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Eglinton T. Editorial: Examining Perianal Fistulising Crohn's Disease Through the Lens of Wound Repair. Aliment Pharmacol Ther 2025; 61:1073-1074. [PMID: 39954257 DOI: 10.1111/apt.70001] [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: 01/18/2025] [Revised: 01/20/2025] [Accepted: 01/20/2025] [Indexed: 02/17/2025]
Affiliation(s)
- Tim Eglinton
- Department of Surgery and Critical Care, University of Otago, Christchurch, New Zealand
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2
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McCurdy JD, Hartley I, Behrenbruch C, Hart A, Tozer P, Ding NS. Management of Perianal Fistulizing Crohn's Disease According to Principles of Wound Repair. Aliment Pharmacol Ther 2025; 61:600-613. [PMID: 39757535 DOI: 10.1111/apt.18466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/14/2024] [Accepted: 12/16/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND Perianal fistulizing Crohn's disease (PFCD) is a challenging and debilitating phenotype of Crohn's disease that can negatively affect quality of life. Studies have begun to uncover the physiologic mechanisms involved in wound repair as it relates to PFCD and how aberrations in these mechanisms may contribute to fistula persistence. AIMS To review the physiologic and pathophysiologic mechanisms of wound repair in PFCD and how specific therapeutic strategies may impact their outcomes. METHODS We reviewed the latest published literature on wound repair as it relates to PFCD. RESULTS Wound repair can be categorised into three overlapping biological phases: localised inflammation, cell recruitment/proliferation and tissue remodelling. Each is tightly regulated since insufficient or excessive activation can result in, respectively, chronic wounds and fibrotic tissue, both of which can impair organ function. In PFCD, the outcomes of wound repair include restitution (complete healing), epithelialisation and chronic wounds. Treatment of PFCD should take into consideration the distinct phases of wound repair. Therefore, the ability to differentiate between each phase of wound repair and their outcomes may help physicians deliver the most effective treatment strategy at the most appropriate time. CONCLUSIONS This review provides a comprehensive overview of the phases of wound repair and specific treatment strategies for each to provide clinicians with a rational framework for managing PFCD.
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Affiliation(s)
- Jeffrey D McCurdy
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Imogen Hartley
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- The University of Melbourne, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Corina Behrenbruch
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- The University of Melbourne, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | | | | | - Nik S Ding
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- The University of Melbourne, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
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3
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Singh JP, Aleissa M, Drelichman ER, Mittal VK, Bhullar JS. Navigating the complexities of perianal Crohn's disease: Diagnostic strategies, treatment approaches, and future perspectives. World J Gastroenterol 2024; 30:4745-4753. [PMID: 39610776 PMCID: PMC11580605 DOI: 10.3748/wjg.v30.i44.4745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/25/2024] [Accepted: 10/24/2024] [Indexed: 11/12/2024] Open
Abstract
This article discusses the literature review article by Pacheco et al published in July 2024; the authors provided good reviews of perianal Crohn's disease (CD), and challenges faced by clinicians in the management. CD, characterized by its chronic and relapsing nature, is an idiopathic condition that can involve any segment of the gastrointestinal tract. Perianal disease impacts up to 40% of patients with CD, with perianal fistulas constituting up to 80% of perianal lesions. Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients. The management focuses on controlling the perianal sepsis and treating luminal CD. Biologics are crucial to the treatment approach, and results have been encouraging. The surgery focuses on controlling the sepsis, with more definitive treatments being fistula surgery, fecal diversion, and proctectomy as the last resort. This manuscript briefly describes the burden of CD, the challenges posed by perianal CD, and the role of different treatment modalities from colorectal surgeon's perspective.
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Affiliation(s)
- Jai P Singh
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Southfield, MI 48075, United States
| | - Maryam Aleissa
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Ernesto R Drelichman
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Vijay K Mittal
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Jasneet S Bhullar
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
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4
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Ding K, Kong J, Li L, Selaru FM, Parian A, Mao HQ. Current and emerging therapeutic strategies for perianal fistula in Crohn's disease patients. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2024; 101:159-182. [PMID: 39521599 PMCID: PMC11753511 DOI: 10.1016/bs.apha.2024.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
The long-term remission rates achieved with current treatment options for Crohn's disease with perianal fistula (CD-PAF)-including antibiotics, biologics, immunomodulators, and Janus kinase inhibitors, often combined with advanced surgical interventions-remain unsatisfactory. This chapter explores several innovative biomaterials-based solutions, such as plugs, adhesives, fillers, and stem cell-based therapies. The key approaches and treatment outcomes of these advanced therapies are examined, focusing on their ability to modulate the immune response, promote tissue healing, and improve patient outcomes. Additionally, the chapter discusses future directions, including the optimization of biomaterial designs, enhancement of delivery and retention of regenerative therapies, and a deeper understanding of the underlying mechanisms of healing.
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Affiliation(s)
- Kailei Ding
- Institute for NanoBioTechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Materials Science and Engineering, Whiting School of Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jiayuan Kong
- Institute for NanoBioTechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Materials Science and Engineering, Whiting School of Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Ling Li
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Florin M Selaru
- Institute for NanoBioTechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Alyssa Parian
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
| | - Hai-Quan Mao
- Institute for NanoBioTechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Materials Science and Engineering, Whiting School of Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
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5
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Swaminathan A, Sparrow MP. Perianal Crohn's disease: Still more questions than answers. World J Gastroenterol 2024; 30:4260-4266. [PMID: 39492828 PMCID: PMC11525859 DOI: 10.3748/wjg.v30.i39.4260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 09/17/2024] [Accepted: 09/23/2024] [Indexed: 10/12/2024] Open
Abstract
In this editorial we comment on the article by Pacheco et al published in a recent issue of the World Journal of Gastroenterology. We focus specifically on the burden of illness associated with perianal fistulizing Crohn's disease (PFCD) and the diagnostic and therapeutic challenges in the management of this condition. Evolving evidence has shifted the diagnostic framework for PFCD from anatomical classification systems, to one that is more nuanced and patient-focused to drive ongoing decision making. This editorial aims to reflect on these aspects to help clinicians face the challenge of PFCD in day-to-day clinical practice.
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Affiliation(s)
- Akhilesh Swaminathan
- Department of Medicine, University of Otago, Christchurch 8011, Canterbury, New Zealand
- Department of Gastroenterology, Alfred Health, Melbourne 3004, Victoria, Australia
| | - Miles P Sparrow
- Department of Gastroenterology, The Alfred Hospital, Melbourne 3004, Victoria, Australia
- Department of Gastroenterology, Alfred Health and School of Translational Medicine, Monash University, Melbourne 3004, Victoria, Australia
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6
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Adamina M, Minozzi S, Warusavitarne J, Buskens CJ, Chaparro M, Verstockt B, Kopylov U, Yanai H, Vavricka SR, Sigall-Boneh R, Sica GS, Reenaers C, Peros G, Papamichael K, Noor N, Moran GW, Maaser C, Luglio G, Kotze PG, Kobayashi T, Karmiris K, Kapizioni C, Iqbal N, Iacucci M, Holubar S, Hanzel J, Sabino JG, Gisbert JP, Fiorino G, Fidalgo C, Ellu P, El-Hussuna A, de Groof J, Czuber-Dochan W, Casanova MJ, Burisch J, Brown SR, Bislenghi G, Bettenworth D, Battat R, Atreya R, Allocca M, Agrawal M, Raine T, Gordon H, Myrelid P. ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment. J Crohns Colitis 2024; 18:1556-1582. [PMID: 38878002 DOI: 10.1093/ecco-jcc/jjae089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Indexed: 07/28/2024]
Abstract
This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.
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Affiliation(s)
- Michel Adamina
- Department of Surgery, Cantonal Hospital of Fribourg & Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | - Silvia Minozzi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | | | | | - Maria Chaparro
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Bram Verstockt
- Department Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Belgium
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Rotem Sigall-Boneh
- Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson Medical Center, Holon, Israel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
| | - Giuseppe S Sica
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Università Tor Vergata, Roma, Italy
| | | | - Georgios Peros
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
| | - Konstantinos Papamichael
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nurulamin Noor
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Gordon William Moran
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
- Translational Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Christian Maaser
- Outpatients Department of Gastroenterology, University Teaching Hospital Lueneburg, Lueneburg, Germany
| | - Gaetano Luglio
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná [PUCPR], Curitiba, Brazil
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | | | | | - Nusrat Iqbal
- Department of Surgery, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Stefan Holubar
- Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Jurij Hanzel
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Department of of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - João Guedelha Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Javier P Gisbert
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | | | - Catarina Fidalgo
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
| | - Pierre Ellu
- Division of Gastroenterology, Mater Dei Hospital, l-Msida, Malta
| | - Alaa El-Hussuna
- OpenSourceResearch Organization [OSRC.Network], Aalborg, Denmark
| | - Joline de Groof
- Colorectal Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Wladyslawa Czuber-Dochan
- Florence Nightingale Faculty of Nursing-Midwifery and Palliative Care, King's College London, London, UK
| | - María José Casanova
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | | | | | - Dominik Bettenworth
- CED Schwerpunktpraxis, Münster and Medical Faculty of the University of Münster, Münster, Germany
| | - Robert Battat
- Division of Gastroenterology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Raja Atreya
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Mariangela Allocca
- IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy
| | - Manasi Agrawal
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Hannah Gordon
- Translational Gastroenterology and Liver Unit, Gastroenterology Office, University of Oxford, Oxford, UK
| | - Pär Myrelid
- Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Holmer AK, Hudesman D. Positioning Crohn's Disease Therapies in the Era of Small Molecules and Combination Therapies. Curr Gastroenterol Rep 2024; 26:263-272. [PMID: 38970743 DOI: 10.1007/s11894-024-00937-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2024] [Indexed: 07/08/2024]
Affiliation(s)
- Ariela K Holmer
- Inflammatory Bowel Disease Center, Division of Gastroenterology, NYU Langone Health, 240 East 38Th Street, 23Rd Floor, New York, NY, 10016, USA
| | - David Hudesman
- Inflammatory Bowel Disease Center, Division of Gastroenterology, NYU Langone Health, 240 East 38Th Street, 23Rd Floor, New York, NY, 10016, USA.
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White I, Karki C, Geransar P, Leisle L, Junker S, Fleshner P. Impact of Seton Use on Clinical, Patient-Reported, and Healthcare Resource Utilization Outcomes in Complex Crohn's Perianal Fistulas: A Systematic Literature Review. Inflamm Bowel Dis 2024:izae186. [PMID: 39298676 DOI: 10.1093/ibd/izae186] [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: 01/31/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Optimal treatment strategies for seton use in patients with Crohn's perianal fistulas (CPF) remain elusive. This systematic literature review aimed to summarize clinical, patient-reported, and healthcare resource utilization (HCRU) outcomes associated with seton use for symptomatic relief and treatment of complex CPF. METHODS Electronic databases (MEDLINE, Embase, EBM Reviews, EconLit) were searched. Titles, abstracts, and relevant full texts were screened by 2 reviewers for inclusion using prespecified PICOS-T criteria. Articles published in English between January 1, 1980 and September 6, 2021 were included; animal/in vitro studies and case reports with <5 patients were excluded. Outcomes of interest included rates of complete response/remission and fistula recurrence in patients receiving seton with/without infliximab or biologics. Data were summarized using descriptive statistics. RESULTS Overall, 56 studies were included (full texts: n = 43; congress abstracts: n = 13). CPF and clinical outcome definitions were heterogeneous. Rates (range) of complete response/remission varied widely (seton: 13%-75%; seton + infliximab: 23%-100%; seton + biologics: 23%-59%) as did rates for fistula recurrence (seton: 4%-68%; seton + infliximab: 0%-50%; seton + biologics: 0%-17%). Rates of fistula-related reintervention, new fistula or abscess formation, and abscess recurrence were also varied; more consistency was observed regarding the use of patient-reported outcomes. Few studies reported outcomes from pediatric/adolescent patients or HCRU. CONCLUSIONS Optimal use of seton in patients with CPF remains unclear. International standardization of definitions for CPF and related clinical outcomes are required to permit data comparability and identify the most effective treatment strategies involving seton use in CPF.
