Jjae 089

Manuscript Doi: 10.
1093/ecco-jcc/jjae089
ECCO Guidelines on Therapeutics in Crohn's Disease:
Surgical Treatment
Michel Adamina1,2, Silvia Minozzi, Janindra Warusavitarne, Christianne Buskens, Maria
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Chaparro, Bram Verstockt, Uri Kopylov, Manasi Agrawal, Mariangela Allocca, Raja Atreya,
Robert Battat, Dominik Bettenworth, Gabriele Bislenghi, Steven Ross Brown, Johan Burisch,
María José Casanova, Wladyslawa Czuber-Dochan, Joline de Groof, Alaa El-Hussuna,
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Pierre Ellul, Catarina Fidalgo, Gionata Fiorino, Javier Gisbert, João Guedelha Sabino, Jurij
Hanzel, Stefan Holubar, Marietta Iacucci, Nusrat Iqbal, Christina Kapizioni, Konstantinos
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Karmiris, Taku Kobayashi, Paulo Gustavo Kotze, Gaetano Luglio, Christian Maaser, Gordon
Moran, Nurulamin Noor, Konstantinos Papamichail, Georgios Peros, Catherine Reenaers,
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Giuseppe Sica, Rotem Sigall-Boneh, Stephan R. Vavricka, Henit Yanai, Tim Raine, Hannah
Gordon, Pär Myrelid
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Michel Adamina 1. Department of Surgery, Cantonal Hospital of Fribourg & Faculty of Science and
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Medicine, University of Fribourg, Fribourg, Switzerland

2. Department of Visceral and Thoracic Surgery, Kantonsspital Winterthur,
Winterthur, Switzerland
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Silvia Minozzi Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
Janindra St Mark’s Hospital London; United Kingdom
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Warusavitarne
Christianne Department of Surgery, Amsterdam UMC, Location VUMC, Amsterdam, The
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Johanna Buskens Netherlands

Maria Chaparro Gastroenterology Department. Hospital Universitario de La Princesa, Instituto de
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Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid

(UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y
Digestivas (CIBEREHD), Madrid; Spain
Bram Verstockt Department Gastroenterology & Hepatology, University Hospitals Leuven, KU
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Leuven and Dpt. Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
Uri Kopylov Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
Henit Yanai IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva;
Faculty of Medicine, Tel Aviv University, Tel Aviv; Israel
Stephan R. Department of Gastroenterology and Hepatology, University Hospital Zürich,
Vavricka Zürich, Switzerland
Rotem Sigall- Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson Medical Center,
Boneh Holon, Israel.
Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology
Endocrinology and Metabolism, University of Amsterdam, Amsterdam, the
Netherlands
Giuseppe S. Sica Department of Surgery, Università Tor Vergata, Roma, Italy
© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and
Colitis Organisation. All rights reserved. For permissions, please email:
[email protected]
Manuscript Doi: 10.1093/ecco-jcc/jjae089
Catherine Gastroenterology Department, Chu Liege, Liege, Belgium
Reenaers
Georgios Peros Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
Konstantinos Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth
Papamichael Israel Deaconess Medical Center, Harvard Medical School, Boston,
Massachusetts
Nurulamin Noor Department of Medicine, University of Cambridge, Cambridge, United Kingdom
Gordon William 1. National Institute of Health Research Nottingham Biomedical Research

Moran Centre, University of Nottingham and Nottingham University Hospitals,
Nottingham
2. Translational Medical Sciences, School of Medicine, Faculty of Medicine
and Health Sciences, University of Nottingham, Nottingham. NG7 2UH. United
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Kingdom
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Christian Maaser Outpatients Department of Gastroenterology, University Teaching Hospital
Lueneburg, Germany
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Gaetano Luglio Department of Public Health, University of Naples Federico II, Naples, Italy
Paulo Gustavo Health Sciences Postgraduate Program, Pontificia Universidade Católica do
Kotze Paraná (PUCPR), Curitiba, Brazil
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Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato
Institute Hospital, Tokyo, Japan
Konstantinos Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Greece
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Karmiris
Christina Department of Gastroenterology, Attikon University Hospital, Athens, Greece
Kapizioni
Nusrat Iqbal Department of Surgery, Worcestershire Acute Hospitals NHS Trust, Worcester,
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UK.
Marietta Iacucci APC Microbiome Ireland, College of Medicine and Health, University College of
Cork, Cork, Ireland
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Stefan Holubar Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, Ohio, USA
Jurij Hanzel Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana;
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Chair of Internal Medicine, Faculty of Medicine, University of Ljubljana,

Ljubljana, Slovenia
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João Guedelha Department of Gastroenterology and Hepatology, University Hospitals Leuven,

Sabino Leuven, Belgium
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Javier P. Gisbert Gastroenterology Department. Hospital Universitario de La Princesa, Instituto de

Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid
Digestivas (CIBEREHD), Madrid, Spain
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Gionata Fiorino IBD Unit, San Camillo-Forlanini Hospital, Rome, Italy

