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Anand E, Pelly T, Joshi S, Shakweh E, Hanna LN, Hart A, Tozer P, Lung P. Current practice and innovations in diagnosing perianal fistulizing Crohn's disease (pfCD): a narrative review. Tech Coloproctol 2025; 29:102. [PMID: 40232330 PMCID: PMC12000175 DOI: 10.1007/s10151-025-03122-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 02/23/2025] [Indexed: 04/16/2025]
Abstract
Perianal fistulizing Crohn's disease (pfCD) represents a severe manifestation of Crohn's disease (CD) that often leads to significant morbidity. Clinical examination alone of perianal fistulae is unlikely to be sufficient in the context of complex pfCD, as patients are likely to have complex disease and are more likely to experience complications, treatment failure, and recurrent disease. Furthermore, the relapsing-remitting nature of Crohn's disease and our limited understanding of the pathogenesis of this potentially destructive disease necessitate regular examination and radiological assessment, often in the form of magnetic resonance imaging (MRI). Recent advancements in diagnostic techniques have enhanced the accuracy and timeliness of pfCD diagnosis, facilitating better patient outcomes. A growing appreciation of isolated perianal Crohn's disease has prompted a recent attempt to develop consensus recommendations on diagnosing and treating this group of patients who would previously not have been offered CD medications. This narrative review aims to summarize current practice and the latest developments in the diagnosis of pfCD, highlighting: 1. Clinical examination and assessment tools 2. Current imaging practices 3. Innovations in imaging and biomarkers 4. The diagnosis of isolated perianal Crohn's disease.
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Affiliation(s)
- E Anand
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK.
- Imperial College London, London, UK.
| | - T Pelly
- Imperial College London, London, UK
| | - S Joshi
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - E Shakweh
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - L N Hanna
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - A Hart
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - P Tozer
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - P Lung
- Imperial College London, London, UK
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Khalil C, Mehra M, Yang Y, Choi SY, Ballesteros J, Krut Z, Bonthala N, Zaghiyan K, Gu P, Yeo YH, Spiegel BMR, Almario CV. Development and Validation of Crohn's Perianal Fistula Educational Videos and Website for Increasing Patient Knowledge and Engagement. J Clin Gastroenterol 2025:00004836-990000000-00440. [PMID: 40261667 DOI: 10.1097/mcg.0000000000002156] [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: 08/06/2024] [Accepted: 02/02/2025] [Indexed: 04/24/2025]
Abstract
INTRODUCTION There are few online resources that provide authoritative and comprehensive information on Crohn's perianal fistula (CPF). In this study, we aimed to use a human-centered design thinking approach to develop and validate 2 educational CPF videos and an accompanying website to support patients with CPF. METHODS We used a design thinking approach to understand the unmet educational needs of patients with CPF. We conducted 3 rounds of interviews with a diverse sample of patients with CPF and used the resulting insights to iteratively develop 2 unbranded educational videos optimized for social media and an accompanying website. To validate the 2 videos, we performed an online survey with CPF patients to assess the impact of the videos on patient activation as measured by the patient activation measure (PAM). RESULTS Our design thinking approach with 20 CPF patients allowed us to empathize with them, gain an in-depth understanding of their informational needs, and iteratively test and update the educational materials based on their input. Using their feedback, we created 2 videos ("What is a Crohn's perianal fistula?" and "How to treat Crohn's perianal fistula?") and a corresponding website called "Heal My Fistula." In qualitative testing, patients described both videos and the website as "accurate", "informative", "simple", "easy to understand", and in line with their expectations. In validation testing through a pre-post survey (N=357), both videos led to statistically significant improvements in PAM scores (P<0.001). CONCLUSION Through a human-centered design thinking approach, we developed and validated 2 informative videos and a website (healmyfistula.org) for addressing the educational needs of patients with CPF.
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Affiliation(s)
- Carine Khalil
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE)
| | - Muskaan Mehra
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE)
| | - Yixin Yang
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE)
| | - So Yung Choi
- Biostatistics Shared Resource, Cedars-Sinai Cancer
| | - Jan Ballesteros
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE)
| | - Zoe Krut
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE)
| | | | | | - Phillip Gu
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
| | - Yee Hui Yeo
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE)
- Department of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Brennan M R Spiegel
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE)
- Department of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Christopher V Almario
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE)
- Department of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA
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Beek KJ, Mulders LGM, van Rijn KL, Horsthuis K, Tielbeek JAW, Buskens CJ, D'Haens GR, Gecse KB, Stoker J. External validation of the MAGNIFI-CD index in patients with complex perianal fistulising Crohn's disease. Eur Radiol 2025; 35:1428-1439. [PMID: 39212672 PMCID: PMC11836172 DOI: 10.1007/s00330-024-11029-3] [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: 05/13/2024] [Revised: 06/14/2024] [Accepted: 07/23/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND There is an increasing need for objective treatment monitoring in perianal fistulising Crohn's disease (pfCD). Therefore, the magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD) index has been designed and internally validated on the ADMIRE-CD trial cohort. The aim of this study was to externally validate the MAGNIFI-CD index to monitor response to medical and surgical treatment regimens in pfCD. METHODS A retrospective longitudinal cohort was established of consecutive patients with complex pfCD treated with surgical and/or medical therapy and a baseline and follow-up MRI between January 2007 and May 2021. The MAGNIFI-CD index was scored by two independent, abdominal radiologists blinded for time points and clinical outcomes. Responsiveness, reliability, and test accuracy regarding clinically important improvement were assessed. Cut-offs for response and remission were selected classified on fistula drainage assessment and physician global assessment. RESULTS A total of 65 patients (51% female, median age 32 years) were included. A clinically relevant responsiveness of the MAGNIFI-CD was shown, with a significant decrease in clinical remitters and responders with a median MAGNIFI-CD of 18.0 [7.5-20.0] to 9.0 [0.8-16.0] (p < 0.001) and non-significant change in non-responders with a median MAGNIFI-CD of 20.0 [12.0-23.0] to 18.0 [13.0-21.0] (p = 0.22). There was an 'almost perfect' interobserver agreement (ICC = 0.87; 95% CI 0.80-0.92) for the MAGNIFI-CD index. An optimal cut-off value was defined as a decrease of 2 points for clinical response, and a MAGNIFI-CD ≤ 6 for remission at follow-up MRI. CONCLUSION The MAGNIFI-CD index is a responsive and reliable MRI scoring instrument for treatment monitoring in perianal fistulising Crohn's disease. CLINICAL RELEVANCE STATEMENT The MAGNIFI-CD index is a well-structured, responsive scoring instrument to assess fistula severity and activity that allows quantitative detection of changes in therapy response in patients with perianal fistulising Crohn's disease, thereby facilitating endpoints in clinical trials. KEY POINTS Well-defined cut-offs for response and remission are needed for objective treatment monitoring of perianal fistulising Crohn's disease (pfCD). Cut-off values for remission and for response at 6 months follow-up were defined. Interobserver agreement was good. The MAGNIFI-CD index is responsive and reliable for treatment monitoring and is suitable for use in clinical trials.
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Affiliation(s)
- Kim J Beek
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Lieven G M Mulders
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Kyra L van Rijn
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Karin Horsthuis
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location Vrije Universiteit, De Boelelaan 1117, Amsterdam, The Netherlands
| | - Jeroen A W Tielbeek
- Spaarne Gasthuis, Department of Radiology and Nuclear Medicine, Boerhaavelaan 22, Haarlem, The Netherlands
| | - Christianne J Buskens
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Geert R D'Haens
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Krisztina B Gecse
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
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De Gregorio M, Winata LS, Hartley I, Behrenbruch CC, Connor SJ, D‘Souza B, Basnayake C, Guerra GR, Johnston MJ, Kamm MA, Keck JO, Lust M, Niewiadomski O, Ong EJS, Schulberg JD, Srinivasan A, Sutherland T, Woods RJ, Wright EK, Connell WR, Thompson AJ, Ding NS. A new protocolized treatment strategy optimizing medical and surgical care leads to improved healing of Crohn's perianal fistulas. J Crohns Colitis 2025; 19:jjae199. [PMID: 39756400 PMCID: PMC11772862 DOI: 10.1093/ecco-jcc/jjae199] [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: 08/08/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND AND AIMS Crohn's perianal fistula healing rates remain low. We evaluated the efficacy of a protocolized multidisciplinary treatment strategy optimizing care in adults with Crohn's perianal fistulas. METHODS A new treatment strategy was established at a single tertiary center. The strategy comprised 3 dynamic stages of care directed toward achieving and maintaining fistula healing. Stage A, active disease, focused on early commencement and proactive escalation of biologic therapies and structured surgical reviews ensuring adequate fistula drainage and conditioning. Stage B, optimized disease with a seton in situ, focused on consideration for seton removal and appropriateness of definitive surgical closure and/or ablative techniques. Stage C, healed disease, focused on proactive care maintenance. Sixty patients were sequentially enrolled and prospectively followed for ≥12 months. Endpoints included clinical healing and radiologic remission in those with clinically active fistulas, and relapse in those with healed fistulas. RESULTS At baseline, 52% (n = 31) and 48% (n = 29) had clinically active and healed fistulas, respectively. For patients with clinically active fistulas, 71% achieved clinical healing after 22 months, with estimated healing rates of 39% and 84% at 1 and 2 years, respectively. Radiologic remission was achieved in 25%, significantly higher than baseline inclusion rates of 6%. For patients with healed fistulas, 7% experienced clinical relapse after 23 months, with no significant change in radiologic remission, 80% versus 86% at baseline. CONCLUSIONS A protocolized treatment strategy proactively optimizing care resulted in high rates of clinical healing and improved radiologic remission of Crohn's perianal fistulas. Controlled-matched studies are needed.
