig Dis Sci 2024; 69:3932-3941. [PMID: 39110367 DOI: 10.1007/s10620-024-08581-9] [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: 03/26/2024] [Accepted: 07/30/2024] [Indexed: 10/20/2024]
Abstract
BACKGROUND Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP). METHODS Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) ≦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score ≧3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated. RESULTS Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15-17.7]; p = 0.03). CONCLUSION The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing.
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Affiliation(s)
- Kazuki Horiuchi
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
| | - Masaaki Higashiyama
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Hiroyuki Tahara
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Yuta Yoshidome
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Kana Ayaki
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Hiroyuki Nishimura
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Akira Tomioka
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Kazuyuki Narimatsu
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Shunsuke Komoto
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Kengo Tomita
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Ryota Hokari
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
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12
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Akiyama S, Miyatani Y, Rubin DT. The evolving understanding of histology as an endpoint in ulcerative colitis. Intest Res 2024; 22:389-396. [PMID: 38475998 PMCID: PMC11534446 DOI: 10.5217/ir.2023.00120] [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: 09/13/2023] [Revised: 01/09/2024] [Accepted: 01/24/2023] [Indexed: 03/14/2024] Open
Abstract
A therapeutic goal for patients with ulcerative colitis (UC) is deep remission including clinical remission and mucosal healing. Mucosal healing was previously defined by endoscopic appearance, but recent studies demonstrate that histological improvements can minimize the risks of experiencing clinical relapse after achieving endoscopic remission, and there is growing interest in the value and feasibility of histological targets of treatment in inflammatory bowel disease, and specifically UC. In this review article, we identify remaining challenges and discuss an evolving role of histology in the management of UC.
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Affiliation(s)
- Shintaro Akiyama
- Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, IL, USA
| | - Yusuke Miyatani
- Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, IL, USA
| | - David T. Rubin
- Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, IL, USA
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13
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Feakins RM. Inflammatory disorders of the large intestine. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:709-857. [DOI: 10.1002/9781119423195.ch35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Herrlinger KR, Stange EF. To STRIDE or not to STRIDE: a critique of "treat to target" in ulcerative colitis. Expert Rev Gastroenterol Hepatol 2024; 18:493-504. [PMID: 39193775 DOI: 10.1080/17474124.2024.2397654] [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: 07/03/2024] [Accepted: 08/24/2024] [Indexed: 08/29/2024]
Abstract
INTRODUCTION The STRIDE consensus intends to complement the clinical endpoint with an endoscopic endpoint of mucosal healing and others as treatment targets in ulcerative colitis. If these targets are not reached, STRIDE requires dose or timing adjustments or switching the medication. This narrative review provides a critique of this concept. AREAS COVERED We analyze and discuss the limitations of current endpoints as targets, their currently limited achievability, and the lacking evidence from controlled trials relating to 'treat to target.' The relevant publications in PubMed were identified in a literature review with the key word 'ulcerative colitis.' EXPERT OPINION In ulcerative colitis, the standard clinical target is measured traditionally by the MAYO-score, but in variable combinations of patient and physician reported outcomes as well as also different definitions of the endoscopic part. Only a score of 0 is more stringent than clinical remission but is only achieved by a minority of patients in first and even less in second line therapy. The concept is not based on clear evidence that patients indeed benefit from appropriate escalation of treatment. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant.
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Affiliation(s)
| | - Eduard F Stange
- Innere Medizin I, UniversitätsklinikTübingen, Tübingen, Germany
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15
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van Gennep S, Fung ICN, de Jong DC, Ramkisoen RK, Clasquin E, de Jong J, de Vries LCS, de Jonge WJ, Gecse KB, Löwenberg M, Woolcott JC, Mookhoek A, D’Haens GR. Histological Outcomes and JAK-STAT Signalling in Ulcerative Colitis Patients Treated with Tofacitinib. J Crohns Colitis 2024; 18:1283-1291. [PMID: 38506097 PMCID: PMC11324337 DOI: 10.1093/ecco-jcc/jjae031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/26/2024] [Indexed: 03/21/2024]
Abstract
BACKGROUND AND AIMS Histological outcomes and JAK-STAT signalling were assessed in a prospective ulcerative colitis [UC] patient cohort after 8 weeks treatment with tofacitinib, an oral Janus kinase [JAK] inhibitor. METHODS Forty UC patients received tofacitinib 10 mg twice daily for 8 weeks. Treatment response was defined as histo-endoscopic mucosal improvement [HEMI]. Histological remission was defined as a Robarts Histopathology Index [RHI] ≤3 points and histological response as 50% decrease in RHI. Mucosal expression of JAK1-3, tyrosine kinase 2 [TYK2], and total signal transducer and activator of transcription [STAT] 1-6 were assessed using immunohistochemistry [IHC]. RESULTS At baseline, the median RHI was 14 (interquartile range [IQR] 10-19). Of 40 [65%] patients, 26 had severe endoscopic disease [endoscopic Mayo score 3] and 31/40 [78%] failed prior anti-tumour necrosis factor [anti-TNF] treatment. At Week 8, 15 patients [38%] had HEMI, 23 patients [58%] histological remission, and 34 [85%] histological response. RHI decreased by a median of 14 points [IQR 9-21] in responders [p <0.001] and by 6 points [IQR 0-13] in non-responders [p = 0.002]. STAT1, STAT3, and STAT5 expression levels decreased significantly in the whole cohort. Responders had lower Week 8 STAT1 expression levels compared with non-responders [0.2%, IQR 0.1-2.8 vs 4.3%, IQR 1.2-11.9, p = 0.001], suggesting more profound STAT1 blockade. A trend of higher baseline JAK2 expression was observed in tofacitinib non-responders [2.7%, IQR 0.1-7.7] compared with responders [0.4%, IQR 0.1-2.1]. CONCLUSIONS Tofacitinib treatment resulted in histological improvement in the majority of UC patients and in a substantial decrease of STAT1, STAT3, and STAT5 expression. HEMI was associated with more profound suppression of STAT1.
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Affiliation(s)
- Sara van Gennep
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Ivan C N Fung
- Amsterdam UMC, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
| | - Djuna C de Jong
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Rishand K Ramkisoen
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Esmé Clasquin
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Jitteke de Jong
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Leonie C S de Vries
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Wouter J de Jonge
- Amsterdam UMC, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
| | - Krisztina B Gecse
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Mark Löwenberg
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | | | - Aart Mookhoek
- University of Bern, Department of Pathology, Institute of Tissue Medicine and Pathology, Bern, Switzerland
| | - Geert R D’Haens
- Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
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16
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Wei ZH, Wu RC, Kuo CJ, Chiu HY, Yeh PJ, Chen CM, Chiu CT, Tsou YK, Chang CW, Pan YB, Le PH. Impact of completely histological remission on reducing flare-ups in moderate-to-severe, biologics-experienced ulcerative colitis patients with endoscopic remission. J Formos Med Assoc 2024:S0929-6646(24)00352-8. [PMID: 39098580 DOI: 10.1016/j.jfma.2024.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024] Open
Abstract
BACKGROUND/PURPOSE Endoscopic remission is presently recognized as the standard therapeutic target in the treatment of ulcerative colitis (UC). However, achieving histological remission is increasingly viewed as a pivotal objective. This study investigates the effects of attaining completely histological remission on the clinical outcomes for UC patients with a high disease burden who have already reached endoscopic remission. This is the inaugural study to concentrate on this specific patient demographic. METHODS This retrospective cohort study enrolled moderate-to-severe, biologics-experienced UC patients with completely endoscopic remission (Mayo endoscopic subscore of 0) between June 2017 and October 2023 at Chang Gung Memorial Hospital, Linkou. Patients were classified into histological remission (HR) and non-histological remission (non-HR) groups based on the Nancy index (NI). HR was defined as an NI score of 0, with all other patients categorized as non-HR. The definition of flare-ups was based on both clinical and endoscopic evidence. Comparative analyses focused on baseline characteristics and clinical outcomes at follow-up. RESULTS A total of 42 patients (HR group: 23, non-HR group: 19) were included. The average follow-up duration was 17.6 months. Baseline characteristics were comparable between the groups. At the end of follow-up, the HR group showed a significantly lower rate of acute flare-ups (26.1% vs. 68.4%, P = 0.006). Although not statistically significant, the HR group also experienced fewer emergency department visits and hospital admissions. CONCLUSIONS For moderate-to-severe, biologics-experienced UC patients in endoscopic remission, achieving completely histological remission is associated with a substantial reduction in flare-ups, suggesting its potential as a valuable therapeutic target.
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Affiliation(s)
- Zih-Hao Wei
- School of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Ren-Chin Wu
- Department of Anatomic Pathology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan
| | - Chia-Jung Kuo
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan
| | - Horng-Yih Chiu
- School of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Pai-Jui Yeh
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan; Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chien-Ming Chen
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Department of Medical Imaging and Interventions, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Cheng-Tang Chiu
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan
| | - Yung-Kuan Tsou
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chen-Wang Chang
- Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Yu-Bin Pan
- Biostatistical Section, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Puo-Hsien Le
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan.
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17
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Schiller B, Wirthgen E, Weber F, Schiller S, Radke M, Claßen M, Däbritz J. Fecal calprotectin and platelet count predict histologic disease activity in pediatric ulcerative colitis: results from a projection-predictive feature selection. Eur J Pediatr 2024; 183:3277-3288. [PMID: 38709314 PMCID: PMC11263432 DOI: 10.1007/s00431-024-05554-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 03/20/2024] [Accepted: 04/03/2024] [Indexed: 05/07/2024]
Abstract
Especially for pediatric patients, proxies of mucosal inflammation are needed. The Pediatric Ulcerative Colitis Activity Index (PUCAI) has been established to predict clinical and endoscopic disease activity. However, histologic inflammation might persist. We applied a special variable selection technique to predict histologic healing in pediatric ulcerative colitis (UC) as parsimoniously (but still as precisely) as possible. The retrospective analysis included data from two study cohorts, comprising 91 visits from 59 pediatric patients with UC. A Bayesian ordinal regression model was used in combination with a projection-predictive feature selection (PPFS) to identify a minimal subset of clinical and laboratory parameters sufficient for the prediction of histologic disease activity. Following the PPFS, CEDATA-GPGE patient registry data were analyzed to investigate the relevance of the selected predictors in relation to PUCAI and Physician Global Assessment (PGA) in up to 6697 patient visits. Fecal calprotectin (FC) and platelet count were identified as the minimal subset of predictors sufficient for prediction of histologic disease activity in pediatric UC. FC and platelet count also appeared to be associated with increasing disease activity as measured by PUCAI and PGA in the CEDATA-GPGE registry. Based on the selected model, predictions can be performed with a Shiny web app. Conclusion: Our statistical approach constitutes a reproducible and objective tool to select a minimal subset of the most informative parameters to predict histologic inflammation in pediatric UC. A Shiny app shows how physicians may predict the histologic activity in a user-friendly way using FC and platelet count. To generalize the findings, further prospective studies will be needed. What is Known: • Histologic healing is a major endpoint in the therapy of ulcerative colitis (UC). • The PUCAI score has been established to predict disease activity in pediatric UC but is not suitable for the prediction of histologic healing. What is New: • Our Bayesian ordinal regression model in combination with a projection-predictive feature selection is a reproducible and objective tool to select the minimal subset of clinical and laboratory parameters to predict histologic inflammation in pediatric UC. • Histologic inflammation in pediatric UC can be non-invasively predicted based on the combination of fecal calprotectin levels and platelet count.