Catarina Fidalgo Division of Gastroenterology, Hospital Beatriz Ângelo, Loures
Division of Gastroenterology, Hospital da Luz, Lisboa
Portugal
Pierre Ellul Division of Gastroenterology, Mater Dei Hospital, Malta
Alaa El-Hussuna OpenSourceResearch Organization (OSRC.Network), Aalborg, Denmark
Joline de Groof Colorectal Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
Wladyslawa Florence Nightingale Faculty of Nursing- Midwifery and Palliative Care, King’s
Czuber-Dochan College London, London, United Kingdom
María José Gastroenterology Department. Hospital Universitario de La Princesa, Instituto de
Casanova Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid
Digestivas (CIBEREHD), Madrid. Spain
Johan Burisch Gastrounit, Medical Division, Copenhagen University Hospital - Amager and
Hvidovre, Hvidovre; Copenhagen Center for Inflammatory Bowel Disease in
Children, Adolescents and Adults, Copenhagen University Hospital - Amager and
Hvidovre, Hvidovre, Denmark
Steven Ross Department of Surgery, Sheffield Teaching Hospitals, Sheffield UK
Brown
Gabriele Department of Abdominal Surgery, University Hospitals Leuven, Belgium

Bislenghi
Dominik CED Schwerpunktpraxis, Münster and Medical Faculty of the University of
Bettenworth Münster, Münster, NRW, Germany
Robert Battat Division of Gastroenterology, Centre Hospitalier de l’Université de Montréal,
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Montreal, Canada
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Raja Atreya First Department of Medicine, Friedrich-Alexander-University Erlangen-
Nürnberg, Erlangen, Germany.
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Mariangela IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele,
Allocca Gastroenterology and Endoscopy, Milan, Italy
Manasi Agrawal 1. The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of
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Medicine at Mount Sinai, New York, New York, USA
2. Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT),
Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
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Tim Raine Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge University
Hospitals NHS Foundation Trust, Cambridge, United Kingdom
Hannah Gordon Translational Gastroenterology and Liver Unit, University of Oxford, Oxford, UK
Pär Myrelid Department of Surgery and Department of Biomedical and Clinical Sciences,
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Linköping University, Linköping, Sweden

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Corresponding author: Prof. Dr. Michel Adamina, MD, PD, MSc, EMBA HSG, FEBS,
FASCRS, Chairman, Department of Surgery, Cantonal Hospital Fribourg, Chemin des
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Pensionnats 2/6, 1752 Villars-sur-Glâne, Switzerland. Tel. +41 26 306 25 10; Email
[email protected]
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Abstract
This article is the second in a series of two publications on the European Crohn’s and Colitis
Organisation [ECCO] evidence-based consensus on the management of Crohn’s disease.
The first article covers medical management; the present article addresses surgical
management, including preoperative aspects and drug management before surgery. It also
provides technical advice for a variety of common clinical situations. Both articles together
represent the evidence-based recommendations of the ECCO for Crohn’s disease and an

update of prior ECCO guidelines.
Keywords: Crohn’s disease; Surgery; Inflammatory bowel disease (IBD)
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1. Introduction
The incidence and prevalence of Crohn’s disease [CD] is on the rise globally, with increases
in incidence ranging from 4–15% yearly over the last three decades.1 CD is a lifelong disease
and optimal management is multidisciplinary and interprofessional and has become
increasingly complex. Surgery is a major therapeutic avenue in this context. Indeed, half of

patients with CD undergo one or more operations during their lifetime. Patients with CD often
suffer from malnutrition, psychological comorbidities, and may have to accept and live with a
stoma.2-5 Many different medications and combinations thereof are reshaping clinical practice,
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while refined surgical techniques, tailored approaches, and a wider acceptance of a surgical
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alternative benefit patients. Hence, the best possible outcomes are currently achieved within
dedicated expert centres providing personalized medicine.6-10 The European Crohn’s and
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Colitis Organisation [ECCO] provides an interdisciplinary framework with these evidence-
based guidelines to inform and guide practice and clinicians caring for patients with CD. The
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present guidelines focus on surgery for CD, including pre- and perioperative aspects, and
provides technical advice for a variety of common clinical presentations. Further, ECCO
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guidelines offer guidance on most aspects of interdisciplinary and interprofessional care for
CD in separate publications.11-16
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2. Methods
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A detailed description of the methodology used is presented in the supplementary materials.

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This article is the second in a series of two publications on the ECCO evidence-based
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consensus on the management of CD. The first article covered medical management; 17 the
present article is focused on surgical management while covering both medical and surgical
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management of perianal CD. These two articles together represent the evidence-based
recommendations of the ECCO for CD and update prior guidelines published in 2020.18,19 The
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present guidelines follow the GRADE methodology in terms of framing clinically relevant
questions to draw evidence-based statements and recommendations. However, due to the
peculiarities of the surgical literature, appraisal of the systematically researched literature was
conducted according to the Oxford Centre for Evidence-Based Medicine, which grades from
evidence level [EL]1: systematic review of randomized controlled trials to EL5: expert
opinion.20 This allowed us to formulate statements and practice recommendations that can
effectively inform and guide clinical management.
3. Perianal Crohn’s disease
3.1. Medical approaches