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Affiliation(s)
- Michael De Gregorio
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Leon S Winata
- Department of Medical Imaging, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Imogen Hartley
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Corina C Behrenbruch
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
- Department of Colorectal Surgery, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Susan J Connor
- Department of Gastroenterology, Liverpool Hospital Sydney, Liverpool, New South Wales, Australia
- Department of UNSW Medicine & Health, UNSW Sydney, South West Sydney Clinical Campuses, Sydney, New South Wales, Australia
| | - Basil D‘Souza
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
- Department of Colorectal Surgery, Northern Hospital, Epping, Victoria, Australia
| | - Chamara Basnayake
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Glen R Guerra
- Department of Colorectal Surgery, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
| | - Michael J Johnston
- Department of Colorectal Surgery, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - James O Keck
- Department of Colorectal Surgery, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Mark Lust
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Ola Niewiadomski
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Eugene J S Ong
- Department of Colorectal Surgery, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Julien D Schulberg
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Ashish Srinivasan
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
- Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia
- Department of Gastroenterology, Eastern Health, Box Hill, Victoria, Australia
| | - Tom Sutherland
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
- Department of Medical Imaging, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Rodney J Woods
- Department of Colorectal Surgery, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - William R Connell
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Alexander J Thompson
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Nik S Ding
- Department of Gastroenterology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
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Karki C, Hantsbarger G, Turkstra E, Fenu E, Genenz K, Gilaberte I, Panés J. Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in patients with complex perianal fistulas in Crohn's disease. BMC Gastroenterol 2024; 24:479. [PMID: 39736547 DOI: 10.1186/s12876-024-03513-3] [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: 02/14/2024] [Accepted: 11/12/2024] [Indexed: 01/01/2025] Open
Abstract
BACKGROUND Current therapies for complex Crohn's perianal fistulas (CPF) have a limited ability to achieve long-term healing. Darvadstrocel (DVS) is an expanded allogeneic adipose-derived mesenchymal stem cell therapy that has demonstrated efficacy in treating complex CPF in clinical trials. There are, however, limited long-term comparative data with standard of care (SoC). The aim of this study was to combine clinical trial data and real-world evidence using statistical methodologies to predict long-term effectiveness of DVS versus SoC in patients with CPF. METHODS Data were pooled from a clinical trial (ADMIRE-CD) and two retrospective chart review studies (INSPECT and PREFACE). Predictive statistical models extrapolated clinical outcomes beyond observed follow-up using parametric curves, which were implemented into a semi-Markov model to obtain the number of patients in remission. The setting was multinational and multicenter. ADMIRE-CD was conducted in 49 hospitals in 7 European countries and Israel. INSPECT used data from the ADMIRE study. PREFACE involved patients from Belgium, France, Germany, Italy, and Spain. The participants were patients with complex CPF treated with DVS or SoC. Times to remission and relapse (clinical, and clinical plus patient-centric remission) were analyzed. Additionally, the proportion of patients in clinical and patient-centric remission was examined. RESULTS In total, 513 patients were included in the analysis (ADMIRE-CD [N = 200] and PREFACE [N = 313]). Patients in ADMIRE-CD and PREFACE were similar in age (median [interquartile range, IQR], 36 [20.0] versus 36 [22.0] years, respectively) and gender (males, 54% and 52%, respectively). The median (IQR) duration of Crohn's disease was 9.4 [11.3] years for patients in ADMIRE-CD and 6.5 [12.9] years for patients in PREFACE. The estimated time to remission was shorter for patients treated with DVS versus SoC. The estimated time to relapse was longer for patients treated with DVS versus SoC. A higher estimated proportion of patients treated with DVS versus SoC had clinical and patient-centric remission at 24 months (48% and 35%, respectively) and 48 months (49% and 32%, respectively). CONCLUSION This novel approach enabled pooled data from a clinical trial and real-world settings to predict long-term effectiveness of DVS versus SoC in patients with complex CPF.
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Affiliation(s)
| | | | | | | | - Ken Genenz
- Takeda Pharmaceuticals, Zurich, Switzerland
| | | | - Julián Panés
- Formerly Gastroenterology Department, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital Clínic de Barcelona, Barcelona, Spain.
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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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Schroeder MK, Abushamma S, George AT, Ravella B, Hickman J, Elumalai A, Wise P, Zulfiqar M, Ludwig DR, Shetty A, Viswanath SE, Luo C, Sebastian S, Ballard DH, Deepak P. TOpCLASS Expert Consensus Classification of Perianal Fistulising Crohn's Disease: A Real-world Application in a Serial Fistula MRI Cohort. J Crohns Colitis 2024; 18:1430-1439. [PMID: 38642332 DOI: 10.1093/ecco-jcc/jjae056] [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: 01/07/2024] [Revised: 03/09/2024] [Accepted: 04/16/2024] [Indexed: 04/22/2024]
Abstract
BACKGROUND AND AIMS Perianal fistuliing Crohn's disease [PFCD] is an aggressive phenotype of Crohn's disease defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by the TOpCLASS consortium, which seeks to unify disease severity with patient-centred goals but has not yet been validated. We aimed to apply this to a real-world cohort and to identify factors that predict transition between classes over time. METHODS We identified all patients with PFCD and at least one baseline and one follow-up pelvic MRI [pMRI]. TOpCLASS classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs. RESULTS We identified 100 patients with PFCD, of whom 96 were assigned TOpCLASS Classes 1-2c at baseline. Most patients [78.1%] started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex [72.0%, 46.6%, 40.0%, p = 0.03] and prior perianal surgery [52.0% vs 44.6% vs 40.0%, p = 0.02] were more frequently observed in those with improved class compared to unchanged and worsened class. Baseline pMRI indices were not associated with changes in classification; however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modelling identified only male sex [-0.31, 95% CI -0.60 to -0.02] with improvement in class. CONCLUSION The TOpCLASS classification highlights the dynamic nature of PFCD over time. However, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower TOpCLASS classification.
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Affiliation(s)
- Matthew K Schroeder
- Division of Gastroenterology, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | - Suha Abushamma
- Division of Gastroenterology, Cleveland Clinic, Cleveland, OH, USA
| | - Alvin T George
- Division of Gastroenterology, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | | | - John Hickman
- Division of Gastroenterology, University of Virginia, Charlottesville, VA, USA
| | - Anusha Elumalai
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | - Paul Wise
- Section of Colon and Rectal Surgery, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | - Maria Zulfiqar
- Department of Radiology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Daniel R Ludwig
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | - Anup Shetty
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | - Satish E Viswanath
- Department of Biomedical Engineering, School of Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Chongliang Luo
- Division of Public Health Sciences, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | | | - David H Ballard
- Division of Gastroenterology, Cleveland Clinic, Cleveland, OH, USA
| | - Parakkal Deepak
- Division of Gastroenterology, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
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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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9
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Vuyyuru SK, Solitano V, Singh S, Hanzel J, Macdonald JK, Danese S, Peyrin Biroulet L, Ma C, Jairath V. Scoring Indices for Perianal Fistulising Crohn's Disease: A Systematic Review. J Crohns Colitis 2024; 18:836-850. [PMID: 38126903 DOI: 10.1093/ecco-jcc/jjad214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 11/20/2023] [Accepted: 12/18/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND AND AIMS In this systematic review we summarise existing scoring indices for assessing disease activity and quality of life in perianal fistulising Crohn's disease [PFCD], and highlight gaps in the literature. METHODS MEDLINE, EMBASE, and CENTRAL were searched from August 24, 2022, to identify studies evaluating clinical, radiological, or patient-reported outcome measures [PROMS] in PFCD. The primary objective was to identify all available scoring indices and describe the operating properties of these indices. RESULTS A total of 53 studies reported on the use of one clinical index [Perianal Disease Activity Index: PDAI], three PROMs, and 10 radiological indices; 25 studies evaluated the operating properties of these indices. The PDAI demonstrated content validity, construct validity, and responsiveness but criterion validity or reliability were not assessed. The Van Assche Index [VAI], modified VAI, and the Magnetic Resonance Index for Assessing Fistulas in Patients with CD [MAGNIFI-CD] were the most studied radiological indices. These indices demonstrated responsiveness and reliability. The VAI and MAGNIFI-CD demonstrated construct validity; criterion and content validity and feasibility have not been assessed. Among the three PROMs, the Crohn's Anal Fistula Quality of Life index demonstrated content and construct validity, inter-observer reliability, and responsiveness; criterion validity, intra-observer reliability, and feasibility have not been assessed for this index. CONCLUSIONS There are no fully valid, reliable, and responsive clinical disease or radiological indices for PFCD. Although the radiological indices demonstrated responsiveness and reliability, well-defined cut-offs for response and remission are lacking. Future research should focus on establishing standardised definitions and thresholds for outcomes.
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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., 100 Dundas street, London, ON, Canada
| | - Virginia Solitano
- Department of Medicine, Division of Gastroenterology, Schulich school of Medicine, Western University, London, ON, Canada
- Alimentiv Inc., 100 Dundas street, London, ON, Canada
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Jurij Hanzel
- Alimentiv Inc., 100 Dundas street, London, ON, Canada
- Faculty of Medicine, University of Ljubljana, Department of Gastroenterology, University Medical Center Ljubljana, Ljubljana, Slovenia
| | | | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Laurent Peyrin Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- Inserm, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada
| | - Christopher Ma
- Alimentiv Inc., 100 Dundas street, London, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Community Health Sciences, Cumming School 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., 100 Dundas street, London, ON, Canada
- Department of Epidemiology and Biostatistics and Robarts Research Institute, Western University, London, ON, Canada
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10
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Schroeder M, Abushamma S, George AT, Balakrishna R, Hickman J, Elumalai A, Wise P, Zulfiqar M, Ludwig DR, Shetty A, Viswanath SE, Luo C, Sebastian S, Ballard DH, Deepak P. Geldof Expert Consensus Classification of Perianal Fistulizing Crohn's Disease: A Real-World Application in a Serial Fistula MRI Cohort. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.02.03.24302160. [PMID: 38352377 PMCID: PMC10863007 DOI: 10.1101/2024.02.03.24302160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2024]
Abstract
Background and Aims Perianal fistulizing Crohn's disease (CD-PAF) is an aggressive phenotype of Crohn's disease (CD) defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by Geldof et al. that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and identify factors that predict transition between classes over time. Methods We identified all patients with CD-PAF and at least one baseline and one follow-up pelvic (pMRI). Geldof Classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs. Results We identified 100 patients with CD-PAF of which 96 were assigned Geldof Classes 1 - 2c at baseline. Most patients (78.1%) started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex (72.0%, 46.6%, 40.0%, p = 0.03) and prior perianal surgery (52.0% vs 44.6% vs 40.0%, p = 0.02) were more frequently observed in those with improved. Baseline pMRI indices were not associated with changes in classification, however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modeling identified only male sex (-0.31, 95% CI -0.60 to -0.02) with improvement in class. Conclusion Geldof classification highlights the dynamic nature of CD-PAF over time, however, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower Geldof classification.
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11
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ten Bokkel Huinink S, Thomassen D, Steyerberg EW, Pauwels RWM, Casanova MJ, Bouguen G, Mak JWY, Molnár T, Lobo AJ, Seidelin JB, Amiot A, D’Haens G, Rivière P, Guidi L, Bor R, Lin WC, Peyrin-Biroulet L, Gisbert JP, Janneke van der Woude C, de Vries AC. Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies. J Crohns Colitis 2024; 18:134-143. [PMID: 37437094 PMCID: PMC10821706 DOI: 10.1093/ecco-jcc/jjad118] [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: 02/13/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. METHODS A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. RESULTS In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. CONCLUSIONS This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.