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Affiliation(s)
- B Schiller
- Department of Pediatrics, Rostock University Medical Center, Rostock, Germany
| | - E Wirthgen
- Department of Pediatrics, Rostock University Medical Center, Rostock, Germany
| | - F Weber
- Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany
| | - S Schiller
- Department of Pediatrics, Rostock University Medical Center, Rostock, Germany
- Department of Pediatrics, Greifswald University Medical Center, Greifswald, Germany
| | - M Radke
- Department of Pediatrics, Rostock University Medical Center, Rostock, Germany
| | - M Claßen
- Department of Pediatrics and Adolescent Medicine, Erlangen University Medical Center, Erlangen, Germany
| | - J Däbritz
- Department of Pediatrics, Rostock University Medical Center, Rostock, Germany.
- Department of Pediatrics, Greifswald University Medical Center, Greifswald, Germany.
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D'Amico F, Magro F, Siegmund B, Kobayashi T, Kotze PG, Solitano V, Caron B, Al Awadhi S, Hart A, Jairath V, Dignass A, Peyrin-Biroulet L, Danese S. Disease Clearance as a New Outcome in Ulcerative Colitis: a Systematic Review and Expert Consensus. Inflamm Bowel Dis 2024; 30:1009-1017. [PMID: 37549104 DOI: 10.1093/ibd/izad159] [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: 04/26/2023] [Indexed: 08/09/2023]
Abstract
The concept of disease clearance has been proposed as a potential target in ulcerative colitis (UC). We conducted a systematic review to investigate the role of disease clearance, defined as a composite outcome including simultaneous clinical, endoscopic, and histologic remission of disease in the management of patients with UC. Based on the literature data, statements regarding disease clearance were developed and voted on by the members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) according to a Delphi methodology. A definition of disease clearance was proposed to standardize its use in clinical practice and clinical trials and to provide practical recommendations for its implementation as a therapeutic target in UC.
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Affiliation(s)
- Ferdinando D'Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Fernando Magro
- Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Britta Siegmund
- Medizinische Klinik m. S. Gastroenterologie, Infektiologie und Rheumatologie, Charité, Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Paulo Gustavo Kotze
- Colorectal Surgery Unit, Hospital Universitário Cajuru, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
| | - Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
| | - Benedicte Caron
- University of Lorraine, CHRU-Nancy, Department of Gastroenterology, F-54000 Nancy, France
- University of Lorraine, Inserm, NGERE, F-54000 Nancy, France
| | - Sameer Al Awadhi
- Digestive Diseases Unit, Rashid Hospital, Dubai 003206, United Arab Emirates
| | - Ailsa Hart
- St Mark's Hospital, Harrow, Middlesex, UK
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt am Main, Germany
| | - Laurent Peyrin-Biroulet
- University of Lorraine, CHRU-Nancy, Department of Gastroenterology, F-54000 Nancy, France
- University of Lorraine, Inserm, NGERE, F-54000 Nancy, France
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
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Laterza L, Piscaglia AC, Bibbò S, Arena V, Brisigotti M, Fabbretti G, Stefanelli ML, Cesario V, Maresca R, Poscia A, Pugliese D, Gaetani E, Papa A, Cammarota G, Armuzzi A, Gasbarrini A, Scaldaferri F. Histologic Disease Persists beyond Mucosal Healing and Could Predict Reactivation in Ulcerative Colitis. J Pers Med 2024; 14:505. [PMID: 38793087 PMCID: PMC11122403 DOI: 10.3390/jpm14050505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/01/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
Mucosal healing (MH) is the main target in ulcerative colitis (UC) treatment. Even if MH lowers the risk of disease reactivation, some patients still relapse. Histologic activity (HA) beyond MH could explain these cases. This study aims to assess how many patients with MH have HA and which lesions are associated with relapse. We retrospectively enrolled UC patients showing MH, expressed as a Mayo Endoscopic Subscore (MES) of 0 and 1 upon colonoscopy. We reviewed the histological reports of biopsies evaluating the presence of typical lesions of UC and assessed the number of clinical relapses after 12 months. Among 100 enrolled patients, 2 showed no histological lesions. According to univariate analysis, patients with a higher number of histological lesions at the baseline had a higher risk of relapse (OR 1.25, p = 0.012), as well as patients with basal plasmacytosis (OR 4.33, p = 0.005), lamina propria eosinophils (OR 2.99, p = 0.047), and surface irregularity (OR 4.70, p = 0.010). However, in the multivariate analysis, only basal plasmacytosis (OR 2.98, p = 0.050) and surface irregularity (OR 4.50, p = 0.024) were confirmed as risk factors for disease reactivation. HA persists in a significant percentage of patients with MH. Despite the presence of MH, patients with basal plasmacytosis and surface irregularity have a higher risk of relapse.
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Affiliation(s)
- Lucrezia Laterza
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
| | | | - Stefano Bibbò
- UOC di Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Vincenzo Arena
- Istituto di Anatomia Patologica, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica-Area Anatomia Patologica, Fondazione Policlinico Universitario “A.Gemelli” IRCCS, 00168 Rome, Italy
| | | | | | | | - Valentina Cesario
- Endoscopy and Gastroenterology Unit, State Hospital, 47893 Cailungo, San Marino
| | - Rossella Maresca
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Andrea Poscia
- UOC ISP Prevention and Surveillance of Infectious and Chronic Diseases, Department of Prevention, Local Health Authority (ASUR-AV2), 60035 Jesi, Italy
| | - Daniela Pugliese
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
| | - Eleonora Gaetani
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Alfredo Papa
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Giovanni Cammarota
- UOC di Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | | | - Antonio Gasbarrini
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Franco Scaldaferri
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Shehab M, Al Akram S, Hassan A, Alrashed F, Jairath V, Bessissow T. Histological Disease Activity as Predictor of Clinical Relapse, Hospitalization, and Surgery in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2024; 30:563-572. [PMID: 37541185 DOI: 10.1093/ibd/izad119] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Indexed: 08/06/2023]
Abstract
BACKGROUND The clinical impact of histological remission on short- and long-term clinical outcomes in patients with inflammatory bowel disease (IBD) is not well established. We assessed risk of clinical relapse, hospitalization, and need for surgery in patients achieving histological remission in comparison with active histological disease. METHODS A systematic review was conducted using MEDLINE, Scopus, Cochrane CENTRAL, EMBASE, and conference abstracts from inception to November 2022. Our main outcome was the rate of clinical relapse in patients with IBD who reached histological remission vs patients with active histological disease. Secondary outcomes were clinical complications of IBD such as hospitalization and need for surgery. The endpoints were investigated at 2 time points, 6 to 12 months (short term) and >12 months (long term). RESULTS Short-term outcome analysis showed that the risk of clinical relapse was significantly higher in ulcerative colitis patients with active histological disease in comparison with patients at histological remission (risk ratio [RR], 2.41; 95% confidence interval [CI], 1.69-3.44; P < .01). The risk of hospitalization in ulcerative colitis patients was not significant among the 2 groups (RR, 4.22; 95% CI, 0.91-19.62; P = .07). Long-term outcome analysis demonstrated that the risk of clinical relapse (RR, 2.07; 95% CI, 1.55-2.76; P < .01), need for surgery (RR, 3.14; 95% CI, 1.53-6.45; P < .01), and hospitalization (RR, 2.52; 95% CI, 1.59-4.00; P < .01) was significantly higher in patients with active histological disease. CONCLUSIONS Histological remission in IBD represents an important therapeutic goal that is not yet routinely pursued in clinical practice. In our study, patients who achieved histological remission have more favorable outcomes than those with active histological disease in ulcerative colitis.
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Affiliation(s)
- Mohammad Shehab
- Division of Gastroenterology, Department of Internal Medicine, Mubarak Alkaber Hospital, Kuwait City, Kuwait
| | - Sahad Al Akram
- Division of Gastroenterology, Department of Internal Medicine, Mubarak Alkaber Hospital, Kuwait City, Kuwait
| | - Amro Hassan
- Division of Gastroenterology, Department of Internal Medicine, Mubarak Alkaber Hospital, Kuwait City, Kuwait
| | - Fatema Alrashed
- Department of Pharmacy Practice, Faculty of Pharmacy, Kuwait University, Kuwait City, Kuwait
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, ON, Canada
- Lawson Health Research Institute, Western University, London, ON, Canada
- Department of Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Center, Montreal, QC, Canada
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Molander P, Kosunen M, Eronen H, Tillonen J, Käräjämäki A, Heikkinen M, Punkkinen J, Mattila R, Toppila I, Hölsä O, Kalpala K, Henrohn D, Af Björkesten CG. Tofacitinib real-world experience in ulcerative colitis in Finland (FinTofUC): a retrospective non-interventional multicenter patient chart data study. Scand J Gastroenterol 2024; 59:425-432. [PMID: 38156792 DOI: 10.1080/00365521.2023.2298361] [Citation(s) in RCA: 2] [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: 10/04/2023] [Accepted: 12/17/2023] [Indexed: 01/03/2024]
Abstract
OBJECTIVES The aim was to define the effectiveness of tofacitinib and to characterize the patient population receiving tofacitinib in a real-world cohort clinical setting for ulcerative colitis (UC) in Finland. METHODS This is a retrospective non-interventional multicenter patient chart data study conducted in 23 Finnish Inflammatory Bowel Disease (IBD) centers. Baseline demographic and clinical data, clinical remission, steroid-free remission rate and time to tofacitinib discontinuation, colectomy or UC-related hospitalization were studied. RESULTS The study included 252 UC patients of which 69% were male. Most patients had extensive disease (71%) and were bio-experienced (81%). Tofacitinib demonstrated positive treatment outcomes with clinical response, clinical remission, and steroid-free clinical remission at one year in 33%, 34% and 31% of patients, respectively. Moreover, 64% of patients in pMayo remission at week 16 from the start of tofacitinib were still in remission at one year. Only no or mild disease activity compared to moderate activity at baseline was associated with a higher probability of achieving remission according to pMayo at six months, p = .008. Hospitalizations and/or colectomies during the study period (before treatment discontinuation/end of follow-up) were low (n = 24), with less than 5 colectomies. CONCLUSIONS In this real-world cohort, including a majority of bio-experienced UC patients, tofacitinib was effective in achieving steroid-free clinical remission in a third of the population at one year. A majority of patients in remission at week 16 were also in remission at one year. Results are in line with earlier published real-world studies. Registration: ClinicalTrials.gov NCT05082428.