Statement 3.1 ECCO CD Treatment GL [2024]
We do not recommend use of antibiotics as monotherapy for treatment of complex
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perianal fistulae in patients with CD [EL4]
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Although antibiotics are widely used in the treatment of perianal CD, most available studies
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are uncontrolled.21 To our knowledge, only one randomized controlled trial [RCT] compared
placebo with antibiotics in perianal fistulae [supplementary table 1]. Remission at week 10
was observed in 1/8 [12.5%] versus 3/17 [17.6%] patients treated with placebo or antibiotics,
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respectively (relative risk [RR]: 1.41; 95% confidence interval [CI]: 0.17–11.54]. Complete
healing was observed in 3/10 [30%] patients treated with ciprofloxacin and 0/8 patients
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treated with metronidazole.22 Uncontrolled data and data from studies on combination
therapy with anti-TNF suggest that ciprofloxacin can improve the efficacy of anti-TNF in the
short term with good safety but with no impact on longer-term healing rates.23,24 Importantly,
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despite the lack of evidence to support their role as monotherapy in closing perianal fistulae,
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antibiotics are indicated and recommended to treat and control perianal sepsis.
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We suggest against using thiopurines as monotherapy [azathioprine, mercaptopurine]

for treatment of complex perianal fistulae in patients with CD [EL3]
The effect of azathioprine [AZA] on fistula healing in perianal CD has been numerically
reported in RCTs in 18 patients only.25-28 A meta-analysis on this limited group of patients
demonstrated that AZA is not superior to placebo for fistula healing [RR: 2.00; 95% CI: 0.67–
5.93].29 Another study reported complete fistula closure in 9/29 [31%] fistulae during
mercaptopurine therapy, in contrast to 1/17 [6%] with placebo-treated fistulae30
[supplementary table 2]. Nevertheless, these data could not be incorporated in the pooled
analysis, as they were reported as number of fistulae closing rather than number of patients
who had complete fistulae closing. With the availability of effective anti-TNF agents, it seems
inappropriate to recommend any further randomized placebo-controlled trial studying the
efficacy of AZA in complex perianal fistulae.

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We recommend infliximab for the induction and maintenance of remission in complex
perianal fistulae in CD [EL2]
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Infliximab was the first agent shown to be effective in a RCT for inducing closure of perianal
fistulae and for maintaining this response over 1 year. Complete response [defined as the
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absence of any draining fistulae at two consecutive visits at least 4 weeks apart] was
observed in 4/31 [12.9%] placebo-treated patients versus 29/63 [46%] infliximab-treated
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patients [RR: 3.57; 95% CI: 1.38–9.25].31 Subsequently, the ACCENT II trial evaluated the
efficacy of infliximab [5 mg/kg every 8 weeks] in a maintenance trial in 195 patients who had
a response [defined as a reduction of 50% of draining fistulae in two visits at least 4 weeks
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apart] at week 14 after open-label induction treatment with infliximab. A complete response
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was maintained until week 54 in 19/99 [19.2%] placebo-treated patients versus 33/96
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[34.4%] infliximab-treated patients [RR: 1.79; 95% CI: 1.10– 2.92].32 A recent meta-analysis
of the existing data revealed that infliximab was effective in inducing [RR: 3.57; 95%
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CI:1.38–9.25] and maintaining clinical fistula healing [RR: 1.79; 95% CI:1.10–2.92] 33 with no
significant risk of serious AEs as compared with placebo [RR: 1.31; 95% CI: 0.11–15.25,
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supplementary figure 1]. A combined evaluation of both RCTs for safety revealed a risk of
serious AEs of 18.9% [33/175 patients] in the placebo groups versus 11.9% [24/201
patients] in the infliximab groups. Overall, the most recent meta-analysis (2023) provided low
certainty on clinical outcomes. Some retrospective data suggest that fistula healing is more
likely in patients with higher infliximab trough levels, suggesting the need for personalized
dosing in this setting.34-38
We suggest use of adalimumab for induction and maintenance of remission in

complex perianal fistulae in CD [EL3]

Fistula healing in the subgroup of patients with enterocutaneous or perianal fistulae [or both]
at baseline [n = 117] was a secondary endpoint of the CHARM double-blind, placebo-
controlled, randomized trial.39 A subsequent post-hoc analysis that focused specifically on
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the efficacy of adalimumab over time in this subgroup confirmed the superiority of
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adalimumab over placebo [RR: 2.57; 95% CI: 1.13–5.84] for fistula healing after 56 weeks39
[supplementary table 3]. Data from CHARM combined with data from the open-label
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extension study ADHERE revealed that there was no significant increase in serious AEs for
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patients treated with adalimumab [RR: 1.21; 95% CI: 0.43–3.38].40-43 Data were insufficient
to ascertain maintenance of fistula healing beyond 56 weeks, resolution of perianal sepsis,
stoma-free survival, and quality of life. In a retrospective multicentre analysis evaluating 46
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patients [83% with complex fistula] naïve to anti-TNF therapy, 72% of patients responded to
adalimumab [54% remission, 18% partial response] at 6 months and 49% of patients
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maintained response at 12 months [41% remission, 8% partial response].44 Additional data

suggested that adalimumab may have a role in patients who failed infliximab because of
immunogenicity [either primary non-responders or secondary loss-of-response]. The open-
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label CHOICE trial indeed demonstrated that complete fistula healing [mainly perianal fistula]
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could be achieved in 39% [34/88] of patients who initiated adalimumab after infliximab
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failure.42 This finding has also been reported in a limited case series.41 Some retrospective
data suggest that fistula healing is more likely in patients with higher adalimumab trough
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levels, suggesting the need for personalized dosing in this setting.35,37,40,45