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Affiliation(s)
| | - Doranne Thomassen
- Leiden UMC, Department of Biomedical Data Sciences, Leiden, The Netherlands
| | - Ewout W Steyerberg
- Leiden UMC, Department of Biomedical Data Sciences, Leiden, The Netherlands
- Erasmus MC, Department of Public Health, Rotterdam, The Netherlands
| | - Renske W M Pauwels
- Erasmus MC, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands
| | - Maria J Casanova
- Hospital Universitario de La Princesa, Department of Gastroenterology, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Guillaume Bouguen
- University Hospital of Pontchaillou, Department of Gastroenterology and Hepatology, Rennes, France
| | - Joyce W Y Mak
- Chinese University of Hong Kong, Department of Medicine and Therapeutics, Hong Kong, Hong Kong
| | - Tamas Molnár
- University of Szeged, First Department of Medicine, Szeged, Hungary
| | - Alan J Lobo
- Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Gastroenterology and Hepatology, Sheffield, UK
| | - Jacob B Seidelin
- Herlev Hospital, Department of Gastroenterology, University of Copenhagen, Denmark
| | - Aurelien Amiot
- Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris Est Creteil University (UPEC), Department of Gastroenterology, Creteil, France
| | - Geert D’Haens
- Amsterdam UMC, Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Pauline Rivière
- Hospitalier Universitaire, Department of Gastroenterology and Hepatology, Bordeaux, France
| | - Luisa Guidi
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Department of Gastroenterology, Rome, Italy
| | - Renata Bor
- University of Szeged, First Department of Medicine, Szeged, Hungary
| | - Wei-Chen Lin
- Mackay Memorial Hospital, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei, Taiwan
| | - Laurent Peyrin-Biroulet
- University Hospital of Nancy, Department of Hepato-Gastroenterology, Vandoeuvre-les-Nancy, France
| | - Javier P Gisbert
- Hospital Universitario de La Princesa, Department of Gastroenterology, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Annemarie C de Vries
- Erasmus MC, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands
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12
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Anandabaskaran S, Hanna L, Iqbal N, Constable L, Tozer P, Hart A. Where Are We and Where to Next?-The Future of Perianal Crohn's Disease Management. J Clin Med 2023; 12:6379. [PMID: 37835022 PMCID: PMC10573672 DOI: 10.3390/jcm12196379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/26/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Perianal fistulizing Crohn's Disease (pCD) affects about 25% of patients with Crohn's Disease (CD). It remains a difficult entity to manage with a therapeutic ceiling of treatment success despite improving medical and surgical management. The refractory nature of the disease calls for an imminent need to better understand its immunopathogenesis and classification to better streamline our treatment options. In this article, we overview the current state of pCD management and discuss where the future of its management may lie.
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Affiliation(s)
- Sulak Anandabaskaran
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales, 390 Victoria Street, Darlinghurst, NSW 2010, Australia
| | - Luke Hanna
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
| | - Nusrat Iqbal
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
| | - Laura Constable
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
| | - Phil Tozer
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
| | - Ailsa Hart
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
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13
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Kim H, Lee DI, Moon SK, Park SJ, You MW. Typical MR features and interpretation of perianal fistulas in patients with Crohn's disease. Eur J Radiol 2023; 167:111046. [PMID: 37634442 DOI: 10.1016/j.ejrad.2023.111046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/05/2023] [Accepted: 08/13/2023] [Indexed: 08/29/2023]
Abstract
Perianal fistulas in Crohn's disease (CD) are a poor prognostic phenotype requiring a combination of medical and surgical management. Perianal fistulas in CD are characterized by more complex and multi-branched fistulas, association with skin tags, and frequent presence of proctitis. A comprehensive approach with clinical examination, endoscopic and MR assessment is required, and in particular, MR interpretation provides detailed information on the type of fistula with its internal component and activity, secondary tracts and extension, internal, external openings, associated abscess, and presence of proctitis. Structured reporting of these items would be recommended for further discussion and management planning both at initial diagnosis and for disease monitoring during treatment follow-up. Management strategy would be individualized for each patient, and control of luminal disease activity could be an important determinant in the selection of treatment options. In this review, we provide an overview of the MRI evaluation of perianal fistulas in CD with a proposed structured MR report.
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Affiliation(s)
- Hyunmin Kim
- Department of Radiology, Kyung Hee University Hospital, Seoul, Republic of Korea
| | - Da In Lee
- Department of Radiology, Kyung Hee University Hospital, Seoul, Republic of Korea
| | - Sung Kyoung Moon
- Department of Radiology, Kyung Hee University Hospital, Seoul, Republic of Korea
| | - Seong Jin Park
- Department of Radiology, Kyung Hee University Hospital, Seoul, Republic of Korea
| | - Myung-Won You
- Department of Radiology, Kyung Hee University Hospital, Seoul, Republic of Korea.
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14
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Jiang J, Cazzetta SE, Athavale A, Kuharic M, Fan T, Silber A, Abilash V, Hadker N, Sharpe E, Nazarey PP. Observational Burden of Illness Study in Patients With Crohn's Disease With and Without Perianal Fistulas in the United States. GASTRO HEP ADVANCES 2023; 2:1066-1076. [PMID: 39131564 PMCID: PMC11307624 DOI: 10.1016/j.gastha.2023.08.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 08/19/2023] [Indexed: 08/13/2024]
Abstract
Background and Aims This study compared disease burden, experiences, and health-related quality of life (HRQoL) between patients with Crohn's perianal fistulas (CPFs) and those with Crohn's disease (CD) without perianal fistulas (PFs; non-PF CD). Methods This cross-sectional, observational study was conducted in 3 cohorts of US patients aged 18-89 years with self-reported, physician-diagnosed CD: (1) non-PF CD; (2) CPF without PF-related surgery; and (3) CPF with PF-related surgery. Data on medical and surgical interventions, CD-specific symptoms, HRQoL (assessed using the Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaires), and fecal incontinence (assessed using Revised Faecal Incontinence Scale and Fecal Incontinence Quality of Life questionnaires) were collected via a web-enabled questionnaire. Results In total, 403 patients with CD completed the questionnaire (non-PF CD, n = 300; CPF without surgery, n = 51; CPF with surgery, n = 52). A high symptom burden was seen across cohorts. More patients with CPF underwent ≥1 CD-related surgery and experienced ≥1 failure of CD-related surgery (79% and 20%) vs non-PF CD (53% and 9%; P < .001). Overall HRQoL outcomes were worse for patients with CPF vs non-PF CD, with significantly worse Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaire scores for those without PF-related surgery (P < .01). Across all cohorts, 58% of patients reported experiencing fecal incontinence, which had a greater negative impact (higher Revised Faecal Incontinence Scale scores; lower Fecal Incontinence Quality of Life scores) in patients with CPF vs non-PF CD. Conclusion Patients with CPF experience substantial HRQoL burden, reflecting the impact of symptoms and medical/surgical interventions. These results may help to inform comprehensive care strategies to improve patient HRQoL.
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Affiliation(s)
- Jeanne Jiang
- Takeda Pharmaceuticals USA, Inc., Lexington, Massachusetts
| | | | | | - Maja Kuharic
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois, Chicago, Illinois
| | - Tao Fan
- Takeda Pharmaceuticals USA, Inc., Lexington, Massachusetts
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15
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Meima - van Praag EM, Becker MA, van Rijn KL, Wasmann KA, Stoker J, D'Haens GR, Ponsioen CY, Gecse KB, Dijkgraaf MG, Spinelli A, Danese S, Bemelman WA, Buskens CJ. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy alone for Crohn's perianal fistulas (PISA-II): long-term outcomes of an international, multicentre patient preference, randomised controlled trial. EClinicalMedicine 2023; 61:102045. [PMID: 37457118 PMCID: PMC10344824 DOI: 10.1016/j.eclinm.2023.102045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 05/30/2023] [Accepted: 05/30/2023] [Indexed: 07/18/2023] Open
Abstract
Background The PISA-II trial showed that short-term anti-tumour necrosis factor (anti-TNF) therapy followed by surgical closure induces radiological healing of perianal fistulas in patients with Crohn's disease more frequently than anti-TNF therapy alone after 18 months. This study aimed to compare long-term outcomes of both treatment arms. Methods Follow-up data were collected from patients who participated in the PISA-II trial, an international patient preference randomised controlled trial. This multicentre trial was performed in nine hospitals in the Netherlands and one hospital in Italy. Patients with Crohn's disease above the age of 18 years with an active high perianal fistula and a single internal opening were asked to participate. Patients were allocated to anti-TNF therapy (intravenous infliximab, or subcutaneous adalimumab, at the discretion of the gastroenterologist) for one year, or surgical closure combined with 4-months anti-TNF therapy. Patients without a treatment preference were randomised (1:1) using random block randomisation (block sizes of six without stratification), and patients with a treatment preference were treated according to their preferred treatment arm. For the current follow-up study, data were collected until May 2022. Primary outcome was radiological healing on magnetic resonance imaging (MRI), including all participants with a MRI made less than 6 months ago at the time of data collection. Analysis was based on observed data. Findings Between September 14, 2013, and December 7, 2019, 94 patients were enrolled in the trial. Long-term follow-up data were available in 91 patients (36/38 (95%) anti-TNF + surgical closure, 55/56 (98%) anti-TNF). A total of 14/36 (39%) patients in the surgical closure arm were randomly assigned, which was not significantly different in the anti-TNF treatment arm (16/55 (29%) randomly assigned). Median follow-up was 5.7 years (interquartile range (IQR) 5-7). Radiological healing occurred significantly more often after anti-TNF + surgical closure (15/36 = 42% versus 10/55 = 18%; P = 0.014). Clinical closure was comparable (26/36 = 72% versus 34/55 = 62%; P = 0.18) in both groups. However, clinical closure in the surgical group was achieved with less re-interventions 4/26 (= 15%) versus 18/34 (= 53%), including (redo-)surgical closure procedures. Recurrences occurred in 0/25 (0%) patients with radiological healing versus 27/76 (36%) patients with clinical closure, sometime during follow-up. Anti-TNF trough levels were higher in patients with long-term clinical closure in both groups (P = 0.031 and P = 0.014). In 6/11 (55%) patients in the anti-TNF group with available trough levels, recurrences were diagnosed within three months of a drop under 3.5ug/ml. 36 patients stopped anti-TNF, after which 0/14 (0%) patients with radiological healing developed a recurrence and 9/22 (41%) with clinical closure. Self-rated (in)continence was comparable between groups, and 79% (60/76) of patients indicated comparable/improved continence after treatment. Decision-regret analysis showed that all (30/30) anti-TNF + surgical closure patients agreed or strongly agreed that surgery was the right decision versus 78% (36/46) in the anti-TNF arm. All surgical closure patients would go for the same treatment again, whereas this was 89% (41/46) in the anti-TNF arm. Interpretation This study confirmed that surgical closure should be considered in amenable patients with perianal fistulas and Crohn's disease as long-term outcomes were favourable, and that radiological healing should be the aim of treatment as recurrences only occurred in patients without radiological healing. In patients with complete MRI closure, anti-TNF could be safely stopped. Funding None.