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Affiliation(s)
- Pauliina Molander
- Abdominal Center, Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | | | - Heli Eronen
- Department of Internal Medicine, Kanta-Häme Central Hospital, Hämeenlinna, Finland
| | - Jyrki Tillonen
- Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
| | - Aki Käräjämäki
- Department of Internal Medicine, Vaasa Central Hospital, Vaasa, Finland
| | - Markku Heikkinen
- Department of Internal Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Jari Punkkinen
- Abdominal Center, Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | | | | | | | | | - Dan Henrohn
- Pfizer AB, Stockholm, Sweden
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Clas-Göran Af Björkesten
- Abdominal Center, Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Mogilevski T, Nguyen AL, Ajamian M, Smith R, Rosella S, Sparrow MP, Moore GT, Gibson PR. Intestinal barrier biomarkers in clinical evaluation of patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2024; 36:271-280. [PMID: 38305113 DOI: 10.1097/meg.0000000000002681] [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] [Indexed: 02/03/2024]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is associated with chronic intestinal barrier dysfunction, though its non-invasive assessment remains challenging. This study aimed to determine how four putative circulating markers vary across differing states of intestinal inflammation and with therapy in patients with IBD. METHODS Plasma samples from one prospective cross-sectional and four longitudinal studies, including healthy controls, were analysed for markers of lipopolysaccharide translocation, lipopolysaccharide-binding protein (LBP) and soluble-CD14 (sCD14), and markers of epithelial injury, syndecan-1 and intestinal-type fatty acid-binding protein (IFABP). Inflammatory activity was determined using objective measures. RESULTS Compared with healthy subjects, concentrations of LBP and sCD14 were higher in patients with active (P < 0.001) and severe ulcerative colitis (UC) (P < 0.0001) and active Crohn's disease (CD) (P < 0.001). In UC in remission, LBP was less than in active disease (P = 0.011) LBP levels decreased longitudinally before and after induction of medical therapy in patients with IBD (P = 0.030) and as severe UC was brought into remission at weeks 2 and 12 (P ≤ 0.022). Response to treatment was associated with higher baseline levels of LBP (P = 0.019) and soluble-CD14 (P = 0.014). Concentrations of syndecan-1 and IFABP were or tended to be lower in UC and CD in active disease and did not change with successful therapy. CONCLUSION While markers of epithelial injury were subnormal with active disease and did not change with therapy, markers of lipopolysaccharide translocation directly reflected intestinal inflammation, reduced with successful therapy and predicted treatment response.
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Affiliation(s)
- Tamara Mogilevski
- Department of Gastroenterology, Central Clinical School, Monash University, and Alfred Health
| | - Anke L Nguyen
- Department of Gastroenterology, Central Clinical School, Monash University, and Alfred Health
- Gastroenterology Department, Monash Health
| | - Mary Ajamian
- Department of Gastroenterology, Central Clinical School, Monash University, and Alfred Health
| | - Rebecca Smith
- Department of Gastroenterology, Central Clinical School, Monash University, and Alfred Health
| | - Sam Rosella
- Department of Gastroenterology, Central Clinical School, Monash University, and Alfred Health
| | - Miles P Sparrow
- Department of Gastroenterology, Central Clinical School, Monash University, and Alfred Health
| | - Gregory T Moore
- Gastroenterology Department, Monash Health
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Central Clinical School, Monash University, and Alfred Health
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Goodsall TM, Day AS, Andrews JM, Ruszkiewicz A, Ma C, Bryant RV. Composite Assessment Using Intestinal Ultrasound and Calprotectin Is Accurate in Predicting Histological Activity in Ulcerative Colitis: A Cohort Study. Inflamm Bowel Dis 2024; 30:190-195. [PMID: 36928672 PMCID: PMC10834160 DOI: 10.1093/ibd/izad043] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Indexed: 03/18/2023]
Abstract
BACKGROUND Beyond endoscopic remission, histological remission in ulcerative colitis (UC) is predictive of clinical outcomes. Intestinal ultrasound (IUS) may offer a noninvasive surrogate marker for histological activity; however, there are limited data correlating validated ultrasound and histological indices. AIM Our aim was to determine the correlation of IUS activity in UC with a validated histological activity index. METHODS Twenty-nine prospective, paired, same-day IUS/endoscopy/histology/fecal calprotectin (FC) cases were included. Intestinal ultrasound activity was determined using the Milan Ultrasound Criteria, histological activity using the Nancy Histological Index, endoscopic activity using Mayo endoscopic subscore and Ulcerative Colitis Endoscopic Index of Severity, and clinical activity using the Simple Clinical Colitis Activity Score. RESULTS Histological activity demonstrated a significant linear association with overall IUS activity (coefficient 0.14; 95% CI, 0.03-0.25; P = .011). Intestinal ultrasound activity was also significantly associated with endoscopic activity (0.32; 95% CI, 0.14-0.49; P < 0.001), total Mayo score (0.31; 95% CI, 0.02-0.60; P = .036) but not FC (0.10; 95% CI, -0.01 to 0.21; P = .064) or clinical disease activity (0.04; 95% CI, -0.21 to 0.28; P = .768). A composite of IUS and FC showed the greatest association (1.31; 95% CI, 0.43-2.18; P = .003) and accurately predicted histological activity in 88% of cases (P = .007), with sensitivity of 88%, specificity 80%, positive predictive value 95%, and negative predictive value 57%. CONCLUSIONS Intestinal ultrasound is an accurate noninvasive marker of histological disease activity in UC, the accuracy of which is further enhanced when used in composite with FC. This can reduce the need for colonoscopy in routine care by supporting accurate point-of-care decision-making in patients with UC.
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Affiliation(s)
- Thomas M Goodsall
- IBD Service, Department of Gastroenterology, John Hunter Hospital, Newcastle, Australia
- Faculty of Health Sciences, School of Medicine, University of Adelaide, Adelaide, Australia
| | - Alice S Day
- Faculty of Health Sciences, School of Medicine, University of Adelaide, Adelaide, Australia
- IBD Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, Australia
| | - Jane M Andrews
- Faculty of Health Sciences, School of Medicine, University of Adelaide, Adelaide, Australia
- IBD Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, Australia
| | | | - Christopher Ma
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Robert V Bryant
- Faculty of Health Sciences, School of Medicine, University of Adelaide, Adelaide, Australia
- IBD Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, Australia
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24
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Pai RK, D'Haens G, Kobayashi T, Sands BE, Travis S, Jairath V, De Hertogh G, Park B, McGinnis K, Redondo I, Lipitz NG, Gibble TH, Magro F. Histologic assessments in ulcerative colitis: the evidence behind a new endpoint in clinical trials. Expert Rev Gastroenterol Hepatol 2024; 18:73-87. [PMID: 38509826 DOI: 10.1080/17474124.2024.2326838] [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: 06/05/2023] [Accepted: 03/01/2024] [Indexed: 03/22/2024]
Abstract
INTRODUCTION Treatment goals for ulcerative colitis (UC) are evolving from the achievement of clinical remission to more rigorous goals defined by endoscopic and histologic healing. Achievement of deeper remission targets aims to reduce the risk of colectomy, hospitalizations, and colorectal cancer. AREAS COVERED This review covers histologic assessments, histologic remission as a clinical trial endpoint, and the association between histologic disease activity and clinical outcomes. Future directions are also discussed, including the use of advanced imaging and artificial intelligence technologies, as well as potential future treatment targets beyond histologic remission. EXPERT OPINION Histologic assessments are used for their sensitivity in measuring mucosal inflammatory changes in UC. Due to correlation with disease activity, histologic assessments may support clinical decision-making regarding treatment decisions as such assessments can be associated with rates of clinical relapse, hospitalization, colectomy, and neoplasia. While histologic remission is limited by varying definitions and multiple histologic indices, work is ongoing to create a consensus on the use of histologic assessments in clinical trials. As research advances, aspirational targets beyond histologic remission, such as molecular healing and disease clearance, are being explored.
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Affiliation(s)
- Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ, USA
| | - Geert D'Haens
- Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, Netherlands
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Simon Travis
- Kennedy Institute and Biomedical Research Centre, University of Oxford, Oxford, UK
| | - Vipul Jairath
- Division of Gastroenterology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Gert De Hertogh
- Department of Pathology, University Hospitals Leuven, Leuven, Belgium
| | - Bomina Park
- Eli Lilly and Company, Indianapolis, IN, USA
| | | | | | | | | | - Fernando Magro
- CINTESIS@RISE, Departmento, Faculty of Medicine of the University of Porto, Porto, Portugal
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25
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Yang L, Yuan L. Identification of novel N7-methylguanine-related gene signatures associated with ulcerative colitis and the association with biological therapy. Inflamm Res 2023; 72:2169-2180. [PMID: 37889323 DOI: 10.1007/s00011-023-01806-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 07/23/2023] [Accepted: 10/11/2023] [Indexed: 10/28/2023] Open
Abstract
OBJECTIVE Ulcerative colitis (UC) is an inflammatory disease characterized by recurrent episodes of chronic intestinal inflammation. It is closely associated with immune dysregulation in the intestines. However, the mechanisms underlying the role of immune-related N7-methylguanosine (m7G) internal modification in UC remain unclear. METHODS We conducted a screening of differentially expressed genes (DEGs) associated with m7G and performed immune infiltration analysis. We then investigated the correlation between m7G-related DEGs and immune cells or pathways. To further explore the functional implications, we conducted functional enrichment analysis to identify gene modules that strongly correlated with hub gene expression. In addition, we constructed a miRNA regulatory network for the hub genes in UC. Furthermore, we examined the association between hub genes and disease remission in UC patients undergoing biologic therapy. RESULTS We obtained 13 m7G-related DEGs and conducted an in-depth analysis of immune infiltration. Among them, we identified five hub genes (NUDT7, NUDT12, POLR2H, QKI, and PRKCB) that showed diagnostic potential for UC. Through WGCNA and KEGG analysis, we found that gene modules strongly correlated with m7G hub gene expression were enriched in inflammation-related pathways. Furthermore, Kaplan-Meier survival analysis revealed a significant association between changes in hub gene expression levels and disease remission in UC patients undergoing biologic therapy. CONCLUSION The findings of this study demonstrate that five m7G-related DEGs, including the m7G-modified recognition protein QKI, play a key role in the occurrence and progression of UC intestinal inflammation, which is closely related to intestinal immunity. These results provide valuable insights into the mechanisms of m7G modification in UC development and offer new perspectives for exploring novel therapeutic targets for UC.