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There is insufficient evidence to recommend use of certolizumab pegol as a treatment

for complex perianal fistulae in patients with CD [EL4]
Certolizumab pegol [CZP], a pegylated humanized Fab' fragment that targets TNF-α, was
evaluated for treatment of CD in two RCTs [PRECISE 1 and PRECISE 2]. The PRECISE 1
study included 662 patients with moderate-to-severe CD who were randomly assigned to
receive either CZP 400 mg or placebo subcutaneously at weeks 0, 2, and 4, followed by
administration every 4 weeks up to week 26.46 Fistula closure was a secondary endpoint;
30% [14/46] of patients in the CZP group achieved closure versus 31% [19/61] in the

placebo group. According to this study, CZP did not show a significant benefit for fistula
closure.
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The PRECISE 2 trial included 668 adults with moderate-to-severe CD47 and used the same
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induction therapy as in PRECISE 1. Patients with clinical response [reduction of ≥100 from
baseline score on the Crohn’s disease activity index] were randomly assigned to receive
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CZP 400 mg or placebo every 4 weeks through week 26. Among patients responding to
induction therapy with CZP, 28 of those randomized to CZP and 30 of those randomized to
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placebo had draining fistulae at baseline. The primary endpoint of the fistula subanalysis
was fistula closure, defined as ≥50% closure at two consecutive post-baseline visits ≥3
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weeks apart. At week 26, 54% [15/28] of CZP-treated patients achieved fistula closure [per
protocol] compared with 43% [13/30] of placebo-treated patients; the difference was not
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statistically significant [p = 0.069]. At week 26, 36% of patients in the CZP group achieved
complete fistula closure compared with 17% in the placebo group [p = 0.038]. Among
patients who achieved the predefined criteria for fistula closure, there was a higher
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numerical proportion of patients who received continuous treatment with CZP compared with
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those who initially underwent induction therapy followed by placebo. However, these
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differences were not statistically significant for the small sample size analysed. Patients
randomized to CZP in the maintenance phase maintained a 50% fistula closure rate at week
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26 (11/15 [73%] patients vs 39% [5/15] patients; p = 0.069) and achieved 100% closure at
week 26 (10/15 [67%] patients vs 4/13 [31%] patients; p = 0.064). The results from these
post-hoc analyses suggest a possible effect of CZP in complex perianal fistulae in CD.
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However, possibly due to limited sample size, the benefit of CZP over placebo was not
demonstrated.
There is insufficient evidence to recommend use of vedolizumab for the treatment of


Vedolizumab [VDZ], a gut-selective α4β7 integrin antibody, was assessed for the treatment
of complex perianal fistulae in an exploratory analysis of data from the GEMINI 2 study. 48
GEMINI 2 was a phase 3, randomized, double-blind, placebo-controlled trial that consisted
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of separate induction and maintenance phases. Following a 6-week induction period with
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VDZ, responders were randomly assigned to receive either placebo [VDZ/placebo group] or
VDZ [VDZ/VDZ group] and entered a maintenance phase. Fistula closure was defined as the
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absence of clinically draining fistulae at weeks 14 and 52. A total of 57 patients with draining
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fistulae at the start of the maintenance period were included in the analysis; half of them
previously failed anti-TNF therapy. By week 14, 28% [11/39] of patients in the VDZ/VDZ
group and 11% [2/18] of patients in the VDZ/placebo group achieved fistula closure.
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However, in a meta-analysis, maintenance with VDZ did not reach statistical significance
[RR: 2.54; 95% CI: 0.63–10.29; p = 0.19].49 At week 52, 31% in the VDZ/VDZ group and
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11% in VDZ/placebo group had fistula closure. Despite the numerically greater proportion of
fistula healing observed in patients treated with VDZ, no statistically significant differences
were observed. This post hoc analysis has several limitations, including a small sample size
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and inadequate statistical power. It is also biased by the induction phase with VDZ and lacks
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a design specifically evaluating VDZ for fistula closure.

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A small clinical trial compared the efficacy of standard VDZ dosing versus standard dosing
plus an additional dose at week 10 in patients with ≥1 draining perianal fistula at baseline. 50
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Fistula closure was observed at week 30 in 12 [42.9%] patients (7 patients in the standard
and 5 patients in the additional VDZ dose group).
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In summary, the available evidence is of low quality and insufficient to recommend VDZ for
complex perianal fistulae in patients with CD. However, VDZ could be considered in patients
refractory or intolerant to anti-TNF therapy. Further studies with appropriate design are
warranted to determine the benefit of VDZ in the treatment of complex perianal fistulae.
There is insufficient evidence to recommend use of ustekinumab as a treatment for


The sole study comparing ustekinumab to placebo in treating complex perianal fistulae was
a post hoc pooled analysis of data from the phase 2 CERTIFI and from the phase 3 UNITI-1
and UNITI-2 trials. This analysis provided information on the induction of fistula response
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and remission rates.51 A total of 150 patients were treated with ustekinumab and 71 were
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treated with placebo. Due to the limited sample size, data from the final induction visit at
week 8 were aggregated across the three studies for evaluation. The analysis revealed a
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higher proportion of fistula closure after 8 weeks of treatment in the ustekinumab group
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[24.7%] compared with the placebo group [14.1%], although the observed difference did not
reach statistical significance [p = 0.073]. This finding was confirmed in a meta-analysis [RR:
1.77; 95% CI: 0.93–3.37].49
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In the maintenance phase, fistula response to treatment was assessed at week 22 and 44.
However, all patients included in the maintenance phase were either responders or non-
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responders to induction with ustekinumab who were re-randomized to receive ustekinumab