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Affiliation(s)
- Elise M. Meima - van Praag
- Department of Surgery, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
| | - Marte A.J. Becker
- Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Kyra L. van Rijn
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Karin A.T.G.M. Wasmann
- Department of Surgery, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, 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
| | - Geert R.A.M. D'Haens
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
| | - Cyriel Y. Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
| | - Krisztina B. Gecse
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
| | - Marcel G.W. Dijkgraaf
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Meibergdreef 9, Amsterdam, the Netherlands
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Willem A. Bemelman
- Department of Surgery, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
- Department of Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Christianne J. Buskens
- Department of Surgery, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
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16
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Kim MJ. [Perianal Fistula: An Overview]. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2023; 84:565-585. [PMID: 37325009 PMCID: PMC10265243 DOI: 10.3348/jksr.2023.0018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 05/04/2023] [Accepted: 05/09/2023] [Indexed: 06/17/2023]
Abstract
Perianal fistula is a common inflammatory condition in the general population and affects the area around the anal canal. Although most cases are benign, they cause serious morbidity and require surgical treatment due to a high risk of recurrence. MR imaging is a gold standard technique for the evaluation of perianal fistulas and provides accurate information on the anatomy of the anal canal, its relationship to the anal sphincter complex, accurate identification of secondary tracts or abscesses, and reporting associated complications. MR imaging can help monitor treatment effects and determine treatment methods. Crohn's disease-related fistulas often require medical rather than surgical treatment. The radiologist is required to know the anatomy and MR imaging findings of the perianal fistula to present an accurate diagnosis to the clinician.
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Nakase H, Esaki M, Hirai F, Kobayashi T, Matsuoka K, Matsuura M, Naganuma M, Saruta M, Tsuchiya K, Uchino M, Watanabe K, Hisamatsu T. Treatment escalation and de-escalation decisions in Crohn's disease: Delphi consensus recommendations from Japan, 2021. J Gastroenterol 2023; 58:313-345. [PMID: 36773075 PMCID: PMC10050046 DOI: 10.1007/s00535-023-01958-z] [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: 09/29/2022] [Accepted: 01/08/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn's disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD. METHODS PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021. RESULTS Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD. CONCLUSIONS These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.
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Affiliation(s)
- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-Ku, Sapporo, Hokkaido 060-8543 Japan
| | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611 Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Motoi Uchino
- Division of Inflammatory Bowel Disease, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Hyogo Japan
| | - Kenji Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Hyogo Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611 Japan
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18
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Meima-van Praag EM, van Rijn KL, Wasmann KATGM, Snijder HJ, Stoker J, D'Haens GR, Gecse KB, Gerhards MF, Jansen JM, Dijkgraaf MGW, van der Bilt JDW, Mundt MW, Spinelli A, Danese S, Bemelman WA, Buskens CJ. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial. Lancet Gastroenterol Hepatol 2022; 7:617-626. [PMID: 35427495 DOI: 10.1016/s2468-1253(22)00088-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 03/07/2022] [Accepted: 03/08/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone. METHODS The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion. FINDINGS Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment. INTERPRETATION Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach. FUNDING Netherlands Organisation for Health Research and Development and Broad Medical Research Program.
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Affiliation(s)
- Elise M Meima-van Praag
- Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Kyra L van Rijn
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Karin A T G M Wasmann
- Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Harmanna J Snijder
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Geert R D'Haens
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Krisztina B Gecse
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Michael F Gerhards
- Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
| | - Jeroen M Jansen
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
| | - Marcel G W Dijkgraaf
- Department of Epidemiology and Data Science, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | | | - Marco W Mundt
- Department of Gastroenterology and Hepatology, Flevoziekenhuis, Almere, Netherlands
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Willem A Bemelman
- Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands; Department of Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Christianne J Buskens
- Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
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19
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Iqbal N, Sackitey C, Gupta A, Tolan D, Plumb A, Godfrey E, Grierson C, Williams A, Brown S, Maxwell-Armstrong C, Anderson I, Selinger C, Lobo A, Hart A, Tozer P, Lung P. The development of a minimum dataset for MRI reporting of anorectal fistula: a multi-disciplinary, expert consensus process. Eur Radiol 2022; 32:8306-8316. [PMID: 35732929 DOI: 10.1007/s00330-022-08931-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 05/08/2022] [Accepted: 05/30/2022] [Indexed: 11/27/2022]
Abstract
There are a range of sphincter-preserving procedures available to treat anorectal fistula, some of which can be precluded, or rendered more optimal by specific features of fistula anatomy. Magnetic resonance imaging (MRI) is the gold standard modality for assessing anorectal fistula. To maximise clinical utility, the MRI report should accurately describe these clinically relevant features. We aimed to develop a minimum dataset for reporting MRI of anorectal fistula, in order to improve the assessment and management of these patients. A longlist of 70 potential items for the minimum dataset was generated through systematic review of the literature. This longlist was presented to radiologists, surgeons and gastroenterologists in an online survey to understand the features that shape current clinical practice. The longlist and survey results were then presented to an expert consensus panel to generate the final minimum dataset through discussion and anonymous voting. The final minimum dataset details the general characteristics, features of the internal and external openings, path of the fistula through the sphincters and any associated extensions and collections that should be described in all MRI reports for anal fistula. Additional surgical and perianal Crohn's disease subsets were developed to indicate the features that aid decision-making for these patients, in addition to a minimum dataset for the clinical request. This study represents a multi-disciplinary approach to developing a minimum dataset for MRI reporting of anal fistula, highlighting the most important features to report that can assist in clinical decision-making. KEY POINTS: • This paper recommends the minimum features that should be included in all MRI reports for the assessment of anal fistula, including Parks classification, number of tracts, features of the internal and external opening, path of the tract through the sphincters, the presence and features of extensions and collections. • Additional features that aid decision-making for surgery or in the presence of Crohn's disease have been identified. • The items that should be included when requesting an MRI are specified.
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Affiliation(s)
- Nusrat Iqbal
- Robin Phillips' Fistula Research Unit, St Mark's Hospital, London, UK
| | - Charlene Sackitey
- Robin Phillips' Fistula Research Unit, St Mark's Hospital, London, UK
| | | | | | | | | | | | - Andrew Williams
- Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK
| | - Steven Brown
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | | | | | | | - Alan Lobo
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Ailsa Hart
- Robin Phillips' Fistula Research Unit, St Mark's Hospital, London, UK
| | - Phil Tozer
- Robin Phillips' Fistula Research Unit, St Mark's Hospital, London, UK
| | - Phillip Lung
- Robin Phillips' Fistula Research Unit, St Mark's Hospital, London, UK.
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20
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Choshen S, Turner D, Pratt LT, Precel R, Greer ML, Castro DA, Assa A, Martínez-León MI, Herman-Sucharska I, Coppenrath E, Konen O, Davila J, Bekhit E, Alsabban Z, Focht G, Gavish M, Griffiths A, Cytter-Kuint R. Development and Validation of a Pediatric MRI-Based Perianal Crohn Disease (PEMPAC) Index-A Report from the ImageKids Study. Inflamm Bowel Dis 2022; 28:700-709. [PMID: 34151950 DOI: 10.1093/ibd/izab147] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND As part of the prospective multicenter ImageKids study, we aimed to develop and validate the pediatric MRI-based perianal Crohn disease (PEMPAC) index. METHODS Children with Crohn disease with any clinical perianal findings underwent pelvic magnetic resonance imaging at 21 sites globally. The site radiologist and 2 central radiologists provided a radiologist global assessment (RGA) on a 100 mm visual analog scale and scored the items selected by a Delphi group of 35 international radiologists and a review of the literature. Two weighted multivariable statistical models were constructed against the RGA. RESULTS Eighty children underwent 95 pelvic magnetic resonance imaging scans; 64 were used for derivation and 31 for validation. The following items were included: fistula number, location, length and T2 hyperintensity; abscesses; rectal wall involvement; and fistula branching. The last 2 items had negative beta scores and thus were excluded in a contending basic model. In the validation cohort, the full and the basic models had the same strong correlation with the RGA (r = 0.75; P < 0.01) and with the adult Van Assche index (VAI; r = 0.93 and 0.92; P < 0.001). The correlation of the VAI with the RGA was similar (r = 0.77; P < 0.01). The 2 models and the VAI had a similar ability to differentiate remission from active disease (area under the receiver operating characteristic curve, 0.91-0.94). The PEMPAC index had good responsiveness to change (area under the receiver operating characteristic curve, 0.89; 95% confidence interval, 0.69-1.00). CONCLUSIONS Using a blended judgmental and mathematical approach, we developed and validated an index for quantifying the severity of perianal disease in children with CD. The adult VAI may also be used with confidence in children.
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Affiliation(s)
- Sapir Choshen
- Pediatric Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Dan Turner
- The Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel.,Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Li-Tal Pratt
- Pediatric Imaging Unit, Imaging Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ronit Precel
- Pediatric Imaging Unit, Imaging Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Mary-Louise Greer
- Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada.,Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Denise A Castro
- Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada.,Department of Diagnostic Radiology, Kingston Health Science Centre, Queen's University, Kingston, Canada
| | - Amit Assa
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Diagnostic Imaging, Schneider Children's Hospital, Petach-Tikva, Israel
| | | | | | | | - Osnat Konen
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Diagnostic Imaging, Schneider Children's Hospital, Petach-Tikva, Israel
| | - Jorge Davila
- Department of Medical Imaging, Children's Hospital of Eastern Ontario, Ottawa, Canada
| | - Elhamy Bekhit
- Department of Medicine and Radiology, The Royal Children's Hospital, Melbourne, Australia
| | - Zehour Alsabban
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Gili Focht
- The Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Matan Gavish
- School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel
| | - Anne Griffiths
- Department of Gastroenterology, Hospital for Sick Children, University of Toronto, Canada
| | - Ruth Cytter-Kuint
- Radiology Department, Shaare Zedek Medical Center, Jerusalem, Israel
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21
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Greer MLC, Taylor SA. Perianal Imaging in Crohn Disease: Current Status With a Focus on MRI, From the AJR Special Series on Imaging of Inflammation. AJR Am J Roentgenol 2022; 218:781-792. [PMID: 34549607 DOI: 10.2214/ajr.21.26615] [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: 11/18/2022]
Abstract
Fistulizing perianal disease, a frequent, chronic, and often debilitating manifestation of Crohn disease (CD) in adults and children, has been relatively refractory to treatment in the past. The advent of biologic agents such as anti-tumor necrosis factor-α and cellular therapies, used in conjunction with a range of surgical interventions, has greatly improved disease outcomes, although complete remission can still be elusive. This Special Series review considers current perianal imaging options, specifically pelvic MRI and endoanal and transperineal ultrasound, as well as their roles in the diagnosis, management, and assessment of treatment response. Pelvic MRI is the first-line modality for imaging perianal CD, given the complexity of fistulas encountered in CD. MRI technical acquisition parameters for adults and children and an approach to MRI interpretation and reporting are provided. Anatomic classification systems for fistulizing peri-anal disease are presented. We also explore the history, current landscape, and future developments of MRI features of perianal disease as imaging biomarkers, to quantify activity and severity and to consider CD MRI-based inflammatory activity scores. We discuss the reliability and validation of a number of indexes (including the pediatric MRI-based perianal CD [PEMPAC] index, the MR novel index for fistula imaging in CD [MAGNIFI-CD], the Van Assche index, and the modified Van Assche index), their potential to quantify treatment response, and possible prognostic capabilities.