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Affiliation(s)
- Ian White
- Department of Surgery, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Chitra Karki
- Takeda Pharmaceuticals USA, Inc., Cambridge, MA, USA
| | - Parnia Geransar
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | - Lilia Leisle
- Ingress-Health HWM GmbH, an affiliate of Cytel, Inc., Real World & Advanced Analytics, Berlin, Germany
| | - Sophia Junker
- Ingress-Health HWM GmbH, an affiliate of Cytel, Inc., Real World & Advanced Analytics, Berlin, Germany
| | - Phillip Fleshner
- Cedars-Sinai Medical Center, Division of Colon and Rectal Surgery, Los Angeles, CA, USA
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9
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Singh A, Midha V, Kochhar GS, Shen B, Sood A. Management of Perianal Fistulizing Crohn's Disease. Inflamm Bowel Dis 2024; 30:1579-1603. [PMID: 37672347 DOI: 10.1093/ibd/izad195] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Indexed: 09/08/2023]
Abstract
Perianal fistulizing Crohn's disease (CD) represents a severe phenotype of CD that is associated with significant morbidity and reduction in quality of life. Perianal fistulizing CD is caused by a complex interplay of genetic predisposition, immune dysregulation, gut dysbiosis, and various unknown physiological and mechanical factors. A multidisciplinary approach is hence required for optimal management . A detailed anatomical description and classification of perianal fistula, including comprehensive clinical, endoscopic, and radiological diagnostic workup, is an important prerequisite to treatment. For simple perianal fistulas, use of antibiotics and immunomodulators, with or without fistulotomy, are appropriate measures. The medical management of complex perianal fistula, on the other hand, requires adequate control of infection before initiation of therapy with immunomodulators. In active complex perianal fistula, anti-tumor necrosis factors remain the most accepted therapy, with concomitant use of antibiotics or immunomodulators enhancing the efficacy. For patients refractory to anti-tumor necrosis factors, treatment with anti-integrins, anti-interleukins, and small molecules is being evaluated. Mesenchymal stem cells, hyperbaric oxygen therapy, and exclusive enteral nutrition have also been investigated as adjunct therapies. Despite the expansion of the medical armamentarium, a large proportion of the patients require surgical interventions. In this review, we provide an up-to-date overview of the pathophysiology, clinical presentation, diagnosis, and medical management of perianal fistulizing CD. A brief overview of the surgical management of perianal fistulizing CD is also provided.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, India
| | - Gursimran Singh Kochhar
- Division of Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Bo Shen
- Center for Interventional Inflammatory Bowel Disease, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center, New York, NY, USA
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, India
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10
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Fung M, Farbod Y, Kankouni H, Singh S, McCurdy JD. Does Combined Medical and Surgical Treatment Improve Perianal Fistula Outcomes in Patients With Crohn's Disease? A Systematic Review and Meta-Analysis. J Crohns Colitis 2024; 18:1261-1269. [PMID: 38491943 PMCID: PMC11324341 DOI: 10.1093/ecco-jcc/jjae035] [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: 02/02/2024] [Accepted: 03/15/2024] [Indexed: 03/18/2024]
Abstract
BACKGROUND The optimal treatment of perianal fistulizing Crohn's disease [PFCD] is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-tumour necrosis factor [anti-TNF] therapy [combined therapy] vs either therapy alone. METHODS MEDLINE, EMBASE, and Cochrane databases were searched systematically up to end December 2023. Surgical intervention was defined as an exam under anaesthesia ± setons. We calculated weighted risk ratios [RRs] with 95% confidence intervals [CIs] for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively. RESULTS Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention, and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response [RR 1.10; 95% CI 0.93-1.30, p = 0.28] and healing [RR 1.06; 95% CI 0.86-1.31, p = 0.58] was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response [RR 1.25; 95% CI 1.10-1.41, p < 0.001] and healing [RR 1.17; 95% CI 1.00-1.36, p = 0.05] compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures. CONCLUSION Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings.
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Affiliation(s)
- Moses Fung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Yasamin Farbod
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Husain Kankouni
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Jeffrey D McCurdy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute, Ottawa, Ontario, USA
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11
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Hanna LN, Anandabaskaran S, Iqbal N, Geldof J, LeBlanc JF, Dige A, Lundby L, Vermeire S, D'Hoore A, Verstockt B, Bislenghi G, De Looze D, Lobaton T, Van de Putte D, Spinelli A, Carvello M, Danese S, Buskens CJ, Gecse K, Hompes R, Becker M, van der Bilt J, Bemelman W, Sebastian S, Moran G, Lightner AL, Wong SY, Colombel JF, Cohen BL, Holubar SD, Ding NS, Behrenbruch C, Sahnan K, Misra R, Lung P, Hart A, Tozer P. Perianal Fistulizing Crohn's Disease: Utilizing the TOpClass Classification in Clinical Practice to Provide Targeted Individualized Care. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00692-X. [PMID: 39134293 DOI: 10.1016/j.cgh.2024.06.047] [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: 02/08/2024] [Revised: 04/26/2024] [Accepted: 06/11/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND & AIMS Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice. METHODS An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, inflammatory bowel disease surgeons, and radiologists specialized in PFCD. The process was informed by the multi-disciplinary team management of 8 high-volume fistula centres in North America, Europe, and Australia. RESULTS The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimization of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group. CONCLUSION This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient goal-centered approach to medical and surgical management options for individual patients with PFCD.
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Affiliation(s)
- Luke N Hanna
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; IBD Unit, St Mark's Hospital, London, United Kingdom.
| | - Sulak Anandabaskaran
- Department of Gastroenterology, School of Clinical Medicine, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, Australia
| | - Nusrat Iqbal
- Department of Colorectal Surgery, St Mark's Hospital, London, United Kingdom
| | - Jeroen Geldof
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
| | - Jean-Frédéric LeBlanc
- Department of Gastroenterology, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
| | - Anders Dige
- Department of Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Lilli Lundby
- Department of Surgery, Pelvic Floor Unit, Aarhus University Hospital, Aarhus, Denmark
| | - Séverine Vermeire
- Department of Gastroenterology, University Hospitals of Leuven, Leuven, Belgium
| | - André D'Hoore
- Department of Abdominal Surgery, University Hospitals of Leuven, Leuven, Belgium
| | - Bram Verstockt
- Department of Gastroenterology, University Hospitals of Leuven, Leuven, Belgium
| | - Gabriele Bislenghi
- Department of Abdominal Surgery, University Hospitals of Leuven, Leuven, Belgium
| | - Danny De Looze
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
| | - Triana Lobaton
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
| | - Dirk Van de Putte
- Department of Colorectal Surgery, University Hospital Ghent, Ghent, Belgium
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Michele Carvello
- Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Silvio Danese
- IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Christianne J Buskens
- Department of Colorectal Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Krisztina Gecse
- Department of Gastroenterology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Roel Hompes
- Department of Colorectal Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Marte Becker
- Department of Gastroenterology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Jarmila van der Bilt
- Department of Colorectal Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Willem Bemelman
- Department of Colorectal Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Shaji Sebastian
- IBD Unit, Hull University Teaching Hospitals, Hull, United Kingdom
| | - Gordan Moran
- Department of Gastroenterology, Nottingham University Hospitals, Nottingham, United Kingdom
| | - Amy L Lightner
- Department of Colorectal Surgery, Scripps Clinic, San Diego, California
| | - Serre-Yu Wong
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jean-Frédéric Colombel
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Benjamin L Cohen
- Department of Gastroenterology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Stefan D Holubar
- Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Nik S Ding
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | - Corina Behrenbruch
- Department of Colorectal Surgery, St Vincent's Hospital, Melbourne, Australia
| | - Kapil Sahnan
- Department of Colorectal Surgery, St Mark's Hospital, London, United Kingdom
| | - Ravi Misra
- IBD Unit, St Mark's Hospital, London, United Kingdom
| | - Phillip Lung
- Department of Radiology, St Mark's Hospital, London, United Kingdom
| | - Ailsa Hart
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; IBD Unit, St Mark's Hospital, London, United Kingdom
| | - Phil Tozer
- Department of Colorectal Surgery, St Mark's Hospital, London, United Kingdom
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12
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Richard N, Derinck A, Bridoux V, Charpentier C, Savoye Collet C, Savoye G. Which magnetic resonance imaging feature is associated with treatment response in perianal fistulizing Crohn's disease? Abdom Radiol (NY) 2024; 49:2913-2920. [PMID: 38512515 DOI: 10.1007/s00261-024-04238-3] [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: 12/10/2023] [Revised: 01/31/2024] [Accepted: 02/05/2024] [Indexed: 03/23/2024]
Abstract
PURPOSE Perianal fistulae are disabling complications of Crohn's Disease. Magnetic resonance imaging features could predict treatment response. This study aimed to determine which magnetic resonance imaging features were predictive of long-term clinical outcome in real life. METHODS Consecutive patients with magnetic resonance imaging performed in a tertiary center were retrospectively analyzed. Clinical outcome was defined as a need for surgical drainage of perianal fistulae or hospitalization. Clinical data and magnetic resonance imaging features (MAGNIFI-CD and Van Assche indices, degree of fibrosis) were studied. RESULTS Fifty-two patients were included between 2016 and 2019 with a mean follow-up of 38 months [29;48]. A higher MAGNIFI-CD index (17/25 versus 11/25; p < 0.01) was associated with an unfavorable long-term clinical outcome. The MAGNIFI-CD index showed an area under the curve of 0.74 (p = 0.006) to predict the clinical outcome of perianal Crohn's disease, compared to 0.67 (p < 0.05) for the Van Assche index. At a threshold of 13 for the MAGNIFI-CD index, sensitivity was 75% (CI95% [59%; 86%]) and specificity was 69% (CI95% [44%; 86%]). No association was found between the degree of fibrosis and clinical outcome, but the association of a high degree of fibrosis (≥ 80%) and of a low MAGNIFI-CD index (≤ 13) was predictive of clinical outcome (p < 0.01). CONCLUSION The MAGNIFI-CD index could be used to predict clinical outcome in perianal Crohn's disease. In combination with a high degree of fibrosis, a low MAGNIFI-CD index, may help to identify patients with the best prognosis.