or placebo, which may bias the results. Among patients in the maintenance phase, fistula
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response at week 22 occurred in 9/19 [47%] patients in the ustekinumab group and in 6/20
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[30%] patients in the placebo group of the CERTIFI study and in 12/15 [80%] and 5/11
[45.5%] patients, respectively, at week 44 in the IM-UNITI study. Despite the numerically
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higher proportion of fistula healing in patients treated with ustekinumab, no significant

differences were found. Moreover, being a post hoc analysis, fistula response or remission
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was a secondary outcome, making it an exploratory study with insufficient statistical power
and a small sample size. In a recent meta-analysis that included 25 studies [most of which
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were observational studies and 20% of them being abstracts], 24.7% of patients achieved
clinical remission of complex perianal fistulae at weeks 8–12 and 41.9% at 12 months.52
Overall, there is insufficient evidence to recommend ustekinumab for treatment of complex
perianal fistulae in patients with CD. However, ustekinumab could be considered in patients
with perianal fistulae who are refractory or intolerant to anti-TNF agents. Further studies with
appropriate design are warranted to determine the benefit of ustekinumab in the treatment of
complex perianal fistulae.
There is insufficient evidence to recommend use of upadacitinib for the treatment of

complex perianal fistulae in CD [EL4].

Upadacitinib [UPA] is currently the only JAK inhibitor approved for CD. Patients with
moderate-to-severe CD were randomized to UPA 45 mg once daily or placebo for 12 weeks
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in two phase 3 induction trials. Patients who achieved clinical response after 12 weeks of
UPA therapy were randomly assigned to receive UPA 30 mg or 15 mg or placebo once daily
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for 52 weeks. Among 1021 enrolled patients, 143 patients had fistulae at baseline [124
patients had perianal fistulae, 19 had enterocutaneous fistulae]. Post hoc analyses
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published as an abstract reported that in patients with draining fistulae at baseline, the
proportion of patients with ≥50% reduction in draining fistulae at week 12 was significantly
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higher with UPA 45 mg compared with placebo (22/44 [50%] patients vs 3/22 [13.6%]
patients; p = 0.004).
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Furthermore, complete resolution of draining fistulae at week 12 was also significantly higher
with UPA 45 mg than with placebo (21/44 [47.7%] patients vs 2/22 [9.1%] patients; p =
0.002). Numerically, a similar resolution pattern was seen in patients treated with either UPA
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30 mg or 15 mg (1/11 [9.1%] and 3/17 [17.6%] patients, respectively vs 0/8 [0%] placebo-
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treated patients). Closure of the external fistula opening at week 52 was higher with either
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UPA 30 mg or 15 mg (4/19 [21.1%] and 6/35 [17.1%] patients, respectively vs 0/25 [0%]
placebo-treated patients).53 Nevertheless, this post hoc analysis has several limitations,
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including small sample size and inadequate statistical power.
In summary, the available evidence is of low quality and insufficient to recommend UPA as
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treatment for complex perianal fistulae in patients with CD. Further studies with appropriate
design are warranted to determine the benefit of UPA in the treatment of complex perianal
fistulae.
There is lack of evidence to recommend use of risankizumab for the treatment of


3.2. Surgical techniques
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We recommend fistulotomy in carefully selected CD patients with a simple fistula in
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the absence of proctitis [EL4]
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Studies on fistulotomy in CD are largely retrospective single-centre studies with specific
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eligibility criteria, including Parks classification superficial, intersphincteric, or low
transsphincteric fistula,54-60 absence of proctitis,57,58 quiescent abdominal disease,61 and a
low number of daily bowel motions.57 Few studies have compared the outcomes of
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fistulotomy in these select patients with alternative surgical procedures, which were mostly
performed in patients with more complex or high anal fistulae. Due to this selection bias,
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these studies demonstrated improved healing and reduced recurrence rates in patients
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undergoing fistulotomy when compared with sphincter-preserving procedures, seton

removal, and mesenchymal stem cells [MSC].55,58,60. In the largest studies, recurrence rates
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of 3–13% up to 1 year post-fistulotomy55,57,58,60 were reported. However, few studies provide

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robust data on continence and wound healing. Other reports present data from
heterogenous populations, including non-CD fistulae54,59 or those undergoing multiple
procedures prior to fistulotomy,62 highlighting the difficulty in drawing recommendations from
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such data. Therefore, fistulotomy can only be recommended in simple, superficial, or low
anal fistulae with absence of proctitis and stable intestinal disease.
We suggest advancement flap as a treatment option for selected patients with CD and
complex perianal fistulae in the absence of proctitis [EL4]
Fistula closure can be achieved by raising a flap of mucosal tissue within the anus and lower
part of the rectum. The advancement [AF] flap is then used to cover the internal opening of
the fistula. CD patients with a single internal fistula opening and without proctitis or an anal
stenosis are eligible. A systematic review identified 11 retrospective studies that reported
data from 135 patients with CD perianal fistulae treated with an AF.63 The pooled success
rate was 66%. However, results were heterogeneous, probably due to varying definitions of

success and length of follow-up. In a more recent meta-analysis, Stellingwerf et al. observed
a weighted overall success rate of 61% in CD patients.64 Results were not significantly
different when compared with the success rate of ligation of the intersphincteric fistula tract
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[LIFT] procedure.
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Additional prospective and retrospective series not included in the meta-analyses showed
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comparable clinical healing rates with AF, ranging from 47–90%65-68 and recurrence rates
around 15–20%. Two studies showed a higher clinical healing rate when AF was performed
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in patients treated with anti-TNF/immunomodulators [75.0% vs 37.5%] and after seton
drainage.68 One study also showed a 100% success rate in diverted patients.66
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The disadvantage of AF is risk of impaired continence. The systematic review showed an
acceptable postoperative incontinence rate, which was higher in AF when compared with the
LIFT procedure [7.8% vs 1.6%].64 However, most prospective series revealed a
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postoperative higher incontinence rate of up to 20% following AF. Conversely, one

retrospective study reported a postoperative improvement in faecal continence.68
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pt