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Affiliation(s)
- Mary-Louise C Greer
- Department of Diagnostic Imaging, The Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada
- Department of Medical Imaging, University of Toronto, Toronto, ON, Canada
| | - Stuart A Taylor
- Center for Medical Imaging, University College London, London, United Kingdom
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22
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Queiroz NSF, Garcia KS, Miranda EF, Kotze PG. Patient-Reported Outcomes Measures in Perianal Fistulizing Crohn's Disease. Rev Recent Clin Trials 2022; 17:RRCT-EPUB-122860. [PMID: 35469573 DOI: 10.2174/1574887117666220425125424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 01/06/2022] [Accepted: 01/10/2022] [Indexed: 06/14/2023]
Abstract
Perianal fistulizing Crohn's disease (PFCD) is a disabling complication of Crohn's disease (CD) that can significantly impact on patients' quality of life (QoL) and often requires multidisciplinary care. Clinical trials assessing the efficacy of medical and surgical interventions for fistulas usually evaluate outcomes such as closure of fistula tracts or radiologic healing. However, these traditional outcome assessments fail in capturing the impact of the disease from patients' perspectives. In this context, regulatory authorities have increasingly encouraged the inclusion of validated patient-reported outcomes (PRO) that assess disease activity and reveal how a patient functions and feels. This recent trend towards patient-centered care aims to ensure that improvements in efficacy outcomes are accompanied by meaningful benefits to patients. The aim of this review is to discuss currently available PRO measures (PROMS) for the assessment of PFCD to provide to physicians appropriate tools aiming to optimize patient care and disseminate the use of these instruments in clinical practice.
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Affiliation(s)
| | - Karoline Soares Garcia
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Eron Fabio Miranda
- Colorectal Surgery Unit, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
| | - Paulo Gustavo Kotze
- Colorectal Surgery Unit, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
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23
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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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24
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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] [MESH Headings] [Grants] [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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Adegbola SO, Sahnan K, Tozer P, Warusavitarne J. Emerging Data on Fistula Laser Closure (FiLaC) for the Treatment of Perianal Fistulas; Patient Selection and Outcomes. Clin Exp Gastroenterol 2021; 14:467-475. [PMID: 34908858 PMCID: PMC8664604 DOI: 10.2147/ceg.s269464] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 11/22/2021] [Indexed: 12/14/2022] Open
Abstract
Fistula laser closure (FiLaC) is a relatively new sphincter-sparing technique in fistula surgery that was initially reported in 2011. It involves the radial dissipation of laser energy in the fistula tract and, through a combination of coagulation and shrinkage of the tract, is proposed to result in progressive sealing of fistulas. Early studies have suggested minimal impact on continence and touted the advantage of minimal morbidity with potential of repeat procedures if the technique fails initially. Despite early promising results, ten years on, questions remain on the technique, patient selection and long-term outcomes. This narrative review assesses the evidence reported to-date of radially emitting laser fistula surgery in the treatment of perianal fistulas.
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Affiliation(s)
- Samuel O Adegbola
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Harrow, UK.,Department of Surgery and Cancer, Imperial College, London, UK
| | - Kapil Sahnan
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Harrow, UK.,Department of Surgery and Cancer, Imperial College, London, UK
| | - Phillip Tozer
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Harrow, UK.,Department of Surgery and Cancer, Imperial College, London, UK
| | - Janindra Warusavitarne
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Harrow, UK.,Department of Surgery and Cancer, Imperial College, London, UK
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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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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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Garg P, Yagnik VD, Kaur B, Menon GR, Dawka S. Role of MRI to confirm healing in complex high cryptoglandular anal fistulas: long-term follow-up of 151 cases. Colorectal Dis 2021; 23:2447-2455. [PMID: 33900011 DOI: 10.1111/codi.15695] [Citation(s) in RCA: 4] [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: 01/10/2021] [Revised: 03/01/2021] [Accepted: 04/19/2021] [Indexed: 12/23/2022]
Abstract
AIM Complex fistula-in-ano can recur even after complete clinical healing has occurred. 'Radiological healing' of fistula on MRI correlates well with long-term healing rates but no study has yet objectively quantified this. The aim of this study was to assess the accuracy of anal fistula healing as documented on MRI and to correlate it with long-term healing as evidenced on long-term follow-up. METHODS Patients with clinically healed anal fistulas who also had radiological healing checked by postoperative MRI were included in the study. RESULTS Three hundred and twenty-five patients operated for high complex fistula-in-ano were followed up for 14-68 months (median 38 months). Postoperative MRI was done to assess radiological healing of the fistula in 151 patients, and they were included in the study. The mean age was 39.4 ± 10.5 years (116 men). Five patients were lost to follow-up. The fistulas did not heal radiologically (on MRI) in 20 patients and recurred in all these patients. The fistulas healed radiologically (on MRI) in 126 patients. On long-term follow-up, 124/126 patients remained healed while 2/126 had a recurrence. In the first patient, the fistula recurred 40 months after complete radiological healing. In the second patient, the fistula recurred 10 months after complete radiological healing but pus from the fistula tested positive for tuberculosis (by real-time polymerase chain reaction) and he was excluded from the analysis. Thus, there was only one (1/125) recurrence on long-term follow-up. CONCLUSIONS Radiological healing on MRI correlates well with long-term healing in complex fistula-in-ano.
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Affiliation(s)
- Pankaj Garg
- Indus Super Specialty Hospital, Mohali, India
- Garg Fistula Research Institute, Panchkula, India
| | - Vipul D Yagnik
- Nishta Surgical Hospital and Research Centre, Patan, India
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Adegbola SO, Dibley L, Sahnan K, Wade T, Verjee A, Sawyer R, Mannick S, McCluskey D, Bassett P, Yassin N, Warusavitarne J, Faiz O, Phillips R, Tozer PJ, Norton C, Hart AL. Development and initial psychometric validation of a patient-reported outcome measure for Crohn's perianal fistula: the Crohn's Anal Fistula Quality of Life (CAF-QoL) scale. Gut 2021; 70:1649-1656. [PMID: 33272978 PMCID: PMC8355881 DOI: 10.1136/gutjnl-2019-320553] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 08/22/2020] [Accepted: 10/29/2020] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Crohn's perianal fistulas are challenging for patients and clinicians. Many do not respond to available treatments and despite recommendations by a global consensus, there are currently no specific patient-derived quality of life tools to measure response to treatment. We present a new validated patient-reported outcome measure (PROM) for this complicated disease phenotype. METHODS A draft questionnaire was generated using unstructured qualitative patient interviews on the experience of living with Crohn's perianal fistula, a nationwide multidisciplinary consensus exercise, a systematic review of outcomes assessing medical/surgical/combined treatment and a patient and public involvement day. Psychometric properties were assessed including construct validity (by comparison with the Hospital Anxiety and Depression Scale (HADS) and the UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ)), and reliability and responsiveness was assessed by test-retest analysis. RESULTS Data from 211 patients contributed to development of a final 28-item questionnaire. The Crohn's Anal Fistula Quality of Life (CAF-QoL) demonstrated good internal consistency (Cronbach's alpha 0.88), excellent stability (intraclass correlation 0.98) and good responsiveness and construct validity, with positive correlation with the UK-IBDQ and HADS. CONCLUSION The CAF-QoL scale is ready for use as a PROM in research and clinical practice. It complements objective clinical evaluation of fistula by capturing impact on the patient.
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Affiliation(s)
- Samuel O Adegbola
- Surgery and Cancer, Imperial College London, London, UK .,Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
| | - Lesley Dibley
- Faculty of Education, Health and Human Sciences, University of Greenwich, London, UK
| | - Kapil Sahnan
- Surgery and Cancer, Imperial College London, London, UK,Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
| | - Tiffany Wade
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK
| | - Azmina Verjee
- CAF-QoL Patient and Public Involvement Team, London, UK
| | - Rachel Sawyer
- CAF-QoL Patient and Public Involvement Team, London, UK
| | | | | | - Paul Bassett
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
| | - Nuha Yassin
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
| | - Janindra Warusavitarne
- Surgery and Cancer, Imperial College London, London, UK,Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
| | - Omar Faiz
- Surgery and Cancer, Imperial College London, London, UK,Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
| | - Robin Phillips
- Surgery and Cancer, Imperial College London, London, UK,Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
| | - Phil J Tozer
- Surgery and Cancer, Imperial College London, London, UK,Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
| | - Christine Norton
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK
| | - Ailsa L Hart
- Surgery and Cancer, Imperial College London, London, UK,Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, London, UK
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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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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: 4] [Impact Index Per Article: 1.0] [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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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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Heterogeneity in outcome selection, definition and measurement in studies assessing the treatment of cryptoglandular anal fistula: findings from a systematic review. Tech Coloproctol 2021; 25:761-830. [PMID: 33963945 PMCID: PMC8187216 DOI: 10.1007/s10151-021-02452-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 04/15/2021] [Indexed: 12/12/2022]
Abstract
Background Treatment for cryptoglandular anal fistula (AF) is challenging and a lack of uniform outcomes in the literature prevents direct comparison of treatments. This can be addressed by developing a core outcome set, a standardised set of outcomes reported in all interventional studies for a specific condition. The aim of this systematic review is to assess the range of outcomes, their definitions, and the measurement instruments currently utilised in interventional studies for adult patients with AF. This will inform the development of an AF core outcome set. Methods Medline, Embase and The Cochrane Library were searched to identify all patient- and clinician-reported outcomes in studies assessing medical, surgical or combination treatment of adult patients with AF published from January 2008 to May 2020. The resulting outcomes were categorized according to the Core Outcome Measurement in Effectiveness Trials (COMET) taxonomy to better understand their distribution. Results In total, 155 studies were included, 552 outcomes were extracted, with a median of three outcomes (interquartile range 2–5) per study. Only 25% of studies demonstrated high-quality outcome reporting. The outcomes were merged into 52 unique outcomes and structured into four core areas and 14 domains, with the majority in the domain of physiological or clinical (gastrointestinal) outcomes. The most commonly reported outcomes were healing (77%), incontinence (63%), and recurrence (40%), with no single outcome assessed across all studies. There was a wide variation in outcome definitions and measurement instruments used. Conclusions There is substantial heterogeneity in outcomes, definitions, and measurement instruments reported in interventional studies for cryptoglandular anal fistula. This emphasises the need for standardised outcome reporting and measurement.