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Affiliation(s)
- Nicolas Richard
- Department of Gastroenterology, CHU Rouen, INSERM, ADEN UMR1073, Nutrition, Inflammation and microbiota-gut-brain axis, Univ Rouen Normandie, 76000, Rouen, France.
| | | | - Valérie Bridoux
- Department of Digestive Surgery, CHU Rouen, 76000, Rouen, France
| | | | - Céline Savoye Collet
- Department of Radiology, CHU Rouen, QUANTIF-LITIS EA 4108, Univ Rouen Normandie, 76000, Rouen, France
| | - Guillaume Savoye
- Department of Gastroenterology, CHU Rouen, INSERM, ADEN UMR1073, Nutrition, Inflammation and microbiota-gut-brain axis, Univ Rouen Normandie, 76000, Rouen, France
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13
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Prasad S, Cross RK, Monroe MB, Dolinger MT, Motte R, Hong S, Stidham RW, Kumar N, Levine D, Larijani A, Simone A, Chachu KA, Wyborski R, Heller CA, Moss AC, Schwerbrock NMJ, Selaru FM. Challenges in IBD Research 2024: Novel Technologies. Inflamm Bowel Dis 2024; 30:S30-S38. [PMID: 38778625 DOI: 10.1093/ibd/izae082] [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: 03/13/2024] [Indexed: 05/25/2024]
Abstract
Novel technology is one of the five focus areas of the Challenges in Inflammatory Bowel Disease (IBD) Research 2024 document. Building off the Challenges in IBD Research 2019 document, the Foundation aims to provide a comprehensive overview of current gaps in IBD research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of a multidisciplinary collaboration from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization. Specifically, the Novel Technologies section focuses on addressing key research gaps to enable interception and improve remission rates in IBD. This includes testing predictions of disease onset and progression, developing novel technologies tailored to specific phenotypes, and facilitating collaborative translation of science into diagnostics, devices, and therapeutics. Proposed priority actions outlined in the document include real-time measurement of biological changes preceding disease onset, more effective quantification of fibrosis, exploration of technologies for local treatment of fistulas, and the development of drug delivery platforms for precise, location-restricted therapies. Additionally, there is a strong emphasis on fostering collaboration between various stakeholders to accelerate progress in IBD research and treatment. Addressing these research gaps necessitates the exploration and implementation of bio-engineered novel technologies spanning a spectrum from materials to systems. By harnessing innovative ideas and technologies, there's a collective effort to enhance patient care and outcomes for individuals affected by IBD.
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Affiliation(s)
- Shalini Prasad
- Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA
| | - Raymond K Cross
- Director of the Inflammatory Bowel Disease Program, University of Maryland School of Medicine, Maryland, MD, USA
| | - Mary Beth Monroe
- Department of Biomedical and Chemical Engineering BioInspired Syracuse: Institute for Material and Living Systems, Syracuse University, Syracuse, NY, USA
| | - Michael T Dolinger
- Icahn School of Medicine at Mount Sinai, Division of Pediatric Gastroenterology, New York, NY, USA
| | - Rachel Motte
- TISSIUM, 74 Rue du Faubourg Saint-Antoine, Paris, France
| | - Sungmo Hong
- Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA
| | - Ryan W Stidham
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA
| | - Narendra Kumar
- Department of Pharmaceutical Science, ILR-College of Pharmacy, Texas A&M University, TX, USA
| | - Deborah Levine
- Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA
| | - Anthony Larijani
- Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA
| | - Ashley Simone
- Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA
| | - Karen A Chachu
- Department of Medicine, Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | | | - Caren A Heller
- Members of the Crohn's & Colitis Foundation, New York, NY, USA
| | - Alan C Moss
- Members of the Crohn's & Colitis Foundation, New York, NY, USA
| | | | - Florin M Selaru
- Division of Gastroenterology, Oncology and Biomedical Engineering, Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA
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14
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Vuyyuru SK, Solitano V, Narula N, Lee MJ, MacDonald JK, McCurdy JD, Singh S, Ma C, Jairath V. Pharmacological Therapies for the Management of Fistulizing Crohn's Disease: A Systematic Review and Meta-Analysis. J Crohns Colitis 2024; 18:589-603. [PMID: 37933849 DOI: 10.1093/ecco-jcc/jjad185] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Indexed: 11/08/2023]
Abstract
BACKGROUND Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD. METHODS MEDLINE, Embase, and CENTRAL were searched on May 26, 2022, for randomized controlled trials [RCTs] of pharmacological therapy in adults with fistulizing CD. The primary outcome was induction and maintenance of fistula response. Pooled risk ratios [RRs] and 95% confidence intervals [CIs] were calculated. GRADE was used to assess the certainty of evidence. RESULTS Thirty-eight RCTs were included. Nineteen trials [50%] exclusively involved perianal fistula. The remaining studies included some participants with non-perianal fistula. Pooled RRs for anti-tumour necrosis factor [TNF] agents were not statistically significant for induction [RR 1.36, 95% CI 0.97-1.91] or maintenance of fistula response [RR 1.48, 95% CI 0.97-2.27]. However, in a sensitivity analysis of studies with fistula response as the primary outcome, anti-TNFs were superior to placebo for induction [RR 1.94, 95% CI 1.10-3.41] and maintenance [RR 1.88, 95% CI 1.23-2.88] of fistula response. Oral small molecules [RR 2.56, 95% CI 1.18-5.53] and mesenchymal stem cell [MSC] therapy [RR 1.26, 95% CI 1.01-1.57] were effective for induction of fistula response. Ustekinumab was associated with maintenance of fistula response [RR 1.80, 95% CI 1.04-3.11]. Vedolizumab was not superior to placebo. The certainty of evidence ranged from very low to moderate. CONCLUSION Very low- to moderate-certainty evidence suggests that anti-TNF therapy, oral small molecules, ustekinumab, and MSCs are effective for perianal fistulizing CD. Dedicated fistula studies evaluating biologics and small molecules are needed.
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Affiliation(s)
- Sudheer K Vuyyuru
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University, London, ON, Canada
- Alimentiv Inc, London, ON, Canada
| | - Virginia Solitano
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University, London, ON, Canada
- Alimentiv Inc, London, ON, Canada
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Neeraj Narula
- Department of Medicine, Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Matthew J Lee
- Department of Oncology and Metabolism, The Medical School, University of Sheffield, Beech Hill Road, Sheffield, UK
| | | | - Jeffrey D McCurdy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Christopher Ma
- Alimentiv Inc, London, ON, Canada
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University, London, ON, Canada
- Alimentiv Inc, London, ON, Canada
- Department of Epidemiology and Biostatistics, Western University, London, ON, Canada
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15
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Gadepalli SK, Adler J. Perianal disease: Updates and controversies in closing the gaps. Semin Pediatr Surg 2024; 33:151402. [PMID: 38603820 DOI: 10.1016/j.sempedsurg.2024.151402] [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: 04/13/2024]
Abstract
Perianal complications are common and morbid in children with Crohn's disease. In this review, we describe the epidemiology, the presentation and diagnosis, evaluation and management. We focus on updates such as the increasing frequency of biologic medications and MRI for evaluation. We also highlight controversies on the timing and approaches to surgical techniques. Finally, perianal disease requires the coordination of multidisciplinary care with nursing, radiology, gastroenterology, and surgery to optimize outcomes - both medical and patient-centered.
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Affiliation(s)
- Samir K Gadepalli
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, United States; Susan G. Meister CHEAR Center, University of Michigan, Ann Arbor, MI, United States.
| | - Jeremy Adler
- Susan G. Meister CHEAR Center, University of Michigan, Ann Arbor, MI, United States; Division of Pediatric Gastroenterology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
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16
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Park MY, Yoon YS, Park JH, Lee JL, Yu CS. Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn's disease. World J Stem Cells 2024; 16:257-266. [PMID: 38577230 PMCID: PMC10989284 DOI: 10.4252/wjsc.v16.i3.257] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 12/25/2023] [Accepted: 02/18/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn's disease (CD). Anti-tumor necrotic factor (TNF) therapy combined with drainage procedure is effective as well. However, previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure. AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn's perianal fistula (CPF) closure rates after stem cell transplantation with and without anti-TNF therapy, and to identify the factors affecting CPF closure and recurrence. METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled. Clinical data were compared according to anti-TNF therapy and CPF closure. RESULTS A total of 65 patients were included. The median age of females was 26 years (range: 21-31) and that of males was 29 (44.6%). The mean follow-up duration was 65.88 ± 32.65 months, and complete closure was observed in 50 (76.9%) patients. The closure rates were similar after stem cell transplantation with and without anti-TNF therapy (66.7% vs 81.6% at 3 year, P = 0.098). The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture (P = 0.027, 0.002, and 0.008, respectively). Clinical factors such as complexity, number of fistulas, presence of concurrent abscess, and medication were not significant for closure. The cumulative 1-, 2-, and 3-year closure rates were 66.2%, 73.8%, and 75.4%, respectively. CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation. However, both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy. Fistulous tract length, proctitis, and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.
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Affiliation(s)
- Min Young Park
- Division of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
| | - Jae Ha Park
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
| | - Jong Lyul Lee
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
| | - Chang Sik Yu
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
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17
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Khan SZ, Arline A, Williams KM, Lee MJ, Steinhagen E, Stein SL. The use of core descriptors from the ENiGMA code study in recent literature: a systematic review. Colorectal Dis 2024; 26:428-438. [PMID: 38296841 DOI: 10.1111/codi.16893] [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: 06/08/2023] [Accepted: 01/10/2024] [Indexed: 02/02/2024]
Abstract
AIM The heterogeneity in data quality presented in studies regarding Crohn's anal fistula (CAF) limit extrapolation into clinical practice. The ENiGMA collaborators established a core descriptor set to standardize reporting of CAF. The aim of this work was to quantify the use of these descriptors in recent literature. METHOD We completed a systematic review of PubMed and the Cochrane Library, extracting publications from the past 10 years specific to the clinical interventions and outcomes of CAF, and reported in line with PRISMA guidance. Each article was assessed for inclusion of ENiGMA descriptors. The median number of descriptors per publication was evaluated along with the overall frequency of each individual descriptor. Use of ENiGMA descriptors was compared between medical and procedural publications. RESULTS Ninety publications were included. The median number of descriptors was 15 of 37; 16 descriptors were used in over half of the publications while 17 were used in fewer than a third. Descriptors were more frequently used in procedural (n = 16) than medical publications (n = 14) (p = 0.031). In procedural publications, eight descriptors were more frequently used including Faecal incontinence, Number of previous fistula interventions, Presence and severity of anorectal stenosis and Current proctitis. Medical publications were more likely to include Previous response to biological therapy and Duration and type of current course of biological therapy. CONCLUSION With many descriptors being used infrequently and variations between medical and procedural literature, the colorectal community should assess the need for all 37 descriptors.
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Affiliation(s)
- Saher-Zahra Khan
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
| | - Andrea Arline
- Case Western Reserve University School of Medicine, Cleveland, USA
| | | | - Matthew J Lee
- Academic Directorate of General Surgery, Sheffield Teaching Hospitals NHS FT, Sheffield, UK
- Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK
| | - Emily Steinhagen
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
| | - Sharon L Stein
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
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18
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Cheng F. Comments on: "A Phase IB/IIA Study of Ex Vivo Expanded Allogeneic Bone-Marrow Derived Mesenchymal Stem Cells for the Treatment of Perianal Fistulizing Crohn's Disease". Dis Colon Rectum 2024; 67:e202. [PMID: 38063466 DOI: 10.1097/dcr.0000000000003176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Affiliation(s)
- Fang Cheng
- Division of Gastroenterology, Zigong First People's Hospital, Sichuan Province, China
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19
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Devi J, Ballard DH, Aswani-Omprakash T, Parian AM, Deepak P. Perianal fistulizing Crohn's disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies. Indian J Gastroenterol 2024; 43:48-63. [PMID: 38308773 DOI: 10.1007/s12664-024-01524-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/02/2024] [Indexed: 02/05/2024]
Abstract
Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe phenotypes. Characterized by fistula formation and abscesses, CD-PAF impacts 17% to 34% of all CD cases and with a significantly deleterious impact on patient's quality of life, while increasing the risk for anorectal cancers. The pathogenesis involves a complex interplay of genetic, immunological and environmental factors, with cytokines such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) playing pivotal roles. Diagnostic protocols require a multi-disciplinary approach including colonoscopy, examination under anesthesia and magnetic resonance imaging. In terms of treatment, biologics alone often prove inadequate, making surgical interventions such as setons and fistula surgeries essential. Emerging therapies such as mesenchymal stem cells are under study. The South Asian context adds layers of complexity, including diagnostic ambiguities related to high tuberculosis prevalence, healthcare access limitations and cultural stigma toward perianal Crohn's disease and ostomy surgery. Effective management necessitates an integrated, multi-disciplinary approach, especially in resource-constrained settings. Despite advances, there remain significant gaps in understanding the disease's pathophysiology and a dearth of standardized outcome measures, underscoring the urgent need for comprehensive research.