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We recommend ligation of the intersphincteric fistula tract as a treatment option for

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selected patients with CD and complex perianal fistulae [EL3]
LIFT aims to achieve fistula closure by ligation of the fistula tract in the intersphincteric
plane, close to the internal opening. A theoretical advantage of LIFT over AF in CD patients
is that it does not involve surgery of the [diseased] mucosa. Patients with a single, non-
branching fistula and a well epithelialized tract are preferably eligible.
Two systematic reviews and meta-analyses, both including approximately 1300 patients,
demonstrated a high clinical success rate of 77% and 69% [range 47–95%], respectively,
after a median follow-up of over 1 year.64,69 However, there was only a minority of patients
with CD in these studies, and these patients had a lower success rate of 53%. Included
studies were heterogeneous, with a wide range of outcomes and follow-up times, which
makes it difficult to draw firm conclusions. The described recurrence rates were low [1.6%]
and compared favourably to AF [7.8%].

Two retrospective and one prospective study published after the aforementioned meta-
analyses reported results on an additional 95 patients with CD.68,70,71 Clinical closure rates
were comparable with the results previously published. However, data on recurrence were
t
only reported in one series, with a rate of 21%.70 Overall, this suggests a possible
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underreporting in the systematic reviews and meta-analyses. Another retrospective study
demonstrated that in patients with a [predominantly] fibrotic tract after LIFT at MRI, no
cr
reinterventions or recurrences were seen during long-term follow-up, which also emphasizes
the requirement of radiological healing to consider a patient healed.68
us
The only prospective series included 46 patients with a mean follow-up of 33 months and
demonstrated fistula healing in 65% of patients.71 Smoking at time of surgery was
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significantly associated with failure (hazard ratio [HR] 3.2), and a trend was seen towards
increased failure in patients with active proctitis [HR 2.0]. No other factors [use of biologics,
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prior seton drainage, type of fistula, previous repair attempts] appeared to influence LIFT
healing.
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Postoperative complications after LIFT were seen in up to 14% of patients and were
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predominantly wound dehiscence. Incontinence rates appeared to be lower when compared

pt
with AF. However, continence should be interpreted with caution as there is a risk of under-
reporting in the literature. The only retrospective series specifically examining postoperative
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incontinence in 37 patients demonstrated increased incontinence in 16% of patients after

LIFT, whereas 53% of patients operated with LIFT and 43% with AF reported a
postoperative improvement in faecal continence.68
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We recommend against the use of fibrin glue in the treatment of patients with
complex perianal CD fistulae [EL4]
Fibrin glue for treatment of perianal CD fistulae was assessed in an open-label RCT with 71
patients randomized to instillation of fibrin glue into the fistula tract or no further treatment
after seton removal.72 This RCT demonstrated a significant difference in overall clinical
remission rate [38% for fibrin glue and 16% in the observation group; p = 0.04]. However,
the length of follow-up in this RCT was only 8 weeks and was insufficient for a definitive
judgement on the true success rate. The only retrospective series with adequate follow-up

time [5 years] suggested an acceptable healing rate of 45% at 1 year,73 but the single
predictor for complete clinical remission was combination with medical therapy. This series
also demonstrated a worrisome cumulative incidence of iterative anal surgery of 54% within
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5 years, suggesting a high recurrence rate after fibrin glue. Despite the limited efficacy of
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fibrin glue in daily clinical practice, a uniform characteristic of all studies is the relatively good
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safety profile of this technique with no reported injury to the sphincter muscles.
us
an
We recommend against anal fistula plug in the treatment of patients with complex
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perianal CD fistulae (EL4)

e d
Use of a collagen anal fistula plug [AFP] in patients with perianal CD fistulae was assessed
in a single RCT including 106 patients, which compared AFP after seton removal with seton
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removal only.74 The fistula closure rate after 12 weeks in the AFP group was 33.3% in
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patients with complex fistulae and 30.7% in patients with simple fistulae as compared with
15.4% and 25.6% with seton removal alone, respectively. These differences were not
statistically significant. In addition, there was a trend towards more adverse events [AE] in
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the AFP group [17% vs 8%; p = 0.07], although cumulative AE rates at 12 months follow-up
were similar.
A systematic review of 12 observational studies including 84 patients with CD demonstrated

an overall AFP success rate of 58%, with 14% recurrence after median follow-up of 9 [3–24]
months.75 However, there was no uniform definition for fistula closure or follow-up regimen.
The quality of evidence for this systematic review was low due to risk of bias and
imprecision. Use of an AFP in patients with CD appears to be relatively safe and may not
affect continence [limited data on continence reported].76 However, in studies using AFP for
cryptoglandular fistulae, the abscess formation/sepsis rate ranged from 4–29% and the plug
extrusion rate from 4–41%.77