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Hashash JG, Mourad FH. Perianal Fistulizing Crohn's Disease: No Shortcuts to a Deep Understanding of the Disease. Dig Dis Sci 2021; 66:1392-1393. [PMID: 32833159 DOI: 10.1007/s10620-020-06549-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Jana G Hashash
- Division of Gastroenterology, American University of Beirut, Beirut, Lebanon.
| | - Fadi H Mourad
- Division of Gastroenterology, American University of Beirut, Beirut, Lebanon
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Effectiveness of Infliximab on Deep Radiological Remission in Chinese Patients with Perianal Fistulizing Crohn's Disease. Dig Dis Sci 2021; 66:1658-1668. [PMID: 32524415 DOI: 10.1007/s10620-020-06398-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 06/03/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Information concerning deep radiological healing of perianal fistulas in Chinese patients with CD is limited. The present study aimed to establish the effectiveness of infliximab on CD-related perianal fistulas using magnetic resonance imaging (MRI) and identify predictors of deep radiological remission of fistulas. METHODS We retrospectively reviewed patients with CD with draining perianal fistulas treated with infliximab and included only those who underwent clinical assessment and MRI before and after infliximab therapy. RESULTS Among 178 patients who underwent repeated MRI and clinical assessment, 65.2% had complex fistulas. Post-infliximab therapy, 55.1% of patients with perianal fistulizing CD showed clinical remission and 26.4% presented a clinical response; 38.2% had deep radiological remission, and 34.3% had a partial response based on the Ng score; the Van Assche scores decreased obviously compared with baseline. Prolonged infliximab infusion (18 times) presented higher radiological remission rates in patients with CD with complex fistulas. Concomitant treatment with azathioprine increased the fistula healing rate compared with infliximab alone (50% vs. 36.9%, P < 0.001). Younger age at diagnosis of CD, proctitis and requiring perianal surgery were identified as predictors of poor deep radiological remission of fistulas. Eight of ten patients who stopped infliximab and switched to an alternative agent retained a status of fistula healing in the first year of follow-up. CONCLUSIONS Infliximab induced deep radiological remission of perianal fistulas in Chinese patients with CD. Routine MRI should be used to monitor fistula healing. Patients with younger age at diagnosis of CD, proctitis, and/or requiring perianal surgery should receive combined therapy and careful monitoring.
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Cao WT, Huang R, Jiang KF, Qiao XH, Wang JJ, Fan YH, Xu Y. Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review. World J Gastroenterol 2021; 27:886-907. [PMID: 33727776 PMCID: PMC7941861 DOI: 10.3748/wjg.v27.i9.886] [Citation(s) in RCA: 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: 10/17/2020] [Revised: 12/25/2020] [Accepted: 01/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.
AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.
METHODS We searched PubMed/MEDLINE, Embase, and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.
RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6 μg/mL in IBD. Blood concentration of infliximab reaching 5.0-12.7 μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease. Blood concentration of adalimumab reaching 7.2-16.2 μg/mL or more could predict mucosal healing in IBD. The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8 μg/mL in perianal fistulizing Crohn's disease. Blood concentration of vedolizumab surpassing 25.0 μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 μg/mL.
CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies, whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.
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Affiliation(s)
- Wan-Ting Cao
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Rong Huang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Ke-Fang Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Xue-Hui Qiao
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Jing-Jing Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Yi-Hong Fan
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Yi Xu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
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Lee JL, Yoon YS, Yu CS. Treatment Strategy for Perianal Fistulas in Crohn Disease Patients: The Surgeon's Point of View. Ann Coloproctol 2021; 37:5-15. [PMID: 33730796 PMCID: PMC7989558 DOI: 10.3393/ac.2021.02.08] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 02/08/2021] [Indexed: 12/12/2022] Open
Abstract
Perianal fistula is a frequent complication and one of the subclassifications of Crohn disease (CD). It is the most commonly observed symptomatic condition by colorectal surgeons. Accurately classifying a perianal fistula is the initial step in its management in CD patients. Surgical management is selected based on the type of perianal fistula and the presence of rectal inflammation; it includes fistulotomy, fistulectomy, seton procedure, fistula plug insertion, video-assisted ablation of the fistulous tract, stem cell therapy, and proctectomy with stoma creation. Perianal fistulas are also managed medically, such as antibiotics, immunomodulators, and biologics including anti-tumor necrosis factor-alpha agents. The current standard treatment of choice for perianal fistula in CD patients is the multidisciplinary approach combining surgical and medical management; however, the rate of long-term remission is low and is reported to be 50% at most. Therefore, the optimum management strategy for perianal fistulas associated with CD remains controversial. Currently, the goal of management for CD-related perianal fistulas are controlling symptoms and maintaining long-term anal function without proctectomy, while monitoring progression to anorectal carcinoma. This review evaluates perianal fistula in CD patients and determines the optimal surgical management strategy based on recent evidence.
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Affiliation(s)
- Jong Lyul Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Sik Yoon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Sik Yu
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Meima ‐ van Praag EM, van Rijn KL, Monraats MA, Buskens CJ, Stoker J. Magnetic resonance imaging after ligation of the intersphincteric fistula tract for high perianal fistulas in Crohn's disease: a retrospective cohort study. Colorectal Dis 2021; 23:169-177. [PMID: 32767809 PMCID: PMC7891352 DOI: 10.1111/codi.15296] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 07/28/2020] [Indexed: 12/16/2022]
Abstract
AIM Ligation of the intersphincteric fistula tract (LIFT) is increasingly being used for surgical closure of high perianal fistulas in Crohn's disease. Currently, data on postoperative MRI findings are scarce, although they are considered important for assessing healing and recurrence. Our aim, therefore, was to evaluate fistula characteristics on MRI and their relationship with clinical outcomes after LIFT. METHOD Consecutive Crohn's patients treated with LIFT between 2007 and 2018 who underwent baseline and follow-up MRI were retrospectively included. MRIs were scored by two radiologists according to characteristics based on the original and modified Van Assche indices. MRI findings, with emphasis on fibrosis, and the relationship with clinical healing, re-interventions and recurrences are described. RESULTS Twelve patients were included [four men, median age 34 (interquartile range 28-39) years]. Follow-up MRI was performed at a median of 5.5 months (interquartile range 2.5-6.0) after LIFT. At baseline, all patients showed a tract with predominantly granulation tissue, which changed to predominantly fibrotic in seven (in three of whom it was completely fibrotic). All patients with a (predominantly) fibrotic tract had clinical closure and no re-interventions or recurrences during long-term follow-up. In contrast, of the five patients with persisting granulation tissue, two reached clinical healing, two needed re-intervention and one had a recurrence. CONCLUSION Markedly decreased fistula activity can be observed on MRI after LIFT. The majority of patients develop a predominantly fibrotic tract relatively soon after LIFT without clinical recurrence, suggesting a highly effective therapy. Unfavourable clinical outcomes were only present in patients with persisting granulation tissue, indicating the potential prognostic value of MRI.
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Affiliation(s)
- E. M. Meima ‐ van Praag
- Department of SurgeryAmsterdam Gastroenterology, Endocrinology and MetabolismAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
| | - K. L. van Rijn
- Department of Radiology and Nuclear MedicineAmsterdam Gastroenterology, Endocrinology and MetabolismAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
| | - M. A. Monraats
- Department of Radiology and Nuclear MedicineAmsterdam Gastroenterology, Endocrinology and MetabolismAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
| | - C. J. Buskens
- Department of SurgeryAmsterdam Gastroenterology, Endocrinology and MetabolismAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
| | - J. Stoker
- Department of Radiology and Nuclear MedicineAmsterdam Gastroenterology, Endocrinology and MetabolismAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
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Lee T, Kamm MA, Bell S, Lust M, Brown S, Niewiadomski O, Basnayake C, Wright E, D'Souza B, Woods R, Wei SC, Connell W, Thompson A, Yong E, Ding NS. Long-term outcomes of perianal fistulizing Crohn's disease in the biologic era. JGH OPEN 2020; 5:235-241. [PMID: 33553661 PMCID: PMC7857282 DOI: 10.1002/jgh3.12475] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/21/2020] [Accepted: 11/30/2020] [Indexed: 11/08/2022]
Abstract
Background and Aim While the advent of biologic therapy has led to improved outcomes in perianal fistulizing Crohn's disease (pfCD), loss of response is common. Previous studies suggest that patients who achieve radiological healing (with healing of underlying tracts on magnetic resonance imaging [MRI]) have a longer duration of response. The aim of this study was to characterize MRI outcomes of pfCD at a specialist inflammatory bowel disease (IBD) unit and compare the long-term clinical outcomes between patients achieving MRI and clinical healing. Methods A retrospective analysis of perianal fistulizing Crohn's patients treated at one specialist IBD unit was performed. Records were reviewed for patient demographics, disease history, clinical assessments, investigation results, and disease flares. Clinical remission was defined as closure of all baseline fistula openings. Radiological healing was defined as the absence of any T2-hyperintense sinuses, tracts, or collections. The primary end-point was rate of MRI healing. The secondary outcome was defined as flare-free period (time between clinical or radiological healing and patients' first signs/symptoms requiring therapy escalation). Results A total of 93 patients were included, with a median follow-up of 4.8 years (interquartile range, 2.4-6 years). Of 44 patients, 22 (50%) achieved clinical remission, while 15 of 93 (16%) achieved radiological healing. Of 22 patients, 10 (45%) with clinical remission had a subsequent disease flare (median time of 7 months) compared with 3 of 15 (20%) patients with MRI healing (median time of 3.6 years). Radiological healing was associated with a significantly longer flare-free period (P = 0.01). Conclusion Radiological healing occurs less commonly but represents a deeper form of healing, associated with improved long-term clinical outcomes.