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Affiliation(s)
- Jalpa Devi
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine in Saint Louis, 660 S. Euclid Avenue, Campus Box 8124, Saint Louis, MO, 63110, USA
| | - David H Ballard
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | | | - Alyssa M Parian
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Parakkal Deepak
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine in Saint Louis, 660 S. Euclid Avenue, Campus Box 8124, Saint Louis, MO, 63110, USA.
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20
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White I, Yanai H, Avni I, Slavin M, Naftali T, Tovi S, Dotan I, Wasserberg N. Mesenchymal stem cell therapy for Crohn's perianal fistula-a real-world experience. Colorectal Dis 2024; 26:102-109. [PMID: 38095303 DOI: 10.1111/codi.16830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 04/11/2023] [Accepted: 09/05/2023] [Indexed: 01/28/2024]
Abstract
AIM Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment. METHODS All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented. RESULTS Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events. CONCLUSION In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.
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Affiliation(s)
- Ian White
- Colorectal Unit, Division of Surgery, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Henit Yanai
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Irit Avni
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Moran Slavin
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Surgery B Department, Meir Medical Center, Kfar Saba, Israel
| | - Timna Naftali
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Gastroenterology Department, Meir Medical Center, Kfar Saba, Israel
| | - Shifra Tovi
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Iris Dotan
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Nir Wasserberg
- Colorectal Unit, Division of Surgery, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Maas L, Gao R, Cusumano V, Spartz E, Chowdhury R, Krishna M, Lazarev M, Melia J, Selaru F, Sharma S, Limketkai B, Parian A. Superior Efficacy of Infliximab Versus Adalimumab for First-Line Treatment of Crohn's Perianal Fistulae. Dig Dis Sci 2023; 68:3994-4000. [PMID: 37540392 DOI: 10.1007/s10620-023-08060-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 07/26/2023] [Indexed: 08/05/2023]
Abstract
BACKGROUND Crohn's disease perianal fistulae (CD-PAF) occur in 25% of patients and are notoriously challenging to manage. Tumor necrosis factor inhibitors are first line agents. AIMS The aim of this study was to compare infliximab (IFX) versus adalimumab (ADA) efficacy in CD-PAF healing over time. METHODS A retrospective study at two large-tertiary medical centers was performed. Inclusion criteria were actively draining CD-PAF and initial treatment with IFX or ADA following CD-PAF diagnosis. The primary endpoints were perianal fistula response and remission at 6 and 12 months. Secondary endpoints included biologic persistence over time and dose escalation at 6 and 12 months. RESULTS Among 151 patients included in the study, 92 received IFX and 59 received ADA as first line agents after CD-PAF diagnosis. At 6 months, the 64.9% of the IFX group and 34.8% of the ADA group demonstrated CD-PAF clinical improvement (p < 0.01). Univariate and multivariate analyses demonstrated significant differences among the IFX and ADA groups for clinical response at 6-months and 12-months (p = 0.002 and p = 0.042, respectively). There were no factors that predicted response, with the exception of concomitant immunomodulator affecting the 6-month clinical response (p = 0.021). Biologic persistence, characterized by Kaplan Meier methods, was significantly longer in the IFX group compared to the ADA group (Log-rank p = 0.01). CONCLUSION IFX induction and maintenance is associated with higher rates of response and remission in CD-PAF healing as well as higher treatment persistence compared to ADA. Additionally, our study supports the use of concomitant immunomodulator therapy for CD-PAF healing and remission.
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Affiliation(s)
- Laura Maas
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA.
| | - Ruiyi Gao
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA
| | - Vivy Cusumano
- Division of Digestive Diseases, Center for Inflammatory Bowel Diseases, Vatche & Tamar Manoukian, UCLA School of Medicine, Los Angeles, CA, USA
| | - Ellen Spartz
- Division of Digestive Diseases, Center for Inflammatory Bowel Diseases, Vatche & Tamar Manoukian, UCLA School of Medicine, Los Angeles, CA, USA
| | - Reezwana Chowdhury
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA
| | - Mahesh Krishna
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA
| | - Mark Lazarev
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA
| | - Joanna Melia
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA
| | - Florin Selaru
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA
| | - Sowmya Sharma
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA
| | - Berkeley Limketkai
- Division of Digestive Diseases, Center for Inflammatory Bowel Diseases, Vatche & Tamar Manoukian, UCLA School of Medicine, Los Angeles, CA, USA
| | - Alyssa Parian
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD, 21224, USA
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22
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Gubatan J, Frost S, Levitte S, Keyashian K. Rates and Predictors of Long-term Clinical Outcomes in Patients With Perianal Crohn's Disease on Biologic Therapy. J Clin Gastroenterol 2023; 57:617-623. [PMID: 35703262 DOI: 10.1097/mcg.0000000000001729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 05/15/2022] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND GOALS Perianal Crohn's disease (pCD) represents an aggressive phenotype with limited studies on long-term outcomes. We evaluated 5-year outcomes of these patients on biologic therapies. METHODS We performed a retrospective analysis of patients with pCD at a tertiary medical center. We used Kaplan-Meier curves to estimate rates and multivariate logistic regression to identify predictors of long-term outcomes. RESULTS We included 311 patients with pCD of which 168 patients were started on biologics [138 anti-tumor necrosis factor (TNF) α, 14 vedolizumab, 16 ustekinumab] at the time of diagnosis. Anti-TNF use at the time of diagnosis was associated with decreased rates of perianal abscess recurrence [hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.32-0.74], whereas ustekinumab use was associated with increased rates of perianal fistula closure (HR=3.58, 95% CI: 1.04-12.35) and decreased rates of perianal abscess recurrence (HR=0.20, 95% CI: 0.07-0.56) at follow-up. Among patients who failed their first anti-TNF, switching to another anti-TNF was associated with decreased rates of colectomy (HR=0.20, 95% CI: 0.04-0.90) and permanent diversion (HR=0.16, 95% CI: 0.03-0.94) compared with ustekinumab, whereas vedolizumab use was associated with decreased perianal fistula closure (HR=0.22, 95% CI: 0.05-0.96) compared with ustekinumab. Predictors of colectomy included colonic disease (odds ratio=2.71, 95% CI: 1.36-5.38) and anal stenosis (odds ratio=4.44, 95% CI: 1.59-12.43). CONCLUSION Type of biologic use at the time of pCD diagnosis or after first anti-TNF failure may be associated with long-term outcomes in patients with pCD.
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Affiliation(s)
| | | | - Steven Levitte
- Division of Pediatric Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA
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23
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Weng MT, Lin KL, Huang YL, Karki C, Hong JL, Bennett D, Arnold Chan K, Wei SC. Epidemiology, Disease Course, and Clinical Outcomes of Perianal Fistulas and Fissures Crohn's Disease: A Nationwide Population-Based Study in Taiwan. CROHN'S & COLITIS 360 2023; 5:otad035. [PMID: 37497019 PMCID: PMC10368329 DOI: 10.1093/crocol/otad035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Indexed: 07/28/2023] Open
Abstract
Background Population-based data on the course of perianal disease in East Asian populations with Crohn's disease (CD) are limited. This study examined the prevalence, clinical course, and compared the outcomes of CD patients with perianal CD (pCD) versus without pCD in Taiwan. Methods A nationwide population-based study was implemented from 2000 to 2017 by using the Taiwan National Health Insurance Research Database. Results Of 2424 patients with CD, 358 (14.8%) patients with pCD were identified. Most patients with CD and pCD were men (79.3%). The mean age at CD diagnosis was lower in patients with pCD (33.7 years) than in those without pCD (44.9 years). Approximately half the patients with pCD received the pCD diagnosis at least 6 months before receiving a CD diagnosis. Approximately one-third (121/358) of patients with pCD had recurrent fistula; the median recurrence interval was 239 days. Compared with patients without pCD, patients with pCD had higher mean incidences of hospitalization (7.0 vs 3.8, P < .01), outpatient visits (13 vs 2.9, P < .01), and emergency room visits (10.3 vs 4.4, P < .01) over a 15-year period. Although patients with pCD had higher rates of healthcare utilization, their 15-year mortality rate was lower than that of those without pCD (6.1% vs 17.3%, P < .01). Conclusions The period prevalence of pCD in Taiwanese patients with CD was 14.8%. Although patients with pCD required more intensive care and had greater healthcare utilization, they did not have inferior survival outcomes compared with those without pCD.
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Affiliation(s)
- Meng-Tzu Weng
- Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, HsinChu, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Kuan-Lin Lin
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
| | - Ya-Ling Huang
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
| | - Chitra Karki
- Global Evidence and Outcomes, Takeda Development Center Americas, Inc., Cambridge, MA, USA
| | - Jin-Liern Hong
- Global Evidence and Outcomes, Takeda Development Center Americas, Inc., Cambridge, MA, USA
| | - Dimitri Bennett
- Global Evidence and Outcomes, Takeda Development Center Americas, Inc., Cambridge, MA, USA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - K Arnold Chan
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
| | - Shu-Chen Wei
- Address correspondence to: Shu-Chen Wei, MD, PhD, Division of Hepatology and Gastroenterology, Department of Internal Medicine, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City 100, Taiwan; or, No. 7 Chung-Shan South Road, Taipei, Taiwan ()
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24
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Shehab M, Alrashed F, Heron V, Restellini S, Bessissow T. Comparative Efficacy of Biologic Therapies for Inducing Response and Remission in Fistulizing Crohn's Disease: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Inflamm Bowel Dis 2023; 29:367-375. [PMID: 35604382 DOI: 10.1093/ibd/izac103] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND The medical treatment of fistulizing Crohn's disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD. METHODS We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55). CONCLUSIONS Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.
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Affiliation(s)
- Mohammad Shehab
- Division of Gastroenterology, Department of Internal Medicine, Mubarak Alkabeer University Hospital, Aljabreyah, Kuwait
| | - Fatema Alrashed
- Department of Public Health, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA
- Department of Pharmacy Practice, Faculty of Pharmacy, Health Science Center, Kuwait University, Jabirya, Kuwait
| | - Valérie Heron
- Department of Gastroenterology, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
| | - Sophie Restellini
- Division of Qastroenterology, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland
| | - Talat Bessissow
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, Montreal, Quebec, Canada
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25
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Laland M, François M, D'Amico F, Zallot C, Brochard C, Dewitte M, Siproudhis L, Peyrin-Biroulet L, Bouguen G. Identification of the optimal medical and surgical management for patients with perianal fistulising Crohn's disease. Colorectal Dis 2023; 25:75-82. [PMID: 36016511 DOI: 10.1111/codi.16314] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 06/28/2022] [Accepted: 08/08/2022] [Indexed: 02/02/2023]
Abstract
AIM The aim of our study was to assess the best medical and surgical approaches for perianal Crohn's disease (PCD) in order to identify an optimal combined medical and surgical treatment. METHODS Medical records of all patients with PCD treated with TNFα antagonists in two referral centres between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model. RESULTS A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. A combination of TNFα antagonist with an immunosuppressant and the presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within 1 year was the best management for PCD patients (p = 0.02). CONCLUSION Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within 1 year is the best management for PCD patients.