There is insufficient evidence to recommend use of video-assisted anal fistula
treatment, fistula-tract laser closure, or over-the-scope clip for achieving healing in
t
ip
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The role of video-assisted anal fistula treatment [VAAFT] in the treatment of anal fistulae in
CD has been investigated only in small cohort studies. A first retrospective study including a
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mixed population of 84 patients with cryptoglandular and CD fistulae [n = 11] with a limited
median follow-up of 8 months revealed a 27% healing rate in patients with CD.78 Data on
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postoperative complications and risk of postoperative incontinence were lacking. A second
retrospective study reported an overall healing rate of 82% at 9 months follow-up.79
However, these results are difficult to interpret due to the very limited sample size of 11
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patients and by the fact that internal opening closure was achieved by fashioning a rectal
advancement mucosal flap. Furthermore, in about 40% of patients, faecal diversion [FD] was
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present at time of surgery. No patients experienced postoperative morbidity or postoperative

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faecal incontinence. VAAFT was further evaluated in a retrospective analysis of

prospectively collected data of 25 patients with anal fistulae refractory to multiple previous
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surgeries and adequate medical treatment with biologics.80 Twenty-one of 25 patients [84%]
had a statistically significant improvement in a quality-of-life questionnaire before and 6
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weeks after surgery, in particular in both pain and discharge scores. Eighty-one percent
agreed that the procedure was the right decision and no patient regretted undergoing the
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procedure. Reoperation was necessary in one patient [4%].
Fistula-tract laser closure [FiLaC] is a relatively new sphincter-preserving technique initially

reported in 2011. A systematic review published in 2022 identified six retrospective studies
investigating FiLAC as a treatment option for perianal CD on a total of 50 patients.81 There
was heterogeneity in length of follow-up, fistula characteristics, and outcomes reported. The
techniques used were only partially described, especially how to address internal opening[s]
of the fistula, and included technical variations. The pooled rate of primary healing among
the studies was 68% [95% CI: 53.0–84.0%]. No postoperative complications or faecal
incontinence was observed, although not all studies reported these outcomes.
The role of over-the-scope clip [OTSC] in the treatment of anal fistulae in CD has only been
investigated in several small observational case series, often with mixed populations; the
majority were cryptoglandular cases and fewer were CD-related fistula. Mennigen et al.

reported a case series of 10 patients including data on 6 patients with CD.81 A total of 4/6
[66.7%] patients were on biologic therapy at the time of OTSC and all these patients
achieved fistula closure; only 1 patient not receiving biologics healed. Although no
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postoperative morbidity or faecal incontinence was observed, the OTSC may be
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spontaneously passed [2/6, 33%] or need to be subsequently removed due to discomfort
[1/6, 16.7%]. A study by Prosst and Joos reported OTSC in 100 patients (11 had
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inflammatory bowel disease [IBD]) with a closure rate of 45% in IBD. 82 Overall, the OTSC
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was spontaneously passed in 18 patients and appeared to be associated with a lower fistula
closure rate of 33% [6/18 patients]. The OTSC needed to be removed or operatively
explanted in 14 patients. No significant postoperative morbidity or faecal incontinence was
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reported. Although OTSC appears to be safe and may result in fistula closure in some
patients, widespread adoption of this technique is currently limited by a paucity of data in
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CD.
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We recommend against use of chronic seton treatment as the sole treatment for
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perianal CD fistulae other than as palliation [EL3]

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We recommend against a cutting seton due to the risk of incontinence [EL5]
There are no RCTs or studies comparing seton drainage with no treatment for perianal CD
fistulae. Two systematic reviews, including 10 studies [n = 305 patients] on patients treated
solely with seton drainage, reported varying results.83,84 Complete closure rates ranged from
13.6–100% and recurrence rates from 0–83.3%. Timing of seton removal differed among
studies [range 3 weeks to 40 months]. Included studies were prospective and retrospective
cohort studies and case series and mostly of questionable quality.
Additionally, the PISA trial published in 2020 compared the following three treatment
strategies: long-term seton drainage alone, anti-TNF treatment, and surgical closure [the
latter two with prior seton drainage].85 The study was stopped by the data safety monitoring
board because of futility. Seton treatment was associated with the highest reintervention rate
[10/15 seton vs 6/15 anti-TNF vs 3/14 surgical closure patients; p = 0.02]. No substantial
differences in perianal disease activity and quality of life were observed between the groups.

Interestingly, in the accompanying PISA prospective registry, inferiority of chronic seton
treatment was not observed for any of these outcome measures. This study suggested that
chronic seton treatment should not be recommended as the sole treatment for perianal CD
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fistulae.
ip
The cutting seton, in which a non-absorbable thread is inserted into the fistula tract and
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exteriorized through the anorectal canal with subsequent tightening, causing gradual cutting
through the anal sphincter, should not be used as many studies have shown associated
us
complications, including prolonged perianal pain and incontinence rates up to 58%.84
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3.3. Combined approaches
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d

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We recommend seton drainage preceding medical or surgical therapy for complex

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perianal CD fistulae [EL3]