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Affiliation(s)
- Lichao Yang
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Lianwen Yuan
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
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Gao J, Nie R, Chen Y, Yang W, Ren Q. Comparative of the effectiveness and safety of biological agents, small molecule drugs, and microbiome therapies in ulcerative colitis: Systematic review and network meta-analysis. Medicine (Baltimore) 2023; 102:e35689. [PMID: 37904440 PMCID: PMC10615430 DOI: 10.1097/md.0000000000035689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 09/27/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND Biological agents are commonly used for the first-line treatment of ulcerative colitis (UC). However, small-molecule drugs and microbiome therapies are now being used as new treatments for ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics, small-molecule drugs, and microbiome therapies for the treatment of patients with moderate-to-severe ulcerative colitis. METHODS We searched the Cochrane, Embase, and PubMed databases from their inception to December 2022. RCTs that recruited patients with moderate-to-severe ulcerative colitis treated with biological agents, small-molecule drugs, and microbiome therapies. Efficacy outcomes were induction of clinical remission and mucosal healing; safety outcomes were adverse events and serious adverse events. A network meta-analysis with multivariate consistency model random-effect meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety. RESULTS A total of 31 RCTs comprising 7933 UC patients were included in our studies. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib ranked highest for induction of clinical remission (SUCRA, 0.83) and mucosal healing (SUCRA, 0.44). Moreover, no treatments were found to increase the occurrence of adverse events compared with placebos. Ustekinumab ranked lowest for adverse events (SUCRA 0.26) and probiotic ranked lowest for serious adverse events (0·21), whereas tofacitinib ranked highest for adverse events (0·43) and upadacitinib ranked highest for serious adverse events (0·43). CONCLUSION In this systematic review and network meta-analysis, we found upadacitinib to be ranked highest for the induction of clinical remission and mucosal healing, but the worst performing agent in terms of adverse events in UC patients. Probiotics were the best-performing agent for safety outcomes. More trials of direct comparisons are needed to inform clinical decision-making with greater confidence.
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Affiliation(s)
- Jie Gao
- Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Rui Nie
- Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yalan Chen
- Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Wei Yang
- Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Qian Ren
- Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
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Wong R, Qin L, Pan Y, Mahtani P, Longman R, Lukin D, Scherl E, Battat R. Higher Adalimumab Trough Levels Are Associated with Histologic Remission and Mucosal Healing in Inflammatory Bowel Disease. J Clin Med 2023; 12:6796. [PMID: 37959261 PMCID: PMC10647216 DOI: 10.3390/jcm12216796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 10/14/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
(1) Many patients with inflammatory bowel disease (IBD) in endoscopic remission have persistent histologic activity, which is associated with worse outcomes. There are limited data on the association between adalimumab drug concentrations and histologic outcomes using validated histologic indices. We aimed to assess the relationship between adalimumab concentrations and the Robarts Histopathology Index (RHI). (2) Patients from a tertiary IBD center from 2013 to 2020 with serum adalimumab (ADA) trough concentrations measured during maintenance therapy (≥14 weeks) and a colonoscopy or flexible sigmoidoscopy with biopsies performed within 90 days of drug level were included. Blinded histologic scoring using the RHI was performed. Primary analysis assessed the relationship between adalimumab drug concentrations and histologic remission using receiver operating characteristic curve analysis. (3) In 36 patients (26 Crohn's Disease, 9 ulcerative colitis, 1 indeterminate), median adalimumab concentrations were higher (17.3 ug/mL, 12.2-24.0) in patients with histologic remission compared to those without (10.3 ug/mL, 6.8-13.9, p = 0.008). The optimal ADA concentration identified using the Youden threshold was ≥16.3 ug/mL (sensitivity 70%, specificity 90%). Patients with ADA ≥ 16.3 ug/mL had higher histologic remission rates (78%) compared to lower ADA concentrations (14%, p= 0.002), as well as higher mucosal healing rates (86%) compared to lower levels (12%, p = 0.001). Symptoms correlated weakly and non-significantly with both histologic (RHI) scores (r = 0.25, p = 0.2) and adalimumab concentrations (r = 0.05, p = 0.8). (4) The current study demonstrated that higher serum adalimumab concentrations (≥16.3 ug/mL) are needed for histologic remission and mucosal healing assessed using the RHI.
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Affiliation(s)
- Rochelle Wong
- Division of Gastroenterology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Lihui Qin
- Department of Pathology, Weill Cornell Medical College, New York, NY 10065, USA
| | - Yushan Pan
- Division of Gastroenterology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Prerna Mahtani
- Division of Gastroenterology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Randy Longman
- Division of Gastroenterology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Dana Lukin
- Division of Gastroenterology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ellen Scherl
- Division of Gastroenterology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Robert Battat
- Division of Gastroenterology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Division of Gastroenterology, Centre Hospitalier de l’Universite de Montreal, Montreal, QC H2X 0C1, Canada
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Magro F, Pai RK, Kobayashi T, Jairath V, Rieder F, Redondo I, Lissoos T, Morris N, Shan M, Park M, Peyrin-Biroulet L. Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes. J Crohns Colitis 2023; 17:1457-1470. [PMID: 37057827 PMCID: PMC10588772 DOI: 10.1093/ecco-jcc/jjad050] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Indexed: 04/15/2023]
Abstract
BACKGROUND AND AIMS To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC]. METHODS Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N = 1162, induction] and W40 [LUCENT-2: N = 544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with/without HR. RESULTS Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [p <0.001], irrespective of prior biologic/tofacitinib failure [p <0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic/tofacitinib failure were predictors of HEMI at W12 [p <0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [p <0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [p <0.05]; ER at W12 was associated with clinical remission [CR] [p <0.05] and corticosteroid-free remission [CSFR] at W40 [p = 0.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN + HR] at W40 was associated with bowel urgency remission at W40 [p <0.05]. CONCLUSIONS Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086; LUCENT-2, NCT03524092.
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Affiliation(s)
- Fernando Magro
- Department of Gastroenterology, University Hospital São João, Porto, Portugal
- CINTESIS@RISE - Health Research Network, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
- Alimentiv Inc., London, ON, Canada
- Department of Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Florian Rieder
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Isabel Redondo
- Eli Lilly Portugal, Produtos Farmacêuticos Lda., Lisbon, Portugal
| | | | | | | | | | - Laurent Peyrin-Biroulet
- University of Lorraine, Inserm, NGERE, Nancy, and Groupe Hospitalier Privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France
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Parkes G, Ungaro RC, Danese S, Abreu MT, Arenson E, Zhou W, Ilo D, Laroux FS, Deng H, Sanchez Gonzalez Y, Peyrin-Biroulet L. Correlation of mucosal healing endpoints with long-term clinical and patient-reported outcomes in ulcerative colitis. J Gastroenterol 2023; 58:990-1002. [PMID: 37490069 PMCID: PMC10522527 DOI: 10.1007/s00535-023-02013-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 06/20/2023] [Indexed: 07/26/2023]
Abstract
BACKGROUND We evaluated the clinical relevance of achieving histologic endoscopic mucosal improvement (HEMI) and the more stringent target of histologic endoscopic mucosal remission (HEMR) in the phase 3 maintenance trial of upadacitinib for moderately to severely active ulcerative colitis. METHODS Clinical and patient-reported outcomes were assessed in patients with clinical response after 8- or 16-week upadacitinib induction who received 52-week upadacitinib maintenance treatment. Cross-sectional and predictive analyses evaluated the relationship between HEMR or HEMI at Week 8/16 and Week 52, respectively, and outcomes at Week 52. Adjusted odds ratios (aOR) were derived from logistic regressions for patients achieving HEMR or HEMI without HEMR versus those not achieving HEMI. RESULTS Cross-sectional analyses showed that patients with HEMR had greater odds of achieving all clinical and patient-reported outcomes at Week 52 than those not achieving HEMI. In predictive analyses, patients with HEMR at Week 8/16 had significantly greater odds of achieving clinical remission (aOR = 3.6, p = 0.001) and endoscopic remission (aOR = 3.9, p < 0.001) at Week 52 than patients not achieving HEMI and HEMR. For patients achieving HEMI without HEMR, these odds were lower: clinical remission (aOR = 3.2, p < 0.001) and endoscopic remission (aOR = 2.4, p = 0.010). The odds of achieving clinically meaningful improvements in most patient-reported outcomes were directionally similar between HEMI and HEMR, but not statistically different to patients not achieving HEMI. No hospitalizations or surgeries were observed in patients with HEMR at Week 52. CONCLUSIONS Achievement of HEMR or HEMI is clinically relevant with HEMR being associated with greater likelihood of improvement in long-term clinical and patient-reported outcomes. https://www. CLINICALTRIALS gov NCT02819635.