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Affiliation(s)
| | | | - Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Camille Zallot
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Charlène Brochard
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), Rennes, France
| | - Marie Dewitte
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Rennes, France
| | - Laurent Siproudhis
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), Rennes, France
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Guillaume Bouguen
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), Rennes, France
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26
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Badla O, Goit R, Saddik SE, Dawood S, Rabih AM, Mohammed A, Raman A, Uprety M, Calero M, Villanueva MRB, Joshaghani N, Villa N, Mohammed L. The Multidisciplinary Management of Perianal Fistulas in Crohn’s Disease: A Systematic Review. Cureus 2022; 14:e29347. [PMID: 36284816 PMCID: PMC9582904 DOI: 10.7759/cureus.29347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 09/19/2022] [Indexed: 11/05/2022] Open
Abstract
Perianal fistulas in Crohn's disease (CD) are often recurring and challenging to treat. This systematic review aimed to evaluate the medical, surgical, and combination treatment options and provide an overview of their efficacy. We performed this systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Our group searched PubMed, Medline, PubMed Central, Google Scholar, and ScienceDirect for articles within the last ten years using different terms and criteria mentioned in detail in the search strategy and eligibility criteria sections. Initially, 739 records were retrieved, out of which we excluded 731 records for various reasons, such as irrelevant titles and abstracts and low scores on quality assessment tools. The evidence for combination (surgical and medical) therapy is superior to that for medical and surgical treatments individually. In contrast, the studies on medical and surgical treatments individually reported varied evidence and efficacy for their respective options.
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27
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Bouchard D, Pigot F, de Parades V, Staumont G, Abramowitz L, Siproudhis L, Bouchard D, Pigot F, de Parades V, Staumont G, Abramowitz L, Siproudhis L, Tracanelli L, Fathallah N, Babin-Pigot E, Ferry M, Bouguen G, Laharie D, Cotte E, Panis Y, Peyrin-Biroulet L, Roblin X, Zerbib P. Management of perianal fistulas in Crohn’s disease: a 2021 update of the French National Society of Coloproctology consensus. Tech Coloproctol 2022; 26:805-811. [DOI: 10.1007/s10151-022-02678-x] [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: 10/19/2021] [Accepted: 07/29/2022] [Indexed: 11/28/2022]
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Fehily SR, Al‐Ani AH, Abdelmalak J, Rentch C, Zhang E, Denholm JT, Johnson D, Ng SC, Sharma V, Rubin DT, Gibson PR, Christensen B. Review article: latent tuberculosis in patients with inflammatory bowel diseases receiving immunosuppression-risks, screening, diagnosis and management. Aliment Pharmacol Ther 2022; 56:6-27. [PMID: 35596242 PMCID: PMC9325436 DOI: 10.1111/apt.16952] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 04/14/2022] [Accepted: 04/18/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND One quarter of the world's population has latent tuberculosis infection (LTBI). Systemic immunosuppression is a risk factor for LTBI reactivation and the development of active tuberculosis. Such reactivation carries a risk of significant morbidity and mortality. Despite the increasing global incidence of inflammatory bowel disease (IBD) and the use of immune-based therapies, current guidelines on the testing and treatment of LTBI in patients with IBD are haphazard with a paucity of evidence. AIM To review the screening, diagnostic practices and medical management of LTBI in patients with IBD. METHODS Published literature was reviewed, and recommendations for testing and treatment were synthesised by experts in both infectious diseases and IBD. RESULTS Screening for LTBI should be performed proactively and includes assessment of risk factors, an interferon-gamma releasing assay or tuberculin skin test and chest X-ray. LTBI treatment in patients with IBD is scenario-dependent, related to geographical endemicity, travel and other factors. Ideally, LTBI therapy should be used prior to immune suppression but can be applied concurrently where urgent IBD medical treatment is required. Management is best directed by a multidisciplinary team involving gastroenterologists, infectious diseases specialists and pharmacists. Ongoing surveillance is recommended during therapy. Newer LTBI therapies show promise, but medication interactions need to be considered. There are major gaps in evidence, particularly with specific newer therapeutic approaches to IBD. CONCLUSIONS Proactive screening for LTBI is essential in patients with IBD undergoing immune-suppressing therapy and several therapeutic strategies are available. Reporting of real-world experience is essential to refining current management recommendations.
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Affiliation(s)
- Sasha R. Fehily
- Gastroenterology DepartmentSt Vincent's HospitalMelbourneVictoriaAustralia
- Department of MedicineUniversity of MelbourneParkvilleVictoriaAustralia
| | - Aysha H. Al‐Ani
- Department of MedicineUniversity of MelbourneParkvilleVictoriaAustralia
- Gastroenterology DepartmentRoyal Melbourne HospitalParkvilleVictoriaAustralia
| | | | - Clarissa Rentch
- Gastroenterology DepartmentRoyal Melbourne HospitalParkvilleVictoriaAustralia
| | - Eva Zhang
- Gastroenterology DepartmentRoyal Melbourne HospitalParkvilleVictoriaAustralia
| | - Justin T. Denholm
- Department of MedicineUniversity of MelbourneParkvilleVictoriaAustralia
- Infectious Diseases DepartmentRoyal Melbourne HospitalParkvilleVictoriaAustralia
- Victorian Tuberculosis ProgramMelbourneVictoriaAustralia
- Department of Infectious DiseasesDoherty InstituteParkvilleVictoriaAustralia
| | - Douglas Johnson
- Department of MedicineUniversity of MelbourneParkvilleVictoriaAustralia
- Infectious Diseases DepartmentRoyal Melbourne HospitalParkvilleVictoriaAustralia
| | - Siew C. Ng
- Department of Medicine and TherapeuticsInstitute of Digestive Disease, The Chinese University of Hong KongHong Kong SARChina
| | - Vishal Sharma
- Department of GastroenterologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
| | - David T. Rubin
- University of Chicago Medicine Inflammatory Bowel Disease CenterUniversity of Chicago MedicineChicagoIllinoisUSA
| | - Peter R. Gibson
- Department of GastroenterologyMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Britt Christensen
- Department of MedicineUniversity of MelbourneParkvilleVictoriaAustralia
- Gastroenterology DepartmentRoyal Melbourne HospitalParkvilleVictoriaAustralia
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29
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Wetwittayakhlang P, Al Khoury A, Hahn GD, Lakatos PL. The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials. J Clin Med 2022; 11:3045. [PMID: 35683433 PMCID: PMC9181669 DOI: 10.3390/jcm11113045] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/21/2022] [Accepted: 05/25/2022] [Indexed: 02/04/2023] Open
Abstract
Fistulizing Crohn's disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30-50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Alex Al Khoury
- Division of Gastroenterology, University of Florida, Jacksonville, FL 32209, USA;
| | - Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Graduate Course Sciences in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- First Department of Medicine, Semmelweis University, 1085 Budapest, Hungary
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Wood T, Truong A, Mujukian A, Zaghiyan K, Fleshner P. Increasing experience with the LIFT procedure in Crohn's disease patients with complex anal fistula. Tech Coloproctol 2022; 26:205-212. [PMID: 35103901 DOI: 10.1007/s10151-022-02582-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 01/21/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Surgical management of anal fistulas in Crohn's disease (CD) is associated with high failure rates, and treatment options are limited due to ongoing proctitis, multiple tracts, and concern for incontinence and non-healing wounds. The aim of this study was to investigate the healing rate of ligation of the inters-sphincteric fistula tract (LIFT) for anal fistulas in Crohn's disease and identify prognostic factors for healing. METHODS This prospective analysis compared long-term healing rates of CD patients undergoing LIFT for anal fistulas. Consecutive patients with CD who underwent LIFT procedure at our institution, in the period from March 2012 to September 2019 were included. The main outcome was anal fistula healing rate. RESULTS The study cohort of 46 patients (mean age of 34.2 ± 13.0 years, 18 (40%) males). After a mean follow-up time of 33 ± 28 months, fistula healing was seen in 30 (65%) patients. A total of 8 patients were noted to have inter-sphincteric recurrence and 8 patients had trans-sphincteric recurrence. Smoking at the time of surgery was significantly associated with LIFT failure (HR 3.18, 95% CI 1.18-8.61, p = 0.02). Other factors, such as age, sex, race, disease duration and location, type of fistula history of proctitis, preoperatively use of biologics or a seton, and previous repair attempts, did not appear to influence LIFT healing. Although not statistically significant, there was a trend toward increase in failure among patients with active proctitis at the time of surgery (HR 1.97, 95% CI 0.71-5.42, p = 0.19). CONCLUSION Our increasing experience with LIFT for anal fistula in CD demonstrates a higher rate of healing (65%) than previously reported (48%). Smoking appears to negatively influence healing of LIFT in CD.
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Affiliation(s)
- T Wood
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA
| | - A Truong
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA
| | - A Mujukian
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA
| | - K Zaghiyan
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA
| | - P Fleshner
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA.
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Abramowitz L, Brochard C, Pigot F, Roumeguere P, Pillant H, Vinson Bonnet B, Faucheron JL, Senéjoux A, Bonnaud G, Meurette G, Fayette JM, Train C, Staumont G, Siproudhis L, Bouchard D. Surgical closure, mainly with glue injection and anti-tumour necrosis factor α, in fistulizing perianal Crohn's disease: A multicentre randomized controlled trial. Colorectal Dis 2022; 24:210-219. [PMID: 34623746 DOI: 10.1111/codi.15947] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 06/15/2021] [Accepted: 06/16/2021] [Indexed: 12/14/2022]
Abstract
AIM In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab. METHODS This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end-point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula-related abnormalities. RESULTS Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000). CONCLUSIONS Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.
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Affiliation(s)
- Laurent Abramowitz
- Service d'Hépato-gastroentérologie et Proctologie, Hôpital Bichat-Claude Bernard, Paris, France.,Ramsay Général de Santé, Clinique Blomet, Paris, France
| | - Charlène Brochard
- Service des Maladies de l'Appareil Digestif, CHU Pontchaillou, Université de Rennes 1, Rennes, France.,CIC 1414, INPHY, Université de Rennes 1, Rennes, France
| | - François Pigot
- Service de Proctologie, Hôpital Bagatelle, Maison de Santé Protestante Bagatelle, Talence, France
| | | | - Hélène Pillant
- Service de Proctologie, Groupe Hospitalier Paris Saint Joseph, Institut Léopold-Bellan, Paris, France
| | - Béatrice Vinson Bonnet
- Service de Chirurgie Viscérale et Digestive, CHI, Poissy-St-Germain-en-Laye, Paris, France
| | - Jean Luc Faucheron
- Unité de Chirurgie Colo-rectale, Service de Chirurgie Digestive et de l'Urgence, Hôpital Michallon, CHUGA, Grenoble, France
| | | | | | - Guillaume Meurette
- Clinique de Chirurgie Digestive et Endocrinienne (CCDE), Institut des Maladies de l'Appareil Digestif (IMAD), University Hospital of Nantes, Nantes, France
| | | | | | | | - Laurent Siproudhis
- Service des Maladies de l'Appareil Digestif, CHU Pontchaillou, Université de Rennes 1, Rennes, France.,CIC 1414, INPHY, Université de Rennes 1, Rennes, France
| | - Dominique Bouchard
- Service de Proctologie, Hôpital Bagatelle, Maison de Santé Protestante Bagatelle, Talence, France
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Geldof J, Iqbal N, Warusavitarne J, Hart A. The Essential Role of a Multidisciplinary Approach in Inflammatory Bowel Diseases: Combined Medical-Surgical Treatment in Complex Perianal Fistulas in CD. Clin Colon Rectal Surg 2022; 35:21-31. [PMID: 35069027 PMCID: PMC8763455 DOI: 10.1055/s-0041-1740035] [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: 01/19/2023]
Abstract
Perianal fistulizing Crohn's disease (PFCD) represents a challenging and complex disease phenotype. Patients typically suffer a more severe disease course than those without perianal complications and are often managing debilitating symptoms. Etiology is understood to be multifactorial, with genetic predisposition, microbiological insult, aberrant immunity, and mechanical factors all implicated. As a result, multimodal treatment strategies must be employed to achieve disease control and fistula closure. This requires the complimentary involvement of medical and surgical disciplines in order to ensure thorough assessment and treatment tailored to the individual scenario and patient goals. The aim of this article is to describe an overview of the various treatment strategies available for PFCD, focusing on how a synergistic approach is required to ensure maximal chances of success.