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Affiliation(s)
- Tanya Lee
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Michael A Kamm
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Sally Bell
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Mark Lust
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Steve Brown
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Ola Niewiadomski
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Chamara Basnayake
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Emily Wright
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Basil D'Souza
- Department of Colorectal Surgery St Vincent's Hospital Melbourne Victoria Australia
| | - Rodney Woods
- Department of Colorectal Surgery St Vincent's Hospital Melbourne Victoria Australia
| | - Shu Chen Wei
- Department of Internal Medicine National Taiwan University Hospital and College of Medicine Taipei Taiwan
| | - William Connell
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Alexander Thompson
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
| | - Eric Yong
- Department of Radiology St Vincent's Hospital Melbourne Victoria Australia
| | - Nik Sheng Ding
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.,Department of Medicine University of Melbourne Melbourne Victoria Australia
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Adegbola SO, Dibley L, Sahnan K, Wade T, Verjee A, Sawyer R, Mannick S, McCluskey D, Yassin N, Phillips RKS, Tozer PJ, Norton C, Hart AL. Burden of disease and adaptation to life in patients with Crohn's perianal fistula: a qualitative exploration. Health Qual Life Outcomes 2020; 18:370. [PMID: 33218361 PMCID: PMC7678264 DOI: 10.1186/s12955-020-01622-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 11/06/2020] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Perianal fistulas are a challenging manifestation of Crohn's disease. Best medical and surgical therapy results in only about a third of patients remaining in remission at one year on maintenance treatment and sustained healing is often elusive. There is little published data on patient perspective of living with the condition or coping strategies in the face of non-curative/non-definitive treatment. We aimed to understand the experience of living with perianal fistula(s) and their impact on quality of life and routine functioning. METHODS This exploratory qualitative study used purposive sampling to recruit participants with current / previous diagnosis of Crohn's anal fistulas, from national IBD / bowel disease charities. The "standards for reporting qualitative research" (SRQR) recommendations were followed. Unstructured individual face-to-face interviews were audio recorded, transcribed and analysed thematically. Early themes were reviewed by the study team including patient advocates, clinicians and qualitative researchers. RESULTS Twelve interviews were conducted, achieving apparent data saturation. Three broad themes were uncovered: Burden of symptoms; Burden of treatment; and Impact on emotional, physical and social well-being. Each included several sub-themes, with considerable interplay between these. The impact of perianal fistula(s) on patients with CD is intense and wide reaching, negatively affecting intimate, close and social relationships. Fistulas cause losses in life and work-related opportunities, and treatments can be difficult to tolerate. CONCLUSION Crohn's perianal fistulas exert a heavy negative physical and emotional impact on patients. These findings will inform development of a patient reported outcome measure to assess treatment effectiveness and quality of life for patients living with this challenging condition.
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Affiliation(s)
- Samuel O Adegbola
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Watford Road, Harrow, HA1 3UJ, Middlesex, UK.
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, Praed Street, London, W2 1NY, UK.
| | - Lesley Dibley
- Faculty of Education, Health and Human Sciences, University of Greenwich, London, UK
| | - Kapil Sahnan
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Watford Road, Harrow, HA1 3UJ, Middlesex, UK
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, Praed Street, London, W2 1NY, UK
| | - Tiffany Wade
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College, London, UK
| | | | | | | | | | - Nuha Yassin
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Watford Road, Harrow, HA1 3UJ, Middlesex, UK
| | - Robin K S Phillips
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Watford Road, Harrow, HA1 3UJ, Middlesex, UK
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, Praed Street, London, W2 1NY, UK
| | - Philip J Tozer
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Watford Road, Harrow, HA1 3UJ, Middlesex, UK
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, Praed Street, London, W2 1NY, UK
| | - Christine Norton
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College, London, UK
| | - Ailsa L Hart
- Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Watford Road, Harrow, HA1 3UJ, Middlesex, UK
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, Praed Street, London, W2 1NY, UK
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Lukin DJ. Predictors of Perianal Fistula Relapse in Crohn's Disease. Inflamm Bowel Dis 2020; 26:932-933. [PMID: 31504545 DOI: 10.1093/ibd/izz198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Indexed: 01/02/2023]
Affiliation(s)
- Dana J Lukin
- Jill Roberts Center for Inflammatory Bowel Disease, New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York, USA
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42
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Malian A, Rivière P, Bouchard D, Pigot F, Eléouet-Kaplan M, Favreau-Weltzer C, Poullenot F, Laharie D. Pedictors of Perianal Fistula Relapse in Crohn's Disease. Inflamm Bowel Dis 2020; 26:926-931. [PMID: 31504542 DOI: 10.1093/ibd/izz200] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Despite an optimal medico-surgical management of perineal Crohn's disease (PCD), fistula relapse still occurs in 30% of patients. Our aim was to determine predictors of fistula relapse in patients in remission after treatment of a PCD lesion. METHODS Consecutive patients treated for fistulizing PCD have been included in a retrospective study when they achieved fistula remission within 3 months after the surgery. Remission was defined as the absence of any draining fistula at clinical examination. Primary outcome was the occurrence of a fistula relapse, defined as a subsequent perianal draining fistula or an abscess confirmed clinically and/or by pelvic MRI. RESULTS One hundred and thirty-seven patients (57% female, median age: 35 years) corresponding to 157 abscess events, including 120 (76.4%) treated by anti-TNF after drainage, achieved fistula remission after surgery. During the follow-up period (median duration: 43 months [interquartile range 26 to 64]), 34 (22%) patients experienced a fistula relapse within a median time of 1.8 years. Survival without fistula was 96.7% at 1 year, 78.4% at 3 years, and 74.4% at 5 years. Fistula relapse rates were not different in patients receiving infliximab or adalimumab (P = 0.66). In patients treated by anti-TNF at inclusion, discontinuation of anti-TNF therapy (odds ratio 3.49, P = 0.04), colonic location (OR 6.25, P = 0.01), and stricturing phenotype (odds ratio 4.39, P = 0.01) were independently associated with fistula relapse in multivariate analysis. CONCLUSION In patients achieving fistula remission of PCD, relapse rates are low and are not different between infliximab and adalimumab. Discontinuation of anti-TNF therapy is associated with increased relapse rate.
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Affiliation(s)
- Audrey Malian
- Hépato-gastro-entérologie, Centre Hospitalier Universitaire, Bordeaux, France
| | - Pauline Rivière
- Hépato-gastro-entérologie, Centre Hospitalier Universitaire, Bordeaux, France
| | - Dominique Bouchard
- Proctologie, Maison de Santé Protestante Bordeaux-Bagatelle, Talence, France
| | - François Pigot
- Proctologie, Maison de Santé Protestante Bordeaux-Bagatelle, Talence, France
| | | | | | - Florian Poullenot
- Hépato-gastro-entérologie, Centre Hospitalier Universitaire, Bordeaux, France
| | - David Laharie
- Hépato-gastro-entérologie, Centre Hospitalier Universitaire, Bordeaux, France
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Spinelli A, Armuzzi A, Ciccocioppo R, Danese S, Gionchetti P, Luglio G, Orlando A, Rispo A, Rizzello F, Sofo L, Solina G, Poggioli G. Management of patients with complex perianal fistulas in Crohn's disease: Optimal patient flow in the Italian clinical reality. Dig Liver Dis 2020; 52:506-515. [PMID: 31901310 DOI: 10.1016/j.dld.2019.11.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 11/07/2019] [Accepted: 11/18/2019] [Indexed: 12/11/2022]
Abstract
Perianal fistulizing Crohn's disease (PFCD) is a common, disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Its successful treatment is still a struggle for both physicians and patients. Significant advances in the management of this condition have occurred in the last two decades holding promise for a better future. This culminated into the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical and endoscopic techniques. Despite this, PFCD management and treatment have not been standardized yet. Thus the gastroenterologist and surgeon have to be familiar with several approaches and/or techniques. The positioning of each therapeutic option will certainly evolve with new data, but for the time being it should be driven by patient's characteristics, physician's preference and/or experience, costs and availability in local practice. Additionally, patient's perception of benefits and risks of treatment may differ from those of physicians and recognition of this difference is a starting point for difficult clinical decision-making. In this paper, a multidisciplinary group of Italian IBD experts explore and discuss current medical and surgical therapeutic options, highlighting areas of unmet needs in PFCD, with particular focus on the optimal patient flow within the Italian clinical reality.
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Affiliation(s)
- Antonino Spinelli
- Division of Colon and Rectal Surgery, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy.
| | | | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, G.B. Rossi University Hospital, Verona, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy; IBD Center, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy
| | - Paolo Gionchetti
- Emilia-Romagna IBD Regional Referral Center, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Gaetano Luglio
- Surgery Unit, Department of Public Health, Federico II University Hospital, Naples, Italy
| | | | - Antonio Rispo
- Gastroenterology Unit, Federico II University Hospital, Naples, Italy
| | - Fernando Rizzello
- Emilia-Romagna IBD Regional Referral Center, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Luigi Sofo
- Abdominal SUrgery Unit, Department of Gastroenterology, Endocrine-metabolic and Nephrourological Science, A. Gemelli Hospital, Cattolica University, Rome, Italy
| | - Gaspare Solina
- Unit of General and Oncological Surgery, Department of Surgery, "Villa Sofia-Cervello" Hospital, Palermo, Italy
| | - Gilberto Poggioli
- Digestive Surgery Department, S. Orsola-Malpighi University Hospital, Bologna, Italy
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Sun XL, Chen SY, Tao SS, Qiao LC, Chen HJ, Yang BL. Optimized timing of using infliximab in perianal fistulizing Crohn's disease. World J Gastroenterol 2020; 26:1554-1563. [PMID: 32327905 PMCID: PMC7167413 DOI: 10.3748/wjg.v26.i14.1554] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 01/20/2020] [Accepted: 03/09/2020] [Indexed: 02/06/2023] Open
Abstract
Infliximab (IFX), as a drug of first-line therapy, can alter the natural progression of Crohn's disease (CD), promote mucosal healing and reduce complications, hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission. There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents. Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging. Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.