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Affiliation(s)
- Gareth Parkes
- Dept of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK.
| | - Ryan C Ungaro
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Maria T Abreu
- Division of Gastroenterology, Crohn's and Colitis Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | | | | | | | | | - Huiwen Deng
- AbbVie Inc., Chicago, IL, USA
- Department of Pharmacy Systems Outcomes and Policy, University of Illinois at Chicago, Chicago, IL, USA
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Faingelernt Y, Morgenstern S, Matar M, Weintraub Y, Shamir R, Shouval DS. Correlation Between the Nancy Histopathology Index and Markers of Disease Activity in Pediatric Ulcerative Colitis. J Pediatr Gastroenterol Nutr 2023; 76:782-785. [PMID: 36821853 DOI: 10.1097/mpg.0000000000003753] [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] [Indexed: 02/25/2023]
Abstract
The Nancy Histological Index (NHI) was developed to assess histological disease activity in adult ulcerative colitis (UC) patients. However, data in pediatrics is limited. Our aim was to determine whether the NHI correlates with different indices of disease activity in pediatric UC patients. We retrospectively reviewed the NHI in rectal biopsies from 61 pediatric UC patients (median age 14.3 years), of whom 34 (55.7%) were newly diagnosed. The median Pediatric Ulcerative Colitis Activity Index (PUCAI) score among participants was 30 (interquartile range 5-55). Most patients exhibited an NHI of 3 (41/61, 67.2%) or 4 (8/61, 13.1%), reflecting moderate-severe histologic inflammation. A moderate positive correlation was identified between the NHI and PUCAI, fecal calprotectin, and Mayo endoscopic scores ( r = 0.60, 0.54, and 0.56 respectively, P ≤ 0.001), but not with CRP or albumin. These results indicate that the NHI has a modest correlation with clinical, laboratory and endoscopic indices of disease activity in pediatric UC patients.
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Affiliation(s)
- Yaniv Faingelernt
- From the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
- the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Sara Morgenstern
- the Institute of Pathology, Rabin Medical Center, Petah Tikva, Israel
- the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Manar Matar
- From the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
- the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Weintraub
- From the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
- the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Raanan Shamir
- From the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
- the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dror S Shouval
- From the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
- the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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31
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Fabian O, Bajer L, Drastich P, Harant K, Sticova E, Daskova N, Modos I, Tichanek F, Cahova M. A Current State of Proteomics in Adult and Pediatric Inflammatory Bowel Diseases: A Systematic Search and Review. Int J Mol Sci 2023; 24:ijms24119386. [PMID: 37298338 DOI: 10.3390/ijms24119386] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/23/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are systemic immune-mediated conditions with predilection for the gastrointestinal tract and include Crohn's disease and ulcerative colitis. Despite the advances in the fields of basic and applied research, the etiopathogenesis remains largely unknown. As a result, only one third of the patients achieve endoscopic remission. A substantial portion of the patients also develop severe clinical complications or neoplasia. The need for novel biomarkers that can enhance diagnostic accuracy, more precisely reflect disease activity, and predict a complicated disease course, thus, remains high. Genomic and transcriptomic studies contributed substantially to our understanding of the immunopathological pathways involved in disease initiation and progression. However, eventual genomic alterations do not necessarily translate into the final clinical picture. Proteomics may represent a missing link between the genome, transcriptome, and phenotypical presentation of the disease. Based on the analysis of a large spectrum of proteins in tissues, it seems to be a promising method for the identification of new biomarkers. This systematic search and review summarize the current state of proteomics in human IBD. It comments on the utility of proteomics in research, describes the basic proteomic techniques, and provides an up-to-date overview of available studies in both adult and pediatric IBD.
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Affiliation(s)
- Ondrej Fabian
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
- Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University and Thomayer Hospital, 140 59 Prague, Czech Republic
| | - Lukas Bajer
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
- Institute of Microbiology, Czech Academy of Sciences, 142 20 Prague, Czech Republic
| | - Pavel Drastich
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
| | - Karel Harant
- Proteomics Core Facility, Faculty of Science, Charles University, 252 50 Vestec, Czech Republic
| | - Eva Sticova
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
- Department of Pathology, Royal Vinohrady Teaching Hospital, Srobarova 1150/50, 100 00 Prague, Czech Republic
| | - Nikola Daskova
- Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
| | - Istvan Modos
- Department of Informatics, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
| | - Filip Tichanek
- Department of Informatics, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
| | - Monika Cahova
- Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
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32
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Crispino F, Michielan A, Grova M, Tieppo C, Mazza M, Rogger TM, Armelao F. Exit strategies in inflammatory bowel disease: Looking beyond anti-tumor necrosis factors. World J Clin Cases 2023; 11:2657-2669. [PMID: 37214561 PMCID: PMC10198103 DOI: 10.12998/wjcc.v11.i12.2657] [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: 01/20/2023] [Revised: 03/10/2023] [Accepted: 03/29/2023] [Indexed: 04/25/2023] Open
Abstract
The long-term management of patients with inflammatory bowel disease (IBD) is still a matter of debate, and no clear guidelines have been issued. In clinical practice, gastroenterologists often have to deal with patients in prolonged remission after immunomodulatory or immunosuppressive therapies. When planning an exit strategy for drug withdrawal, the risk of disease relapse must be balanced against the risk of drug-related adverse events and healthcare costs. Furthermore, there is still a dearth of data on the withdrawal of novel biologics, such as the anti-α4β7 integrin antibody (vedolizumab) and anti-IL12/23 antibody (ustekinumab), as well as the small molecule tofacitinib. Models for estimating the risk of disease relapse and the efficacy of retreatment should be evaluated according to the patient's age and IBD phenotype. These models should guide clinicians in programming a temporary drug withdrawal after discussing realistic outcomes with the patient. This would shift the paradigm from an exit strategy to a holiday strategy.
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Affiliation(s)
- Federica Crispino
- Azienda Provinciale per i Servizi Sanitari, Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento 38122, Italy
| | - Andrea Michielan
- Azienda Provinciale per i Servizi Sanitari, Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento 38122, Italy
| | - Mauro Grova
- Inflammatory Bowel Disease Unit, Department of Medicine, Azienda Ospedaliera Ospedali Riuniti, Villa Sofia-Cervello, Palermo 90146, Italy
| | - Chiara Tieppo
- Azienda Provinciale per i Servizi Sanitari, Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento 38122, Italy
| | - Marta Mazza
- Azienda Provinciale per i Servizi Sanitari, Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento 38122, Italy
| | - Teresa Marzia Rogger
- Azienda Provinciale per i Servizi Sanitari, Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento 38122, Italy
| | - Franco Armelao
- Azienda Provinciale per i Servizi Sanitari, Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento 38122, Italy
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33
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Boulagnon-Rombi C, Marchal A, Lirsac M, Svrcek M. [Inflammatory bowel diseases: Scoring and pathological reports optimization]. Ann Pathol 2023:S0242-6498(23)00083-4. [PMID: 37059601 DOI: 10.1016/j.annpat.2023.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/13/2023] [Accepted: 03/26/2023] [Indexed: 04/16/2023]
Abstract
The two main forms of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). Both diseases have inflammatory flare-ups that alternate with periods of remission. The pathologist may examine biopsies of the digestive tract from IBD patients in different contexts: at the time of the initial diagnosis, in the event of a disease flare-up in order to differentiate a flare of the disease from another cause, particularly an infectious one, and during the long term follow-up of the disease in order to detect the occurrence of dysplastic lesions. Pathologists are increasingly involved in the evaluation of inflammatory activity during the follow-up of IBD patients. The therapeutic management of IBD has evolved significantly and the emergence of new treatments allows a global approach targeting endoscopic mucosal healing. However, mucosal healing is not always correlated with histological healing. Numerous studies have shown the value of histological evaluation during follow-up. A higher score for histological activity in ulcerative colitis predicts a higher likelihood of neoplasia. Histological activity is a better predictor than endoscopic inflammation of the risk. In UC, histological remission may be a long-term therapeutic goal but its role in CD remains unclear. Different scores have been developed to quantify the inflammatory activity of IBD patients and the response to treatment. The aim of this review is to present the main activity scores used in the follow-up of IBD, their interest, their evaluation and their limitations.
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Affiliation(s)
- Camille Boulagnon-Rombi
- Service de pathologie, CHU de Reims, 51092 Reims, France; CNRS, MEDyC UMR 7369, université de Reims Champagne Ardenne, 51097 Reims, France.
| | - Aude Marchal
- Émile-Gallé groupe, centre de pathologie, Nancy, France
| | | | - Magali Svrcek
- Université de la Sorbonne, Paris, France; Service d'anatomie et cytologie pathologiques, Sorbonne université, hôpital Saint-Antoine, AP-HP, Paris, France
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34
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Cohen NA, Steinberg JM, Silfen A, Traboulsi C, Rodriguez TG, Singer JM, Patel S, Cohen RD, Dalal SR, Sakuraba A, Pekow J, Micic D, Rubin DT. Endo-histologic Normalization Is Achievable with Tofacitinib and Is Associated with Improved Clinical Outcomes. Dig Dis Sci 2023; 68:1464-1472. [PMID: 36242686 DOI: 10.1007/s10620-022-07716-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 10/05/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Recent real-world effectiveness studies investigating tofacitinib have been encouraging. Questions remain regarding the long-term effectiveness and safety of tofacitinib, effect on endoscopic remission rates, histologic changes, and alterations in fecal calprotectin levels. METHODS This retrospective study includes consecutive patients with inflammatory bowel disease (IBD) who initiated tofacitinib therapy. We reviewed electronic medical records for demographic and clinical data, as well as all adverse events and hospitalizations. All patients receiving tofacitinib were included in the safety analysis and only patients with ulcerative colitis (UC) were included in the effectiveness analysis. RESULTS 119 patients with IBD (97 UC, 12 CD, and 10 pouchitis) seen at our center between 2014 and 2020 were included in this study. Median follow-up was 32 weeks (interquartile range (IQR) 3-252). Clinical response and remission were observed in 70% and 21%, 59% and 33%, and 49%, and 37% at weeks 8, 24, and 52, respectively. Endo-histologic healing was achieved by 11%, 25%, and 37.5% of patients at weeks 8, 24, and 52, respectively. Histologic normalization occurred as early as 24 weeks in this cohort and was achieved by 26% of patients in endoscopic remission. Overall, there were 27 (25%) adverse events with 6 (5%) resulting in treatment discontinuation. There were 11 (10%) infections, none required treatment discontinuation. Ten (10.3%) patients underwent colectomy during the follow-up period. There were no cardiovascular adverse events in the cohort during follow-up. CONCLUSION This study demonstrates the effectiveness and long-term safety of tofacitinib in patients with UC. Importantly, we show that the endpoint of endo-histologic healing is achievable with tofacitinib and can occur as early as week 8 of therapy.
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Affiliation(s)
- Nathaniel A Cohen
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Joshua M Steinberg
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Alexa Silfen
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Cindy Traboulsi
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Tina G Rodriguez
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Jorie M Singer
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Shivani Patel
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Russell D Cohen
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Sushila R Dalal
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Atsushi Sakuraba
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Joel Pekow
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Dejan Micic
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA.