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Affiliation(s)
- Jeroen Geldof
- IBD Unit, St. Mark's Hospital, Harrow, United Kingdom,Gastroenterology Department, University Hospital Ghent, Ghent, Belgium,Address for correspondence Jeroen Geldof, MD IBD Unit, St. Mark's HospitalWatford Road, Harrow HA1 3UJUnited Kingdom
| | - Nusrat Iqbal
- Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom
| | | | - Ailsa Hart
- IBD Unit, St. Mark's Hospital, Harrow, United Kingdom,Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom
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Yzet C, Brazier F, Sabbagh C, Fumery M. Managing complex perianal disease after anti-TNF failure: Where to go next? CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2022; 3:100081. [PMID: 35106477 PMCID: PMC8784625 DOI: 10.1016/j.crphar.2022.100081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 01/10/2022] [Accepted: 01/10/2022] [Indexed: 12/05/2022] Open
Abstract
Crohn's disease is a chronic inflammatory bowel disease that affects various intestinal segments and can involve the perianal region. Although anti-tumor necrosis factor (TNF) agents have revolutionized the management of Crohn's disease and improved the prognosis for patients with perianal Crohn's disease (pCD), their long-term effectiveness is limited: over 60% of patients relapse after one year of maintenance therapy. In recent years, significant advances have been made in the treatment of complex perianal fistulas after anti-TNF failure. Concomitant treatment with antibiotics and immunosuppressants improves the effectiveness of anti-TNF agents. Therapeutic drug monitoring and dose adjustment of anti-TNF therapy (targeting a higher trough level) might also improve treatment response. Novel therapeutic strategies might provide new opportunities for pCD management; for example, ustekinumab might be effective after anti-TNF treatment failure, although more studies are needed. As suggested in recent international guidelines, mesenchymal stem cell injection might be an effective, safe treatment for complex pCD.
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Affiliation(s)
- Clare Yzet
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Franck Brazier
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Charles Sabbagh
- Digestive Surgery Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
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Zhu P, Sun JF, Gu YF, Chen HJ, Xu MM, Li YR, Yang BL. Combined therapy with early initiation of infliximab following drainage of perianal fistulising Crohn's disease: a retrospective cohort study. BMC Gastroenterol 2022; 22:15. [PMID: 35012467 PMCID: PMC8751033 DOI: 10.1186/s12876-021-02078-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 12/21/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Recent studies have confirmed that combined surgery and anti-TNF therapy could improve outcomes in patients with perianal fistulising Crohn's disease (PFCD). However, the optimal timing for infliximab infusion after surgical intervention is uncertain. We aimed to determine the long-term efficacy of early initiation of infliximab following surgery among PFCD patients. METHODS We performed a retrospective cohort study of PFCD patients who received combined infliximab and surgical treatment between 2010 and 2018 at a tertiary referral hospital. Patients were grouped according to the time interval between surgery and infliximab infusion, with < 6 weeks into early infliximab induction group and > 6 weeks into delayed infliximab induction group. The primary outcome was to compare surgical re-intervention between early and delayed infliximab induction groups. The secondary outcomes were fistula healing and predictors associated with these outcomes of early infliximab induction approach. RESULTS One hundred and seventeen patients were included (73 in early infliximab induction, 44 in delayed infliximab induction). The median interval between surgery and infliximab initiation was 9.0 (IQR 5.5-17.0) days in early infliximab induction group and 188.0 (IQR 102.25-455.75) days in delayed infliximab induction group. After followed-up for a median of 36 months, 61.6% of patients in early infliximab induction group and 65.9% in delayed infliximab induction group attained fistula healing (p = 0.643). The cumulative re-intervention rate was 23%, 32%, 34% in early infliximab induction group and 16%, 25%, 25% in delayed infliximab induction group, at 1, 2, and 3 years respectively (p = 0.235). Presence of abscess at baseline (HR = 5.283; 95% CI, 1.61-17.335; p = 0.006) and infliximab maintenance therapy > 3 infusions (HR = 3.691; 95% CI, 1.233-11.051; p = 0.02) were associated with re-intervention in early infliximab induction group. Presence of abscess at baseline also negatively influenced fistula healing (HR = 3.429, 95% CI, 1.216-9.668; p = 0.02). CONCLUSION Although no clear benefit was shown compared with delayed infliximab induction group, early initiation of infliximab after surgery could achieve promising results for PFCD patients. Before infliximab infusion, durable drainage is required for patients with concomitant abscess or prolonged infliximab maintenance therapy.
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Affiliation(s)
- Ping Zhu
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - Jin-Fang Sun
- Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China
| | - Yun-Fei Gu
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - Hong-Jin Chen
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - Min-Min Xu
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - You-Ran Li
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - Bo-Lin Yang
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China.
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An Affordable Approach of Mesenchymal Stem Cell Therapy in Treating Perianal Fistula Treatment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1401:73-95. [DOI: 10.1007/5584_2022_716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Fathallah N, Cristea C, Beaussier H, Khirani S, de Parades V. Infliximab for Anoperineal Lesions in Crohn's Disease: Remission Appears to be Based on Rapid Combination Therapy at High Doses. JOURNAL OF COLOPROCTOLOGY 2021. [DOI: 10.1055/s-0041-1739549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Abstract
Study Aim The aim of the present study was to compare in real life the characteristics of treatment with infliximab according to the presence or absence of anoperineal involvement in Crohn's disease.
Methods We performed a single-center, prospective, non-interventional study, on patients with Crohn's disease in remission who had been treated with infliximab for at least 1 year. Patients with poor treatment compliance, on antibiotics, or those with a stoma were excluded.
Results We included 52 patients in this study: 34 with anoperineal lesions with or without luminal lesions, and 18 with luminal lesions only. Patients with anoperineal lesions were more likely to have undergone surgery (70.6% versus 38.9%, p = 0.027), had a shorter median time to infliximab treatment initiation (0.5 versus 5.5 years, p = 0.005), a higher mean dose of infliximab (6.6 versus 5.1 mg/kg, p = 0.015), and were more likely to receive combination treatments including infliximab (52.9% versus 11.1%, p = 0.008) than patients with luminal involvement only.
Conclusions In our study, infliximab treatment was initiated more quickly, at higher doses, and more in combination therapy for anoperineal Crohn's disease than for luminal damage alone. Additional studies are required to confirm this finding and to assess the tolerance of this treatment throughout patient management.
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Affiliation(s)
- Nadia Fathallah
- Groupe Hospitalier Paris Saint-Joseph, MedicoSurgical Proctology Department, Paris, France
| | - Cosmin Cristea
- Groupe Hospitalier Paris Saint-Joseph, MedicoSurgical Proctology Department, Paris, France
| | - Hélène Beaussier
- Groupe Hospitalier Paris Saint-Joseph, Clinical Research Center, Paris, France
| | - Sonia Khirani
- Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Clinical Investigation Center, Paris, France
| | - Vincent de Parades
- Groupe Hospitalier Paris Saint-Joseph, MedicoSurgical Proctology Department, Paris, France
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Łodyga M, Eder P, Gawron-Kiszka M, Dobrowolska A, Gonciarz M, Hartleb M, Kłopocka M, Małecka-Wojciesko E, Radwan P, Reguła J, Zagórowicz E, Rydzewska G. Guidelines for the management of patients with Crohn's disease. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. PRZEGLAD GASTROENTEROLOGICZNY 2021; 16:257-296. [PMID: 34976235 PMCID: PMC8690943 DOI: 10.5114/pg.2021.110914] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 10/25/2021] [Indexed: 12/13/2022]
Abstract
This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2012. It contains 46 recommendations for the diagnosis and treatment, both pharmacological and surgical, of Crohn's disease in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality and strength of the available recommendations. The degree of expert support for the proposed statement, assessment of the quality of evidence and the strength of the recommendation was assessed on a 6-point Likert scale. Voting results, quality and strength ratings with comments are included with each statement.
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Affiliation(s)
- Michał Łodyga
- Department of Gastroenterology with the Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland
| | - Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Heliodor Święcicki University Hospital, Poznan, Poland
| | - Magdalena Gawron-Kiszka
- Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Heliodor Święcicki University Hospital, Poznan, Poland
| | - Maciej Gonciarz
- Department of Gastroenterology and Internal Medicine, Military Institute of Medicine, Warsaw, Poland
| | - Marek Hartleb
- Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
| | - Maria Kłopocka
- Department of Gastroenterology and Nutritional Disorders, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | | | - Piotr Radwan
- Department of Gastroenterology, Medical University of Lublin, Lublin, Poland
| | - Jarosław Reguła
- Department of Gastroenterology, Hepatology and Clinical Oncology, Center of Postgraduate Medical Education, Warsaw, Poland
- Department of Oncological Gastroenterology, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Edyta Zagórowicz
- Department of Gastroenterology, Hepatology and Clinical Oncology, Center of Postgraduate Medical Education, Warsaw, Poland
- Department of Oncological Gastroenterology, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Grażyna Rydzewska
- Department of Gastroenterology with the Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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Alyami A, Hoad CL, Tench C, Bannur U, Clarke C, Latief K, Argyriou K, Lobo A, Lung P, Baldwin-Cleland R, Sahnan K, Hart A, Limdi JK, Mclaughlin J, Atkinson D, Parker GJM, O’Connor JPB, Little RA, Gowland PA, Moran GW. Quantitative Magnetic Resonance Imaging in Perianal Crohn's Disease at 1.5 and 3.0 T: A Feasibility Study. Diagnostics (Basel) 2021; 11:2135. [PMID: 34829482 PMCID: PMC8624877 DOI: 10.3390/diagnostics11112135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/08/2021] [Accepted: 11/12/2021] [Indexed: 01/06/2023] Open
Abstract
Perianal Crohn's Disease (pCD) is a common manifestation of Crohn's Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn's Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.
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Affiliation(s)
- Ali Alyami
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia;
- Translational Medical Sciences Academic Unit, School of Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2UH, UK;
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
| | - Caroline L. Hoad
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2QX, UK
| | - Christopher Tench
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
- Division of Clinical Neurosciences, Clinical Neurology, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK
| | - Uday Bannur
- Department of Radiology, Queens Medical Centre Campus, Nottingham University Hospitals, Nottingham NG7 2UH, UK; (U.B.); (C.C.); (K.L.)
| | - Christopher Clarke
- Department of Radiology, Queens Medical Centre Campus, Nottingham University Hospitals, Nottingham NG7 2UH, UK; (U.B.); (C.C.); (K.L.)
| | - Khalid Latief
- Department of Radiology, Queens Medical Centre Campus, Nottingham University Hospitals, Nottingham NG7 2UH, UK; (U.B.); (C.C.); (K.L.)
| | - Konstantinos Argyriou
- Translational Medical Sciences Academic Unit, School of Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2UH, UK;
| | - Alan Lobo
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, UK;
| | - Philip Lung
- Department of Radiology, St Mark’s Hospital and Academic Institute, London North West Healthcare NHS Trust, London HA1 3UJ, UK; (P.L.); (R.B.-C.)
| | - Rachel Baldwin-Cleland
- Department of Radiology, St Mark’s Hospital and Academic Institute, London North West Healthcare NHS Trust, London HA1 3UJ, UK; (P.L.); (R.B.-C.)
| | - Kapil Sahnan
- Fistula Research Unit, St Mark’s Hospital and Academic Institute, London North West Healthcare NHS Trust, London HA1 3UJ, UK; (K.S.); (A.H.)
| | - Ailsa Hart
- Fistula Research Unit, St Mark’s Hospital and Academic Institute, London North West Healthcare NHS Trust, London HA1 3UJ, UK; (K.S.); (A.H.)