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Affiliation(s)
- Xue-Liang Sun
- First Clinical Medical College, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Department of Colorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215000, Jiangsu Province, China
| | - Shi-Yi Chen
- First Clinical Medical College, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Shan-Shan Tao
- First Clinical Medical College, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Li-Chao Qiao
- First Clinical Medical College, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Hong-Jin Chen
- First Clinical Medical College, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Bo-Lin Yang
- First Clinical Medical College, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
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Predictors of long-term outcomes of radiologically defined perianal fistulizing Crohn's disease treated with antitumor necrosis factor-alpha agents based on Parks' classification. Eur J Gastroenterol Hepatol 2020; 32:187-192. [PMID: 31851087 DOI: 10.1097/meg.0000000000001634] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Perianal fistulizing Crohn's disease (PFCD) leads to significant disability. Data assessing healing of complex PFCD based on pelvic MRI using Parks' classification remains sparse. We aimed to assess the frequency of closure of fistula tract on MRI in patients treated with antitumor necrosis factor alpha antagonists and identify predictors of poor response. MATERIALS AND METHODS We retrospectively identified patients registered in the Saudi Inflammatory Bowel Disease Information System registry, who were diagnosed as PFCD based on MRI and treated with infliximab or adalimumab. Fistulae were classified based on Parks' classification and response to treatment was determined as full, partial, or no response, after at least 12 months of treatment. RESULTS Out of 960 patients, 61 had complex PFCD that required treatment with an anti-TNF agent. The median age was 27 years (range: 14-69 years) and the median duration of disease was 6.2 ± 5.8 years. A full response to treatment was achieved in 27 (44.4%), whereas 10 patients (16.3%) had partial response and 24 (39.3%) had no response. On univariable analysis, a statistically significant association was observed between poor fistula response and low BMI, rectal involvement, fistulae classification, and the presence of an abscess. According to multivariable regression, only low BMI predicted poor fistulae outcome (odds ratio = 1.37, 95% confidence interval: 0.69-0.98). CONCLUSION Less than half of this cohort of patients with PFCD achieved complete radiological fistula healing with anti-TNF therapy. Low BMI appears to be the only predictor of poor outcome.
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Lee T, Yong E, Ding NS. Radiological outcomes in perianal fistulizing Crohn's disease: A systematic review and meta-analysis. JGH OPEN 2019; 4:340-344. [PMID: 32514434 PMCID: PMC7273731 DOI: 10.1002/jgh3.12295] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 12/01/2019] [Indexed: 12/17/2022]
Abstract
Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While rates of clinical response and remission are well characterized in literature, magnetic resonance imaging (MRI) outcomes remain less so. This is despite previous studies demonstrating the persistence of fistula tracts on MRI, in spite of clinical healing, suggesting radiological markers of improvement may be more accurate. The aims of this study were to systematically review the literature for all studies reporting on MRI outcomes following biological therapy and to compare rates of radiological healing to clinical remission. A search was performed according to the Preferred Reporting Items For Systematic Reviews and Meta‐Analysis (PRISMA) guidelines. Nine articles were included, with a total sample size of 259 patients. Of these 259 patients, 47% achieved clinical remission following induction therapy and 42% following a median of 52 weeks' maintenance therapy. Out of the 259 patients, 7% achieved radiological healing in the short term and 25% in the long term. The odds ratio of MRI versus clinical healing was 0.10 (95% confidence interval [CI], 0.02–0.39) and 0.43 (95% CI, 0.26–0.71), respectively, at those corresponding time points. MRI healing of perianal fistulizing Crohn's, while arguably a more accurate assessment of treatment response, is significantly less common than clinical remission. Heterogeneity exists in the definition of radiological and clinical response, leading to variation in reported rates. Further studies, directly comparing the long‐term outcomes of patients achieving clinical remission and MRI healing are required, to better inform the role of MRI follow up in clinical practice.
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Affiliation(s)
- Tanya Lee
- St Vincent's Clinical School University of Melbourne Melbourne Victoria Australia
| | - Eric Yong
- Department of Radiology St Vincent's Hospital Melbourne Victoria Australia
| | - Nik S Ding
- Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia
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Mak JWY, Tang W, Yip TCF, Ran ZH, Wei SC, Ahuja V, Kumar S, Leung WK, Hilmi I, Limsrivilai J, Aniwan S, Lam BCY, Chan KH, Ng KM, Leung CM, Li MKK, Lo FH, Sze ASF, Tsang SWC, Hui AJ, Hartono JL, Ng SC. Stopping anti-tumour necrosis factor therapy in patients with perianal Crohn's disease. Aliment Pharmacol Ther 2019; 50:1195-1203. [PMID: 31638274 DOI: 10.1111/apt.15547] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 09/16/2019] [Accepted: 09/29/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Little is known of the outcome of patients with perianal Crohn's disease after stopping anti-tumour necrosis factor (TNF) therapy. AIM To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti-TNF therapy. METHODS Consecutive perianal CD patients treated with anti-TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan-Meier method. RESULTS After a median follow-up of 89 months (interquartile range [IQR]: 65-173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti-TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti-TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01-1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti-TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58-2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti-TNF therapy after a median of 6 months. CONCLUSIONS More than half of the perianal CD patients developed relapse after stopping anti-TNF therapy. Most regained response after resuming anti-TNF. However, more than one-fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti-TNF is crucial in perianal CD.
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van Rijn KL, Lansdorp CA, Tielbeek JAW, Nio CY, Buskens CJ, D'Haens GRAM, Löwenberg M, Stoker J. Evaluation of the modified Van Assche index for assessing response to anti-TNF therapy with MRI in perianal fistulizing Crohn's disease. Clin Imaging 2019; 59:179-187. [PMID: 31821976 DOI: 10.1016/j.clinimag.2019.10.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 09/04/2019] [Accepted: 10/03/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Structured evaluation of magnetic resonance imaging (MRI) is important to guide clinical decisions of perianal fistulas in Crohn's disease (CD) patients. PURPOSE To evaluate the recently developed modified Van Assche index to assess clinical responses to anti-tumor necrosis factor (TNF) therapy in patients with perianal fistulizing CD. METHODS A search of medical records identified patients with fistulizing perianal CD who underwent baseline and follow-up MRI while receiving anti-TNF treatment. Patients were divided into clinical responders and non-responders based on physician's assessment. MRI-scans were scored using the original and modified Van Assche index and scores between baseline and follow-up were compared within clinical responders and non-responders. RESULTS Thirty cases were included (48% female, median age 27 years). Clinical responders (n = 16) had a median modified Van Assche score of 9.6 (IQR 5.8-12.7) at baseline and 5.8 (IQR 3.5-8.5) at follow-up (p = 0.008). In non-responders (n = 14), corresponding scores were 7.7 (IQR 5.8-13.5) and 8.2 (IQR 5.8-11.5) (p = 0.624). In clinical responders, 6/16 showed no drop in modified Van Assche score at follow-up. Scores obtained with the original Van Assche index dropped between baseline and follow-up in clinical responders (13.0 vs. 9.6, p = 0.011), whereas no decrease was observed in non-responders (11.5 vs. 11.5, p = 0.324). CONCLUSIONS While the modified Van Assche index overall decreases significantly in patients with perianal fistulas responding to anti-TNF treatment, one third of responders had unaltered scores at follow-up. Also, outcomes were comparable to the original Van Assche index. Further optimization of the modified Van Assche index is needed before application in larger studies.
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Affiliation(s)
- Kyra L van Rijn
- Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, Meibergdreef 9, Amsterdam, the Netherlands.
| | - Corine A Lansdorp
- Amsterdam UMC, University of Amsterdam, Department of Anesthesiology, Meibergdreef 9, Amsterdam, the Netherlands
| | - Jeroen A W Tielbeek
- Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, Meibergdreef 9, Amsterdam, the Netherlands
| | - C Yung Nio
- Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, Meibergdreef 9, Amsterdam, the Netherlands
| | - Christianne J Buskens
- Amsterdam UMC, University of Amsterdam, Department of Surgery, Meibergdreef 9, the Netherlands
| | - Geert R A M D'Haens
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Meibergdreef 9, Amsterdam, the Netherlands
| | - Mark Löwenberg
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Meibergdreef 9, Amsterdam, the Netherlands
| | - Jaap Stoker
- Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, Meibergdreef 9, Amsterdam, the Netherlands
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Adler J, Jary HK, Eder SJ, Dong S, Brandt E, Haraga JK, Dombkowski KJ. Identifying perianal fistula complications in pediatric patients with Crohn's disease using administrative claims. PLoS One 2019; 14:e0219893. [PMID: 31412045 PMCID: PMC6693740 DOI: 10.1371/journal.pone.0219893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 07/04/2019] [Indexed: 12/18/2022] Open
Abstract
Background Although perianal fistulas occur commonly in pediatric Crohn’s disease (CD), evaluations of health services have been limited since no validated claims-based methods exist for identifying cases. Objective To develop and validate accurate case definitions for perianal fistulas among pediatric patients with CD from administrative claims. Methods Retrospective cohort study in which we developed and tested candidate case definitions for perianal fistula. Patients (age 5–21 years between 2005–2012) with CD enrolled in Michigan Medicaid with healthcare at University of Michigan were identified via claims. Medical records were obtained from all identified patients, whose entire records were abstracted. Medical record evidence for perianal fistula was considered the “gold standard” against which candidate case definitions were compared. The reference case definition of perianal fistula (ICD9 565.1) and candidate case definitions were evaluated. Results Of 843 patients identified via claims, 274 (33%) met CD criteria for inclusion. The true perianal fistula rate among CD patients was 18% (n = 49). The top-performing candidate case definition identified 15% (n = 42), had sensitivity of 77.6%, specificity of 98.2%, positive predictive value (PPV) 90.5%, negative predictive value (NPV) 95.3%, and area under receiver operator characteristic curve (ROC) of 0.88. In contrast, the reference case definition identified 9% (n = 26), sensitivity 51.0%, specificity 99.6%, PPV 96.2%, NPV 90.3%, and had an area under ROC of 0.75. Conclusions We demonstrated that it is feasible to use administrative claims data to accurately identify pediatric patients with perianal fistula complications. Claims-based case definitions were found to be highly accurate through medical record review, providing a high degree of confidence for future studies where chart review is not feasible. These claims-based methods can be applied to claims data in other settings for the evaluation of health services utilization as well as to assess the comparative effectiveness of prevention and treatment strategies.
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Affiliation(s)
- Jeremy Adler
- Department of Pediatrics and Communicable Diseases, Division of Pediatric Gastroenterology, University of Michigan, Ann Arbor, Michigan, United States of America
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor Michigan, United States of America
- * E-mail:
| | - Hannah K. Jary
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor Michigan, United States of America
| | - Sally J. Eder
- Department of Pediatrics and Communicable Diseases, Division of Pediatric Gastroenterology, University of Michigan, Ann Arbor, Michigan, United States of America
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor Michigan, United States of America
| | - Shiming Dong
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor Michigan, United States of America
| | - Emily Brandt
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor Michigan, United States of America
| | - Jessica K. Haraga
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor Michigan, United States of America
| | - Kevin J. Dombkowski
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor Michigan, United States of America
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