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35
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Seong G, Song JH, Kim JE, Kim TJ, Kim ER, Hong SN, Chang DK, Kim SH, Ha SY, Kim YH. Histologic Activity and Steroid Use History Are Risk Factors of Clinical Relapse in Ulcerative Colitis With Mayo Endoscopic Subscore of 0 or 1. Inflamm Bowel Dis 2023; 29:238-244. [PMID: 35396998 DOI: 10.1093/ibd/izac075] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND The treatment goal of ulcerative colitis (UC) has changed from the control of symptoms to mucosal healing, previously evaluated mainly by endoscopy. Recently, the importance of histologic activity has emerged. Therefore, this study aimed to investigate the risk of clinical relapse according to histologic activity in UC with a Mayo endoscopic subsccore (MES) of 0 or 1. METHODS In a retrospective cohort after our center's biopsy guideline for UC was instituted, 492 UC patients with an MES of 0 or 1 were enrolled and analyzed. The primary outcome was the development of a clinical relapse including changes in medication, hospitalization, colectomy, and the development of colorectal cancer during the follow-up period. RESULTS During the median 549 days of follow-up, 92 (18.7%) patients had a clinical relapse. All the patients changed their medication, including 4 hospitalized patients. Histologic activity defined by a Geboes score of ≧3.1 (hazard ratio [HR], 1.732; P = .035) and steroid use history (HR, 1.762; P = .008) were independent factors associated with clinical relapse. When stratified, the 1- and 2-year incidence rates of clinical relapse were 4.1% and 10.6%, respectively, for patients with histologic improvement and no steroid use history, whereas the rates were 23.9% and 39.4% for patients with histologic activity and steroid use history. CONCLUSIONS In UC with an MES of 0 or 1, histologic activity and steroid use history can be used to stratify the risk of clinical relapse.
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Affiliation(s)
- Gyeol Seong
- Department of Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Korea
| | - Joo Hye Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Eun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Jun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun Ran Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seok-Hyung Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Yun Ha
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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36
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Friedrich M, Travis S. Shining a Light on Barrier Function. Gastroenterology 2023; 164:184-186. [PMID: 36410444 DOI: 10.1053/j.gastro.2022.11.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 11/15/2022] [Indexed: 11/21/2022]
Affiliation(s)
- Matthias Friedrich
- Translational Gastroenterology Unit, Nuffield Department of Medicine and, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and, Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
| | - Simon Travis
- Translational Gastroenterology Unit, Nuffield Department of Medicine and, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and, Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
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Pudipeddi A, Fung C, Christensen B, Bryant RV, Subramaniam K, Chetwood J, Paramsothy S, Leong RW. Knowledge and attitudes towards the use of histological assessments in ulcerative colitis by gastroenterologists vs pathologists. World J Gastroenterol 2023; 29:378-389. [PMID: 36687119 PMCID: PMC9846936 DOI: 10.3748/wjg.v29.i2.378] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 11/04/2022] [Accepted: 12/23/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis (UC). However, the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is unknown.
AIM To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and pathologists.
METHODS A prospective, cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was conducted. The survey consisted of 34 questions to assess gastroenterologists’ and pathologists’ knowledge (score out of 19) and attitudes towards histological assessment in UC. Survey questions were formulated using the European Crohn’s and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting guidelines. It included knowledge of histological assessment of disease activity and dysplasia, knowledge of histological scoring systems for ulcerative colitis, uptake of histology scoring systems in routine practice, attitudes towards the role of histological activity, and the use of histological activity in clinical scenarios.
RESULTS Of 89 responders (77 gastroenterologists, 12 pathologists), there was almost universal acceptance that histological assessment should form part of UC evaluation [95% gastroenterologists, 92% pathologists]. However, gastroenterologists reported that 92% of their pathologists do not use a histological scoring system. Utilisation of a formal histological scoring system was preferred by 77% of gastroenterologists and 58% of pathologists. Both groups lacked awareness of the Geboes Score, Nancy Index and Robarts Histopathological Index scoring systems with 91%, 87%, and 92% of gastroenterologists respectively; and 83%, 83%, and 92% pathologists respectively, being uncertain of scoring systems’ remission definitions. Histology knowledge score was not significantly different between gastroenterologists and pathologists [9/19 (IQR: 8-11) vs 8/19 (IQR: 7-10), P = 0.54]. Higher knowledge scores were predicted by hospital attending gastroenterologists (P = 0.004), participation in inflammatory bowel disease (IBD) multidisciplinary teams (P = 0.009), and self-declared IBD sub-specialist (P = 0.03).
CONCLUSION Histological remission is a recognised target for both gastroenterologists and pathologists. Despite this, knowledge of histological scoring systems and their utilisation is poor.
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Affiliation(s)
- Aviv Pudipeddi
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
| | - Caroline Fung
- Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney 2139, Australia
| | - Britt Christensen
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne 3050, Australia
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
| | - Robert V Bryant
- Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Adelaide 5011, Australia
| | - Kavitha Subramaniam
- Gastroenterology and Hepatology Unit, Canberra Hospital, Canberra 2605, Australia
- Australian National University Medical School, Australian National University, Canberra 2601, Australia
| | - John Chetwood
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
| | - Sudarshan Paramsothy
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
- Faculty of Medicine and Health Sciences, Macquarie University Hospital, Sydney 2109, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
- Faculty of Medicine and Health Sciences, Macquarie University Hospital, Sydney 2109, Australia
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38
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Kurimoto N, Nishida Y, Hosomi S, Itani S, Kobayashi Y, Nakata R, Ominami M, Nadatani Y, Fukunaga S, Otani K, Tanaka F, Nagami Y, Taira K, Kamata N, Fujiwara Y. Neutrophil-to-lymphocyte ratio may predict clinical relapse in ulcerative colitis patients with mucosal healing. PLoS One 2023; 18:e0280252. [PMID: 36634124 PMCID: PMC9836288 DOI: 10.1371/journal.pone.0280252] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 12/22/2022] [Indexed: 01/13/2023] Open
Abstract
Endoscopic mucosal healing (MH) is an important treatment goal for patients with ulcerative colitis (UC). The neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and has been reported to be a useful predictive marker for UC. This study aimed to evaluate the clinical utility of the NLR for predicting clinical relapse in UC patients with MH. We retrospectively enrolled patients with UC who underwent colonoscopy at the Osaka City University Hospital between January 2010 and December 2010, whose Mayo Endoscopic Subscore was 0 or 1. The correlation between the incidence of relapse and demographic factors, including the NLR, was analyzed. We included 129 patients in the present study. The median NLR at the time of endoscopy was 1.98, and differences in the high NLR group and the low NLR group were compared. During a median follow-up period of 46.4 months, 58 patients (45.0%) experienced relapse. The cumulative relapse-free rate was significantly higher in the low NLR group than in the high NLR group (P = 0.03, log-rank test). Multivariate analysis identified high NLR as an independent prognostic factor for clinical relapse (hazard ratio, 1.74; 95% confidence interval, 1.02-2.98; P = 0.04). NLR is a novel and useful predictor of clinical relapse in UC patients with MH, and it can potentially be a strong indicator to determine the appropriate treatment strategy and decision-making in clinical practice.
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Affiliation(s)
- Noriyuki Kurimoto
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yu Nishida
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Shuhei Hosomi
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
- * E-mail:
| | - Shigehiro Itani
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yumie Kobayashi
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Rieko Nakata
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Masaki Ominami
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yuji Nadatani
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Shusei Fukunaga
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Koji Otani
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Fumio Tanaka
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yasuaki Nagami
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Koichi Taira
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
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Chen R, Li C, Chao K, Tie Y, Zheng J, Guo H, Zeng Z, Li L, Chen M, Zhang S. Neutrophil-to-lymphocyte ratio for predicting postoperative recurrence in Crohn's disease patients with isolated anastomotic lesions. Therap Adv Gastroenterol 2023; 16:17562848231165129. [PMID: 37025498 PMCID: PMC10071151 DOI: 10.1177/17562848231165129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 03/06/2023] [Indexed: 04/08/2023] Open
Abstract
Background Patients with isolated anastomotic lesions (iAL) are common in postoperative Crohn's disease (CD) and have heterogeneous prognosis. Objectives To investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in CD patients with iAL. Design A bicenter retrospective cohort study. Methods CD patients who received ileocolonic resection from 2013 and 2020 and had a modified Rutgeerts score of i2a were recruited. NLR was determined within 1 week around the initial endoscopy after ileocolectomy. The primary outcome was clinical recurrence. Kaplan-Meier method and Cox hazard regression analysis were utilized to assess the association between candidate variables and outcomes of interest. Results In total, 411 postoperative CD patients were preliminarily reviewed and 83 patients were eligible. In total, 36 (48.6%) patients experienced clinical recurrence with a median follow-up time of 16.3 (interquartile range, 9.7-26.3) months. NLR > 2.45 and age at surgery >45 years had higher cumulative incidence of clinical recurrence in the Kaplan-Meier analysis. After adjusted for potential confounders, NLR > 2.45 was the only independent risk factor for clinical recurrence, with an adjusted hazard ratio (HR) of 2.88 [95% confidence interval (CI), 1.39-6.00; p = 0.005]. Furthermore, a risk score based on NLR and age at surgery were built to further stratify patients. Compared to those who scored 0, patients with a score of 1 and 2 had an adjusted HR of 2.48 (95% CI, 1.22-5.02) and 6.97 (95% CI, 2.19-22.16) for developing clinical recurrence, respectively. Conclusions NLR is a promising prognostic biomarker for CD patients with iAL. The utilization of NLR and the risk score to stratify patients may facilitate the personalized management in patients with iAL.