| | - Jimmy K. Limdi
- Department of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Greater Manchester, Crumpsall M8 5RB, UK;
| | - John Mclaughlin
- Department of Gastroenterology, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre, Salford M6 8HD, UK;
| | - David Atkinson
- Centre for Medical Imaging, University College London, London W1W 7TS, UK;
| | - Geoffrey J. M. Parker
- Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London WC1V 6LJ, UK;
- Bioxydyn Limited, Manchester M15 6SZ, UK
| | - James P. B. O’Connor
- Quantitative Biomedical Imaging Laboratory, Division of Cancer Science, University of Manchester, Manchester M13 9PL, UK (R.A.L.)
| | - Ross A. Little
- Quantitative Biomedical Imaging Laboratory, Division of Cancer Science, University of Manchester, Manchester M13 9PL, UK (R.A.L.)
| | - Penny A. Gowland
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2QX, UK
| | - Gordon W. Moran
- Translational Medical Sciences Academic Unit, School of Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2UH, UK;
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
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Albader F, Golovics PA, Gonczi L, Bessissow T, Afif W, Lakatos PL. Therapeutic drug monitoring in inflammatory bowel disease: The dawn of reactive monitoring. World J Gastroenterol 2021; 27:6231-6247. [PMID: 34712029 PMCID: PMC8515794 DOI: 10.3748/wjg.v27.i37.6231] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/08/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition that significantly affects the quality of life of its patients. Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution, there remains a proportion of patients that do not respond or lose response to treatment. Therapeutic drug monitoring (TDM) involves measuring levels of serum drug concentrations and anti-drug antibodies. TDM of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory diseases. This was then introduced in IBD to rationalize primary non-response or secondary loss of response, given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment failure. The aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations, in everyday practice. A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management, through an electronic search using PubMed and ScienceDirect. TDM has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in treatment. Despite a trend towards an association between clinical outcomes and drug concentrations, proactive TDM based strategies have not been shown to achieve clear benefit in long-term outcomes. In the clinical setting, TDM has proven to be useful in managing IBD patients, and its use in the reactive setting, as an additional tool to help manage patients with treatment failure, is being promoted as newer guidelines and consensus groups implement TDM as part of the management plan.
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Affiliation(s)
- Farah Albader
- Department of Internal Medicine, McGill University, Montreal H3G1A4, Quebec, Canada
| | - Petra Anna Golovics
- Division of Gastroenterology, Hungarian Defence Forces, Medical Centre, Budapest H-1062, Hungary
- Division of Gastroenterology, McGill University, Montreal H3G 1A4, Quebec, Canada
| | - Lorant Gonczi
- First Department of Medicine, Semmelweis University, Budapest H-1083, Hungary
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Centre, Montreal H3G 1A4, Quebec, Canada
| | - Waqqas Afif
- Division of Gastroenterology, McGill University, Montreal H3G 1A4, Quebec, Canada
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, McGill University, Montreal H3G 1A4, Quebec, Canada
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van Rijn KL, Meima-van Praag EM, Bossuyt PM, D’Haens GR, Gecse KB, Horsthuis K, Snijder HJ, Tielbeek JAW, Buskens CJ, Stoker J. Fibrosis and MAGNIFI-CD Activity Index at Magnetic Resonance Imaging to Predict Treatment Outcome in Perianal Fistulizing Crohn's Disease Patients. J Crohns Colitis 2021; 16:708-716. [PMID: 34644395 PMCID: PMC9228904 DOI: 10.1093/ecco-jcc/jjab168] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Characteristic magnetic resonance imaging [MRI] features associated with long-term perianal fistula closure are still being discussed. This study evaluated the predictive value of degree of fibrosis and disease activity (MAGNIFI-CD index) at MRI for long-term clinical closure of Crohn's perianal fistulas. METHODS Crohn's disease [CD] patients treated with surgical closure following anti-tumour necrosis factor [anti-TNF] induction or anti-TNF alone for high perianal fistulas as part of a patient preference randomized controlled trial [PISA-II] between 2013 and 2020 with a post-treatment MRI and long-term clinical follow-up data were retrospectively included. Two radiologists scored the degree of fibrosis and MAGNIFI-CD index at pre- and post-treatment MRI. The accuracy of post-treatment MRI findings in predicting long-term clinical closure [12 months after the MRI] was evaluated using receiver operating characteristics [ROC] analysis. RESULTS Fifty patients were included: 31 female, median age 33 years (interquartile range [IQR] 26-45). Fourteen patients showed a 100% fibrotic fistula at post-treatment MRI, all of which had long-term clinical closure. Median MAGNIFI-CD index at post-treatment MRI was 0 [IQR 0-5] in 25 patients with long-term clinical closure and 16 [IQR 10-20] in 25 patients without. ROC analysis showed an area under the curve of 0.90 (95% confidence interval [CI] 0.82-0.99) for degree of fibrosis and 0.95 [95% CI 0.89-1.00] for the MAGNIFI-CD index, with a Youden cut-off point of 6 [91% specificity, 87% sensitivity]. CONCLUSIONS Degree of fibrosis and MAGNIFI-CD index at post-treatment MRI are accurate in predicting long-term clinical closure and seem valuable in follow-up of perianal CD. A completely fibrotic tract at MRI is a robust indicator for long-term fistula closure. EUDRACT 2013-002932-25 and 2018-002064-15.
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Affiliation(s)
- Kyra L van Rijn
- Corresponding author: Kyra L. van Rijn, MD, Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Tel: +31 (0) 20 7320783;
| | - Elise M Meima-van Praag
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Patrick M Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Geert R D’Haens
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Krisztina B Gecse
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Karin Horsthuis
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, De Boelelaan 1117, Amsterdam, The Netherlands
| | - Harmanna J Snijder
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Jeroen A W Tielbeek
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands,Department of Radiology, Spaarne Gasthuis, Haarlem, The Netherlands
| | - Christianne J Buskens
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
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Buscail E, Le Cosquer G, Gross F, Lebrin M, Bugarel L, Deraison C, Vergnolle N, Bournet B, Gilletta C, Buscail L. Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn's Disease: Rationale, Clinical Results and Perspectives. Int J Mol Sci 2021; 22:ijms22189967. [PMID: 34576129 PMCID: PMC8470328 DOI: 10.3390/ijms22189967] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/07/2021] [Accepted: 09/12/2021] [Indexed: 12/16/2022] Open
Abstract
Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.
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Affiliation(s)
- Etienne Buscail
- Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France;
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Guillaume Le Cosquer
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Fabian Gross
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Marine Lebrin
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Laetitia Bugarel
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Céline Deraison
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Nathalie Vergnolle
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Barbara Bournet
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Cyrielle Gilletta
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Louis Buscail
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
- Correspondence: ; Tel.: +33-561323055
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Deng F, Xia P, Wu Z, Zhou H, Wang X. Perianal and Luminal Relapse Following Perianal Surgical Intervention in Crohn's Disease. Int J Gen Med 2021; 14:3387-3396. [PMID: 34285563 PMCID: PMC8286149 DOI: 10.2147/ijgm.s315505] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/07/2021] [Indexed: 12/02/2022] Open
Abstract
Background and Aims Fistula relapse occurs in 20–30% of patients with perianal Crohn’s disease (PCD) despite optimal medico-surgical management. We aimed in this study to assess the rate of perianal and luminal relapse after surgically induced remission and to determine factors associated with fistula relapse. Methods Consecutive perianal CD patients who achieved clinical remission after surgery for fistulising PCD from January 2013 to January 2019 were included. The cumulative probabilities of relapse-free survival were estimated using the Kaplan–Meier method. Results A total of 130 patients were included. Sixty-six of 130 patients received infliximab (IFX) therapy after perianal surgery. After a median follow-up of 62 months (interquartile range [IQR]: 28–117 months), perianal relapse occurred in 30 of 64 (46.9%) nonbiological medication-treated cases and in 14 of 66 (21.1%) cases in the IFX therapy group. The cumulative probabilities of perianal relapse-free survival in patients with nonbiological treatment were 77.1% at 1 year, 54.6% at 3 years, and 30% at 5 years. The rates of survival without perianal fistula relapse in the IFX-treated group were 91.6%, 69.2%, and 59.3% at 1, 3 and 5 years, respectively. In patients treated with IFX after perianal surgery, discontinuation of IFX therapy (odds ratio [OR]=2.43, p=0.036), a penetrating CD phenotype (OR=4.324, p=0.019), and a complex perianal fistula (OR=3.392, p=0.026) were independently associated with perianal relapse in multivariate analysis. Conclusion Infliximab therapy reduced the risk of perianal relapse after surgical remission in PCD patients compared with nonbiological treatment. However, approximately 40% of patients using infliximab experienced perianal relapse at 5 years, and patients who discontinued use of IFX or experienced a penetrating phenotype or a complex perianal fistula were associated with increased relapse rate.
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Affiliation(s)
- Feihong Deng
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
| | - Pianpian Xia
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
| | - Zengrong Wu
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
| | - Hejun Zhou
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
| | - Xuehong Wang
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
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Park MY, Yoon YS, Lee JL, Park SH, Ye BD, Yang SK, Yu CS. Comparative perianal fistula closure rates following autologous adipose tissue-derived stem cell transplantation or treatment with anti-tumor necrosis factor agents after seton placement in patients with Crohn's disease: a retrospective observational study. Stem Cell Res Ther 2021; 12:401. [PMID: 34256838 PMCID: PMC8278611 DOI: 10.1186/s13287-021-02484-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/23/2021] [Indexed: 12/15/2022] Open
Abstract
Background Perianal fistula is one of the most common complications in Crohn’s disease, and various medical and surgical treatments are being tried. The aim of this study was to compare the perianal fistula closure rates following treatment with anti-tumor necrosis factor (TNF) agents or autologous adipose tissue-derived stem cell (auto-ASC) transplantation with Crohn’s disease (CD). Methods CD patients who underwent seton placement for perianal fistula from January 2015 to December 2019 at a tertiary referral center were retrospectively reviewed. Patients were divided into two groups, one that received sequential treatments with anti-TNF agents (anti-TNF group) and the other that underwent auto-ASC transplantation (stem cell group). Clinical variables and fistula closure rates were compared in the two groups. Results Of the 69 patients analyzed, 39 were treated with anti-TNF agents and 30 underwent auto-ASC transplantation. Compared with the stem cell group, patients in the anti-TNF group were older (p=0.028), were more frequently male (p=0.019), had fistulas with more penetrating behavior (p=0.002), had undergone surgery more frequently (p=0.010), and had a shorter interval from seton placement to intended treatment (p<0.001). During a median follow-up of 46 months (range, 30–52.5 months), fistula closure rates were significantly faster (83.3% vs. 23.1%, p<0.001), and the mean interval from seton placement to fistula closure significantly shorter (14 vs. 37 months, p<0.001) in the stem cell than in the anti-TNF group. Three patients experienced fistula recurrence, all in the stem cell group. Conclusions Medical treatment using anti-TNF agents and auto-ASC transplantation are feasible treatment options after seton placement for Crohn’s perianal fistula. However, the closure rate was significantly faster and the time to closure significantly shorter in patients who underwent auto-ASC transplantation than medical treatment. Trial registration This study was retrospectively registered and approved by the Institutional Review Board of Asan Medical Center, number 2020-1059.
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Affiliation(s)
- Min Young Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Yong Sik Yoon
- Department of Colon and Rectal Surgery, Asan Medical Center, University of College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Jong Lyul Lee
- Department of Colon and Rectal Surgery, Asan Medical Center, University of College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chang Sik Yu
- Department of Colon and Rectal Surgery, Asan Medical Center, University of College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
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Vasudevan A, Bruining DH, Loftus EV, Faubion W, Ehman EC, Raffals L. Approach to medical therapy in perianal Crohn's disease. World J Gastroenterol 2021; 27:3693-3704. [PMID: 34321838 PMCID: PMC8291021 DOI: 10.3748/wjg.v27.i25.3693] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/13/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Perianal Crohn's disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn's disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn's disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn's disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn's disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.