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Affiliation(s)
| | | | - Kang Chao
- Division of Gastroenterology, The Sixth
Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yizhe Tie
- Division of Gastroenterology, The First
Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
- Department of Clinical Medicine, Zhongshan
School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Jieqi Zheng
- Division of Gastroenterology, The First
Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
- Department of Clinical Medicine, Zhongshan
School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Huili Guo
- Division of Gastroenterology, The Sixth
Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhirong Zeng
- Division of Gastroenterology, The First
Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Li Li
- Division of Gastroenterology, The First
Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2,
Guangzhou 510080, China
| | - Minhu Chen
- Division of Gastroenterology, The First
Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2,
Guangzhou 510080, China
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Steinsbø Ø, Carlsen A, Aasprong OG, Aabakken L, Tvedt-Gundersen E, Bjørkhaug S, Gjerde R, Normann Karlsen L, Grimstad T. Histologic healing and factors associated with complete remission following conventional treatment in ulcerative colitis. Therap Adv Gastroenterol 2022; 15:17562848221140659. [PMID: 36506747 PMCID: PMC9729989 DOI: 10.1177/17562848221140659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 11/05/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Endoscopic and histological activity scores in ulcerative colitis (UC) are associated with clinical outcomes and have become important targets of clinical trials. However, these endpoints have been scarcely investigated in patients receiving only conventional treatment. OBJECTIVE We aimed to assess the deep and complete remission rates after 3 months of conventional treatment in patients with newly diagnosed UC with moderate to severe endoscopic activity. We also aimed to investigate whether selected clinical and biochemical variables at baseline were associated with complete remission status after 3 months. DESIGN This was a prospective cohort study. METHODS Newly diagnosed patients with active UC commencing 5-aminosalicylate, corticosteroid, and/or azathioprine treatment were consecutively included. Clinical, biochemical, endoscopic, and histological data were collected at baseline and after 3 months. Rates of clinical remission (Partial Mayo Score ⩽ 2), mucosal healing (Mayo Endoscopic Score ⩽ 1), and histologic healing (Nancy Index ⩽ 1) were determined. Deep remission was assessed as clinical remission plus mucosal healing and complete remission as deep remission plus histologic healing. Predictors of complete remission were identified by logistic regression. RESULTS A total of 180 patients were included in the study. Deep remission and complete remission occurred in 62.8% and 42.2% of patients, respectively. Thus, of patients in deep remission one-third had persistent histologic activity. Histologic activity in mucosally healed patients was associated with higher symptom scores and faecal calprotectin levels. Of baseline variables, less endoscopic distribution and disease activity showed strongest association with achieving complete remission, and limited distribution in combination with moderate activity gave highest odds for complete remission (odds ratio: 4.1, 95% confidence interval: 7.69-2.18). CONCLUSION In patients with mucosal healing, persistent histologic activity was a common finding and was associated with increased disease activity. Pancolitis and severe inflammatory activity at baseline were associated with lower complete remission rates.
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Affiliation(s)
| | - Arne Carlsen
- Department of Medical Gastroenterology, Stavanger University Hospital, Stavanger, Norway
| | | | - Lars Aabakken
- Department of Medical Gastroenterology, Rikshospitalet University Hospital, Oslo, Norway
| | - Espen Tvedt-Gundersen
- Department of Medical Gastroenterology, Stavanger University Hospital, Stavanger, Norway
| | - Steinar Bjørkhaug
- Department of Medical Gastroenterology, Stavanger University Hospital, Stavanger, Norway
| | - Rune Gjerde
- Department of Medical Gastroenterology, Stavanger University Hospital, Stavanger, Norway
| | - Lars Normann Karlsen
- Department of Medical Gastroenterology, Stavanger University Hospital, Stavanger, Norway
| | - Tore Grimstad
- Department of Medical Gastroenterology, Stavanger University Hospital, Stavanger, Norway,Department of Clinical Science, University of Bergen, Bergen, Norway
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Krugliak Cleveland N, Bressler B, Siegel CA. A Summary of the BRIDGe Summit on Damage-Related Progression of Ulcerative Colitis: Establishing Research Priorities. Gastroenterology 2022; 163:1505-1509. [PMID: 35964690 PMCID: PMC10008123 DOI: 10.1053/j.gastro.2022.08.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/02/2022] [Accepted: 08/06/2022] [Indexed: 12/20/2022]
Affiliation(s)
| | - Brian Bressler
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Corey A Siegel
- Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
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Murphy ME, Bhattacharya S, Axelrad JE. Diagnosis and Monitoring of Ulcerative Colitis. Clin Colon Rectal Surg 2022; 35:421-427. [PMID: 36591402 PMCID: PMC9797286 DOI: 10.1055/s-0042-1758047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Ulcerative colitis is one of the two main subtypes of inflammatory bowel disease, along with Crohn's disease. Understanding the clinical and endoscopic features of ulcerative colitis is critical in achieving a timely diagnosis. An initial evaluation includes assessing clinical symptoms, inflammatory markers, endoscopic findings, and determination of the presence or absence of extraintestinal manifestations. Initial disease management should consider disease severity at the time of diagnosis as well as prognostication, or the determination of risk factors present with a high likelihood of severe disease in the future. Once appropriate therapy has been initiated, ongoing monitoring is crucial, which may include repeated clinical assessments over time, measuring noninvasive markers of inflammation, and endoscopic and histologic reevaluation. An important aspect of disease monitoring in ulcerative colitis is dysplasia surveillance; there are many patient-specific risk factors which influence surveillance strategies. Utilizing appropriate surveillance techniques is necessary for early detection of dysplasia and colorectal neoplasia.
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Affiliation(s)
- Megan E. Murphy
- Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center at NYU Langone Health, NYU Grossman School of Medicine, New York, New York
| | - Sumona Bhattacharya
- Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center at NYU Langone Health, NYU Grossman School of Medicine, New York, New York
| | - Jordan E. Axelrad
- Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center at NYU Langone Health, NYU Grossman School of Medicine, New York, New York
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Fabian O, Bajer L. Histopathological assessment of the microscopic activity in inflammatory bowel diseases: What are we looking for? World J Gastroenterol 2022; 28:5300-5312. [PMID: 36185628 PMCID: PMC9521520 DOI: 10.3748/wjg.v28.i36.5300] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/11/2022] [Accepted: 09/07/2022] [Indexed: 02/06/2023] Open
Abstract
Advances in diagnostics of inflammatory bowel diseases (IBD) and improved treatment strategies allowed the establishment of new therapeutic endpoints. Currently, it is desirable not only to cease clinical symptoms, but mainly to achieve endoscopic remission, a macroscopic normalization of the bowel mucosa. However, up to one-third of IBD patients in remission exhibit persisting microscopic activity of the disease. The evidence suggests a better predictive value of histology for the development of clinical complications such as clinical relapse, surgical intervention, need for therapy escalation, or development of colorectal cancer. The proper assessment of microscopic inflammatory activity thus became an important part of the overall histopathological evaluation of colonic biopsies and many histopathological scoring indices have been established. Nonetheless, a majority of them have not been validated and no scoring index became a part of the routine bioptic practice. This review summarizes a predictive value of microscopic disease activity assessment for the subsequent clinical course of IBD, describes the most commonly used scoring indices for Crohn's disease and ulcerative colitis, and comments on current limitations and unresolved issues.
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Affiliation(s)
- Ondrej Fabian
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
- Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University and Thomayer Hospital, Prague 14059, Czech Republic
| | - Lukas Bajer
- Hepatogastroenterology Department, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
- Institute of Microbiology, Czech Academy of Sciences, Prague 14220, Czech Republic
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D’Amico F, Fiorino G, Solitano V, Massarini E, Guillo L, Allocca M, Furfaro F, Zilli A, Bonovas S, Magro F, Peyrin‐Biroulet L, Danese S. Ulcerative colitis: Impact of early disease clearance on long‐term outcomes ‐ A multicenter cohort study. United European Gastroenterol J 2022; 10:775-782. [PMID: 36107109 PMCID: PMC9486490 DOI: 10.1002/ueg2.12288] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 07/28/2022] [Indexed: 11/24/2022] Open
Abstract
Background Clinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC. Objective We aimed to evaluate the impact of disease clearance on long‐term outcomes in UC patients. Methods A multicenter retrospective cohort study was conducted at the Humanitas Research Hospital‐IRCCS (Italy) and at the Nancy University Hospital (France) between 2014 and 2021. Disease clearance in UC was defined as simultaneous clinical (partial‐Mayo score ≤2), endoscopic (endoscopic‐Mayo score = 0), and histological (Nancy index = 0) remission, and patients were monitored over a long‐time follow‐up (≥12 months), to compare the occurrence of negative outcomes. Results A total of 494 patients with UC was included in the study (269, 54.4% males). Disease clearance was present in 109 patients (22.1%) at baseline. Median follow up was 24 months. Patients with disease clearance were associated to a significantly lower risk of UC‐related hospitalization compared with the control group (5.5% vs. 23.1%; p < 0.001) at last observation. Similarly, a lower rate of surgeries was detected in patients with disease clearance at baseline compared with those without (1.8% vs. 10.9%; p = 0.003). The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk of hospitalization (log‐rank p < 0.0001) and surgery (log‐rank p < 0.00095). Conclusion In UC patients with early disease clearance are at significant lower risk for hospitalization and surgery. Disease clearance should be considered as a new composite outcome.
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Affiliation(s)
- Ferdinando D’Amico
- Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and Vita‐Salute San Raffaele University Milan Italy
- Department of Biomedical Sciences Humanitas University Milan Italy
| | - Gionata Fiorino
- Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and Vita‐Salute San Raffaele University Milan Italy
| | | | | | - Lucas Guillo
- Department of Gastroenterology University Hospital of Marseille Nord University of Aix‐Marseille Marseille France
| | - Mariangela Allocca
- Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and Vita‐Salute San Raffaele University Milan Italy
| | - Federica Furfaro
- Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and Vita‐Salute San Raffaele University Milan Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and Vita‐Salute San Raffaele University Milan Italy
| | - Stefanos Bonovas
- Department of Biomedical Sciences Humanitas University Milan Italy
| | - Fernando Magro
- Department of Gastroenterology Centro Hospitalar São João Porto Portugal
| | - Laurent Peyrin‐Biroulet
- Department of Gastroenterology University of Lorraine CHRU‐Nancy Nancy France
- University of Lorraine Inserm NGERE Nancy France
| | - Silvio Danese
- Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and Vita‐Salute San Raffaele University Milan Italy
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Ruan GC, Jin X, Zhou WX, You Y, Iacucci M, Ghosh S, Gui XY, Li J, Qian JM. External validation of the Paddington International Virtual Electronic ChromoendoScopy ScOre as a good endoscopic score to define mucosal healing and predict long-term clinical outcomes in ulcerative colitis. J Dig Dis 2022; 23:446-454. [PMID: 36121308 DOI: 10.1111/1751-2980.13126] [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: 07/21/2022] [Revised: 09/01/2022] [Accepted: 09/15/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To define endoscopic and histological remission in ulcerative colitis (UC) accurately, several scoring systems have been established. A novel virtual electronic chromoendoscopy score, the Paddington International Virtual ChromoendoScopy ScOre (PICaSSO), was developed, validated, and reproduced to assess inflammation grade and predict patient prognosis. We externally verified and validated the clinical value of PICaSSO in UC patients. METHODS This prospective study enrolled 63 UC patients. The Mayo endoscopic score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO were adopted for endoscopic evaluation. All biopsy samples were scored using the Robarts histological index (RHI), Nancy histological index (NHI), and "Extent, Chronicity, Activity, Plus additional findings" (ECAP) score. Patients with an endoscopic MES of 0-1 at baseline were followed up during a median time of 23.5 months. RESULTS PICaSSO was strongly correlated with other endoscopic and histological scoring systems. PICaSSO ≤3 had advantages in assessing histological remission (HR), with the highest accuracy of 88.9% for ECAP-HR. Relapse-free survival rates were significantly different between patients with MES 0 and MES 1 and patients with PICaSSO ≤3 and >3 (P = 0.010 and 0.018, respectively). CONCLUSIONS PICaSSO was externally validated with strong correlations with other endoscopic and histological scoring systems in UC, and PICaSSO-ER might potentially predict a better long-term clinical outcome in UC patients.
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Affiliation(s)
- Ge Chong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xin Jin
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei Xun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yan You
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Subrata Ghosh
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Xian Yong Gui
- Department of Pathology, School of Medicine, University of Washington, Seattle, Washington, USA
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jia Ming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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Christensen B. Histologic Healing in Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y) 2022; 18:466-468. [PMID: 36397814 PMCID: PMC9666803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Affiliation(s)
- Britt Christensen
- Head of Inflammatory Bowel Disease Unit Gastroenterology Department The Royal Melbourne Hospital Melbourne, Australia
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Zhou Z, Zhang Y, Pan Y, Yang X, Li L, Gao C, He C. A Novel Neutrophil-Based Biomarker to Monitor Disease Activity and Predict Response to Infliximab Therapy in Patients With Ulcerative Colitis. Front Med (Lausanne) 2022; 9:872831. [PMID: 35572985 PMCID: PMC9092064 DOI: 10.3389/fmed.2022.872831] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/17/2022] [Indexed: 11/13/2022] Open
Abstract
Background Ulcerative colitis (UC) is characterized by refractory and recurrent mucosal inflammation, leading to a substantial healthcare burden. Diagnostic biomarkers predicting disease activity and treatment response remain elusive. To evaluate the application value of a novel neutrophil-based index (the neutrophil-to-albumin ratio, NAR) as a novel diagnostic biomarker in patients with UC and a predictive marker for disease activity and response to infliximab (IFX) therapy. Methods Clinical characteristics and laboratory parameters of enrolled subjects (patients with UC and healthy controls) were retrieved from the electronic medical record database of our hospital. Serum cytokine and fecal calprotectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR). Results We found that NAR, which had not yet been explored in UC, was significantly increased in patients with UC (n = 146) compared to that in controls (n = 133) (1.95 ± 0.41 vs. 1.41 ± 0.23, p < 0.0001). NAR showed a positive association with the disease activity and inflammatory load in patients with UC. Pre-treatment NAR was significantly lower in IFX responders than that in non-responders (2.18 ± 0.29 vs. 2.44 ± 0.21, p = 0.0118), showing a significant ability to discriminate initial responders from primary non-responders to IFX induction therapy (AUC = 0.7866, p = 0.0076). Moreover, pre-treatment NAR predicted postinduction serum IFX trough level. Conclusion Our study provides evidences to utilize NAR in the diagnosis, activity monitoring, and IFX response prediction in patients with UC.
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Affiliation(s)
- Zhou Zhou
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yinghui Zhang
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yan Pan
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xue Yang
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Liangping Li
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Caiping Gao
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Chong He
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.,Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
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Abstract
Interleukin [IL]-23 is a member of the IL-12 family of cytokines and has been implicated in multiple inflammatory disorders including psoriasis, psoriatic arthritis, and the inflammatory bowel diseases [IBDs]. Blockade of both IL-12 and IL-23 using an antibody that targets a shared subunit is highly effective in treating psoriasis, and recent data suggest similar efficacy in IBD with minimal adverse events. In this review, we summarise published data on the efficacy of anti-IL-12/23 therapies in IBD as well as emerging data on more selective anti-IL-23 specific therapies. Last, we discuss novel therapeutics under development which target the IL-23 pathway in unique ways and suggest that a biomarker-driven approach will soon guide clinicians to prescribe anti-IL-23 therapies to the patients most likely to respond to them.
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Affiliation(s)
- Benjamin D McDonald
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - Emma C Dyer
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
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Gui X, Bazarova A, Del Amor R, Vieth M, de Hertogh G, Villanacci V, Zardo D, Parigi TL, Røyset ES, Shivaji UN, Monica MAT, Mandelli G, Bhandari P, Danese S, Ferraz JG, Hayee B, Lazarev M, Parra-Blanco A, Pastorelli L, Panaccione R, Rath T, Tontini GE, Kiesslich R, Bisschops R, Grisan E, Naranjo V, Ghosh S, Iacucci M. PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system. Gut 2022; 71:889-898. [PMID: 35173041 PMCID: PMC8995819 DOI: 10.1136/gutjnl-2021-326376] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/20/2022] [Indexed: 12/17/2022]
Abstract
UNLABELLED Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity. METHODS Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies. RESULTS PHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients' risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy. CONCLUSIONS PHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission.
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Affiliation(s)
- Xianyong Gui
- Pathology, University of Washington School of Medicine, Seattle, WA, USA
| | - Alina Bazarova
- Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- Institute for Biological Physics, University of Cologne, Koln, Germany
| | - Rocìo Del Amor
- Instituto de Investigación e Innovación en Bioingeniería, I3B, Universitat Politecnica de Valencia, Valencia, Spain
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth GmbH, Bayreuth, Germany
- Institute of Pathology, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany
| | - Gert de Hertogh
- Department of Pathology, KU Leuven University Hospitals Leuven, Leuven, Belgium
| | | | - Davide Zardo
- Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Tommaso Lorenzo Parigi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Elin Synnøve Røyset
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway
| | - Uday N Shivaji
- Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- Gastroenterology, National Institute of Health Research Birmingham Biomedical Research Unit, Birmingham, UK
| | | | - Giulio Mandelli
- Department of Pathology, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Pradeep Bhandari
- Department of Gastroenterology, Queen Alexandra Hospital, Portsmouth, UK
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, Università Vita Salute San Raffaele, Milano, Italy
- Department of Gastroenterology and Endoscopy, San Raffaele Hospital, Milano, Italy
| | - Jose G Ferraz
- Division of Gastroenterology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Bu'Hussain Hayee
- King's Health Partners Institute for Therapeutic Endoscopy, King's College Hospital NHS Foundation Trust, London, UK
| | - Mark Lazarev
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Adolfo Parra-Blanco
- Department of Gastroenterology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Luca Pastorelli
- Gastroenterology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Remo Panaccione
- Division of Gastroenterology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Timo Rath
- Department of Gastoenterology, University of Erlangen Nuremberg-Nuremberg Campus, Nurnberg, Germany
| | - Gian Eugenio Tontini
- Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Ralf Kiesslich
- Department of Gastroenterology, Helios HSK, Wiesbaden, Germany
| | - Raf Bisschops
- Department of Gastroenterology, KU Leuven University Hospitals Leuven, Leuven, Belgium
| | - Enrico Grisan
- School of Engineering, London South Bank University, London, UK
- Department of Information Engineering, Università degli Studi di Padova, Padova, Italy
| | - Valery Naranjo
- Instituto de Investigación e Innovación en Bioingeniería, I3B, Universitat Politecnica de Valencia, Valencia, Spain
| | - Subrata Ghosh
- Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- APC Microbiome, Ireland, University College Cork, Cork, Ireland
| | - Marietta Iacucci
- Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- Gastroenterology, National Institute of Health Research Birmingham Biomedical Research Unit, Birmingham, UK
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Nardone OM, Snir Y, Hodson J, Cannatelli R, Labarile N, Siau K, Hassan C, Yanai H, Dotan I, Ghosh S, Iacucci M. Advanced technology for assessment of endoscopic and histological activity in ulcerative colitis: a systematic review and meta-analysis. Therap Adv Gastroenterol 2022; 15:17562848221092594. [PMID: 35509428 PMCID: PMC9058346 DOI: 10.1177/17562848221092594] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 03/17/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Advanced endoscopic technologies led to significant progress in the definition of endoscopic remission of ulcerative colitis (UC) and correlate better with histological changes, compared with standard endoscopy. However, while studies have assessed the diagnostic accuracy of endoscope technologies individually, there are currently limited data comparing between technologies. As such, the aim of this systematic review was to pool data from the existing literature and compare the correlations between endoscopy and histologic disease activity scores across endoscope technologies. METHODS We searched PubMed and Embase until February 2021 for eligible studies reporting the correlation between endoscopy and histology activity scores in UC. Studies were grouped by endoscope technology as standard-definition white light (SD-WLE), high-definition white light (HD-WLE) or electronic virtual chromoendoscopy (VCE) and comparisons made between these groups. RESULTS A total of N = 27 studies were identified, of which N = 12 were included in a meta-analysis of correlations between endoscopic and histological activity scores. Combining these studies identified considerable heterogeneity (I 2: 89-93%) and returned a pooled correlation coefficient (ρ) for the SD-WLE group of 0.74, which did not differ significantly from HD-WLE (ρ: 0.65, p = 0.521) or VCE (ρ: 0.70, p = 0.801). In addition, N = 4 studies reported the accuracy of endoscopic activity scores on WLE and VCE to diagnose histological remission. Pooling these found significantly higher accuracy for VCE, compared with WLE [risk ratio: 1.13, 95% confidence interval (CI): 1.07-1.19, p < 0.001]. CONCLUSION Activity scores assessed using endoscopy are strongly correlated with activity on histology regardless of endoscopic technology. VCE seems to be more accurate in predicting histological remission than WLE. However, given the heterogeneity between the included studies, head-to-head trials are warranted to confirm these findings.
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Affiliation(s)
| | | | | | - Rosanna Cannatelli
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Nunzia Labarile
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Keith Siau
- Institute for Translational Medicine, Queen Elizabeth Hospital, UHBFT, Birmingham, UK,Department of Gastroenterology, Royal Cornwall Hospitals NHS Trust, Truro, UK
| | - Cesare Hassan
- Department of Gastroenterology, Nuovo Regina Margherita Hospital, Roma, Italy
| | - Henit Yanai
- Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petach-Tikva, Israel,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petach-Tikva, Israel,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Subrata Ghosh
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK,NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Trust, University of Birmingham, Birmingham, UK,NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK,APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
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