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Affiliation(s)
- Abhinav Vasudevan
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Edward V Loftus Jr
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - William Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Eric C Ehman
- Department of Radiology, Mayo Clinic, Rochester, MN 55905, United States
| | - Laura Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
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Kim PH, Kim SH, Cho YA, Yoon HM, Lee JS, Jung AY, Oh SH, Kim DY, Namgoong JM, Kim KM. Ability of Pelvic Magnetic Resonance Imaging to Predict Clinical Course of Perianal Fistula in Paediatric Crohn's Disease Patients. J Crohns Colitis 2021; 15:1152-1160. [PMID: 33411884 DOI: 10.1093/ecco-jcc/jjab004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Evidence is limited regarding clinical course and magnetic resonance imaging [MRI] features of perianal fistula [PAF] in Korean children with Crohn's disease [CD]. We investigated MRI features of PAF and associations with long-term outcomes. METHODS We retrospectively analysed 243 patients with pelvic MRI for diagnosis of CD. Incidence of clinically evident PAF at diagnosis was determined, as were the proportions of patients with clinical failure [failure to achieve fistula healing within 1 year] and recurrence [new/recurrent PAF after fistula healing within 1 year]. Associations between outcomes and MRI features, specified in modified Van Assche index and MAGNIFI-CD, were evaluated. Associations between later development of clinically evident PAF and subclinical PAF detected on MRI at diagnosis were evaluated. RESULTS Among 243 included patients, 108 [44.4%] and 76 [31.3%] had clinically evident and subclinical PAF at diagnosis, respectively; 66.4% of the patients with clinically evident PAF achieved fistula healing within 1 year, and 32.7% of those patients developed recurrence. Fistula length and dominant features of the tracts were associated with clinical failure, and fistula length was associated with recurrence. Clinically evident PAF developed in 17.0% of the patients without clinically evident PAF at diagnosis. We did not find statistically significant association between subclinical PAF and later development of clinically evident PAF [adjusted hazard ratio, 2.438; p = 0.15]. CONCLUSIONS A considerable proportion of Korean paediatric CD patients had clinically evident and subclinical PAF. Fistula length and dominant feature of the tract on MRI are useful predictors of outcomes.
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Affiliation(s)
- Pyeong Hwa Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seo Hee Kim
- Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Ah Cho
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hee Mang Yoon
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin Seong Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ah Young Jung
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seak Hee Oh
- Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dae Yeon Kim
- Department of Pediatric Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jung-Man Namgoong
- Department of Pediatric Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kyung Mo Kim
- Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Abstract
PURPOSE OF REVIEW Multiple new medications with novel mechanisms of action are now available to treat Crohn's disease (CD). However, they have varying effectiveness in the management of perianal CD. Identifying the most appropriate therapy and optimizing it is essential to maximize effectiveness of therapy. Additionally, the management of perianal CD requires imaging of the perianal area to identify the fistula anatomy and local complications such as abscesses that require surgical drainage. Initial surgical assessment is key to drain abscesses and allow fistula healing with medical therapy. RECENT FINDINGS Although anti-tumor necrosis factor (TNFs) remain the most effective medications to treat perianal CD, real-world data suggests that ustekinumab may be a 2nd-line option in patients nonresponsive to an anti-TNF or having contraindications. Mesenchymal stem cells are an emerging therapeutic approach that is currently in Phase 3 trials in the United States and poised to play a major role in the treatment algorithm. SUMMARY The management of perianal CD requires a multidisciplinary approach with a combination of initial imaging and surgical assessment to adequately control local sepsis, optimization of biological therapy with adjunct antibiotics or immunomodulators, and close clinical follow-up with imaging to evaluate response to therapy and guide further surgical management options.
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Nam K, Jung WB, Lee SB, Soh JS, Yang SS, Jung SW. Predictors of reoperation for perianal fistula in Crohn's disease. J Dig Dis 2021; 22:334-341. [PMID: 33949127 DOI: 10.1111/1751-2980.12996] [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: 09/28/2020] [Revised: 04/29/2021] [Accepted: 05/02/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Treating perianal fistula in cases of Crohn's disease (CD) remains challenging and the postoperative recurrence rate of perianal fistula is 22%-28%. This study aimed to identify the predictive risk factors for reoperation in Korean CD patients with perianal fistula. METHODS Medical records of the patients with clinically and pathologically confirmed CD who underwent surgical treatment for perianal fistulas at four referral centers in Korea between March 2010 and February 2020 were retrospectively reviewed. The rate of reoperation due to perianal fistula recurrence, which was defined as any subsequent surgery for perianal fistula or abscess, and the potential risk factors for reoperation were analyzed. RESULTS Fifty-one patients at a mean age of 22 years were included in the study. During a median follow-up period of 26 months (range 2-89 mo), 21 (41.2%) patients underwent reoperation because of recurrent perianal fistula or abscess. The median interval from the first surgery to reoperation was 13 months. A multivariate Cox regression analysis revealed that drug escalation (from 5-aminosalicylic acid [5-ASA] to thiopurine or from 5-ASA or thiopurine to anti-tumor necrosis factor agents) after the first surgery was associated with a reduced likelihood of reoperation (hazard ratio 0.316, 95% confidence interval 0.117-0.858, P = 0.024). CONCLUSIONS The postoperative recurrence rate was relatively high (41.2%) after the first surgery for perianal fistula in Korean patients with CD. Drug escalation therapy after the first surgery may help reduce the need for reoperation for perianal fistula.
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Affiliation(s)
- Kwangwoo Nam
- Department of Gastroenterology, Dankook University Hospital, Dankook University College of Medicine, Cheonan, South Korea
| | - Won Beom Jung
- Department of Surgery, Haeundae Paik Hospital, College of Medicine, University of Inje, Busan, South Korea
| | - Seung Bum Lee
- Department of Gastroenterology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Jae Seung Soh
- Department of Gastroenterology, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang, South Korea
| | - Song Soo Yang
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Seok Won Jung
- Department of Gastroenterology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
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Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases. J Clin Med 2021; 10:jcm10040853. [PMID: 33669579 PMCID: PMC7922976 DOI: 10.3390/jcm10040853] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 02/10/2021] [Accepted: 02/11/2021] [Indexed: 12/22/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.
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Wilson A, Choi B, Sey M, Ponich T, Beaton M, Kim RB. High infliximab trough concentrations are associated with sustained histologic remission in inflammatory bowel disease: a prospective cohort study. BMC Gastroenterol 2021; 21:77. [PMID: 33602145 PMCID: PMC7890824 DOI: 10.1186/s12876-021-01650-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 02/08/2021] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The threshold concentration of infliximab during maintenance therapy has not been well-defined in relation to histologic remission. The aim of the study is to dentify the maintenance-phase infliximab concentration associated with histologic remission in inflammatory bowel disease patients (IBD). METHODS A prospective cohort study was carried out in 104 IBD patients seen at a tertiary care centre in London, Canada. Infliximab trough concentrations were collected during the maintenance phase of treatment and compared between participants with and without evidence of histologic remission. Participants were additionally evaluated for sustained histologic remission, and relapse to active disease. RESULTS Participants in histologic remission attained higher mean concentrations of infliximab during the maintenance phase (10.34 ± 0.69 μg/ml) compared to those with persistent disease activity (6.23 ± 0.67 μg/ml, p-value < 0.0001). Additionally, during the maintenance phase, sustained histologic remission was also associated with a higher mean concentration of infliximab (10.81 ± 5.46 μg/ml) compared to those who relapsed to active disease (5.68 ± 3.70, p < 0.001). Overall, participants with a mean infliximab trough concentration greater than 8ug/ml were more likely to have histologic remission (area under the receiver operating characteristic curve, AUROC = 0.72, 95%CI = 0.65-0.84, p < 0.0001) and sustained histologic remission (AUC = 0.77, 95%CI = 0.63-0.91, p = 0.002). CONCLUSION Maintenance-phase infliximab trough concentrations greater than 8 μg/ml, which is higher than the currently recommended target concentration, are highly associated with histologic remission and sustained histologic remission.
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Affiliation(s)
- Aze Wilson
- Divisions of Clinical Pharmacology, Department of Medicine, Western University, 339 A Wilson 339 Windermere Road A10-221a, London, ON, N6A 5A5, Canada.
- Divisions of Gastroenterology, Department of Medicine, Western University, 339 Windermere Rd, London, ON, N6A 5A5, Canada.
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada.
| | - Bethany Choi
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada
| | - Michael Sey
- Divisions of Gastroenterology, Department of Medicine, Western University, 339 Windermere Rd, London, ON, N6A 5A5, Canada
| | - Terry Ponich
- Divisions of Gastroenterology, Department of Medicine, Western University, 339 Windermere Rd, London, ON, N6A 5A5, Canada
| | - Melanie Beaton
- Divisions of Gastroenterology, Department of Medicine, Western University, 339 Windermere Rd, London, ON, N6A 5A5, Canada
| | - Richard B Kim
- Divisions of Clinical Pharmacology, Department of Medicine, Western University, 339 A Wilson 339 Windermere Road A10-221a, London, ON, N6A 5A5, Canada
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada
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Herissay A, Siproudhis L, Le Balc'h E, Merlini L'Heritier A, Dewitte M, Wallenhorst T, Bouguen G, Brochard C. Combined strategies following surgical drainage for perianal fistulizing Crohn's disease: failure rates and prognostic factors. Colorectal Dis 2021; 23:159-168. [PMID: 32640112 DOI: 10.1111/codi.15241] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 06/21/2020] [Indexed: 12/13/2022]
Abstract
AIM The medico-surgical strategy for the treatment of perianal fistulizing Crohn's disease (CD) following surgical drainage remains challenging and debated. Our aims were to describe the failure rate of therapeutic interventions after drainage of the fistula tract and determine the factors associated with failure to optimize medico-surgical strategies. METHOD All consecutive patients with perianal fistulizing CD who underwent surgical drainage with at least a 12-week follow-up were included. Failure was defined as the occurrence of at least one of the following items: abscess recurrence, purulent discharge from the tract, visible external opening and further drainage procedure(s). RESULTS One hundred and sixty-nine patients were included. The median follow-up was 4.0 years. The cumulative failure rates were 20%, 30% and 36% at 1, 3 and 5 years, respectively. The cumulative failure rates in patients who had sphincter-sparing surgeries or seton removal were significantly higher than in those who had a fistulotomy. Anterior fistula [hazard ratio (HR) = 2.52 (1.13-5.61), P = 0.024], supralevator extension [HR = 20.78 (3.38-127.80), P = 0.001] and the absence or discontinuation of immunosuppressants after anal drainage [HR = 3.74 (1.11-12.5), P = 0.032] were significantly associated with failure in the multivariate analysis model. CONCLUSION Combined strategies for perianal fistulizing CD lead to a failure rate of 36% at 5 years. Where advisable, fistulotomy may be preferred because it has a lower rate of recurrence. The benefits of immunosuppressants require a dedicated prospective randomized trial.
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Affiliation(s)
- A Herissay
- CHU Rennes, Universitaire Rennes, Rennes, France
| | - L Siproudhis
- INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), CHU Rennes, Universitaire Rennes, Rennes, France
| | - E Le Balc'h
- CHU Rennes, Universitaire Rennes, Rennes, France
| | | | - M Dewitte
- CHU Rennes, Universitaire Rennes, Rennes, France
| | | | - G Bouguen
- INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), CHU Rennes, Universitaire Rennes, Rennes, France
| | - C Brochard
- INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), CHU Rennes, Universitaire Rennes, Rennes, France
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