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Combined anti-TNF therapy and seton removal could result in improved healing rates,
faster time to healing, longer time to relapse, and a reduced need for surgery than
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either therapy alone [EL3]
There were no RCTs comparing medical or surgical therapy with or without preceding seton
drainage. Five systematic reviews were included.83,84,86-88 Most studies focused on anti-TNF
therapy. One of the largest systematic reviews [42 studies] included studies assessing anti-
TNF agents for perianal fistulae. In most studies, anti-TNF was combined with preceding
seton placement and it was suggested that combining seton drainage with an anti-TNF
agent was superior. These results are consistent with another large systematic review that
revealed that a combination of surgical treatment [including seton drainage] with medical
therapy [anti-TNF agents and immunomodulators] may have additional benefit on healing of
perianal CD fistulae compared with surgery or medical therapy alone.88 One study showed
that 75% of patients treated with anti-TNF therapy after prior seton placement healed
compared with 63% of patients without initial seton.89 Another study revealed that patients
with seton placement prior to anti-TNF therapy had a better initial response [100% vs 82.6%;

p = 0.014], lower recurrence rate [44% vs 79%; p = 0.001], and longer time to recurrence
[13.5 vs 3.6 months; p = 0.0001] compared with patients receiving infliximab alone.90
Additionally, patients with seton placement prior to anti-TNF therapy were less likely to
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require hospitalization and had reduced healthcare costs.87 Studies have also shown shorter
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mean time to healing,91,92 longer time to relapse,92 and reduced need for repeat surgery93
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than with either therapy alone.
Timing of seton removal is largely variable and inconsistent between studies, ranging from
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4–27 weeks post insertion.93,94 However, the heterogeneity and low quality of the mainly
retrospective studies included should be considered.
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In most studies, seton drainage was performed prior to surgical closure in patients with
perianal CD fistulae. However, several small retrospective studies showed no association
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between fistula healing rate after a LIFT procedure and prior seton placement or duration of
seton drainage prior to surgery.71,95
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A recent retrospective study analysed medical and surgical therapies to identify the optimal
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care strategy in 200 patients. Seton drainage prior to anti-TNF therapy alone did not
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significantly increase the fistula closure [HR: 1.15; 95% CI 0.61–2.32; p = 0.66]. The
combination of seton placement and anti-TNF therapy followed by fistula closure surgery
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within 52 weeks was the best management strategy for fistula healing in multivariate
analysis [p = 0.02]. Cumulative probabilities of fistula closure following the latter combined
approach were 43.8%, 82.2%, and 93.7% at 1, 3, and 5 years, respectively. Patients
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concomitantly treated with a combination of anti-TNF therapy and immunosuppression at

surgery had the highest long-term closure rate.96
Importantly, especially in case of perianal sepsis, adequate seton drainage seems to be of

key importance to create optimal circumstances prior to starting medication or proceeding to
surgical closure.
We recommend the combination of medical therapy with surgical fistula closure in

amenable patients with complex perianal fistulae, as surgical closure results in
improved long-term outcomes [EL3]

Two RCTs and one retrospective study investigated surgical closure of the fistula tract in
combination with medical therapy. A first multicentre RCT compared seton removal and
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surgeon’s choice of closure with seton removal alone in patients treated with adalimumab.
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There was no difference in clinical closure at 12 months [surgery 56.3% vs control 65.4%; p
= 0.48] or in secondary outcomes measuring quality of life, continence, and AEs. Patients
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with surgical closure experienced longer disease duration and were more likely to have been
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previously treated with infliximab, suggesting more aggressive disease. Most patients [79%]
were treated with fibrin glue with limited efficacy in perianal CD. In addition, the study was
underpowered and robust conclusions could not be drawn from these data.97
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Ninety-four patients were enrolled [38 patients with surgical closure and 56 with anti-TNF
therapy] in the patient preference PISA II trial.98 At 18 months, radiological healing was
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significantly more common after surgical closure (12/38 [32%] patients) than after anti-TNF
therapy (5/56 [9%] patients) [p = 0.005]. Clinical closure was not significantly different
d
between the two treatments [68% vs 52%, respectively; p = 0.076]. Fewer patients required
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a reintervention and the perianal disease activity index was significantly lower after surgical
closure. Long-term results after a median follow-up of 5.7 years showed no recurrences in
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patients with radiological healing; recurrence was observed in 41% of patients with clinical
closure without radiological healing.99
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A retrospective study of 226 patients found no difference in healing when patients underwent
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a variety of surgeries alone compared with those undergoing surgery with concurrent
infliximab [60% vs 59%, respectively]. Surgical procedures included seton drainage [50%],
fistulotomy [41%], fibrin glue [6%], advancement flap [2%], and collagen plug [1%]. However,
time to healing was 6.5 months after combination therapy [surgery and infliximab] and 12.1
months after surgery alone [p < 0.0001].91
There are conflicting data on allogenic adipose-derived stem cell therapy for the
induction and maintenance of remission in complex perianal fistulae in CD [EL5]

The efficacy of MSC in treatment of perianal fistulae CD is mediated by anti-inflammatory
properties and by the capacity to engraft and transdifferentiate into healthy tissue.100
Allogenic MSC from adipose tissue (Cx601-darvadstrocel; Alofisel®) was assessed in a
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phase 3 RCT that included 212 patients with refractory fistulizing perianal CD.101 At week 52,
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a significantly higher proportion of patients treated with darvadstrocel achieved combined
remission when compared with controls [56.3% vs 38.6%; 95% CI 4.2–31.2; p = 0.010].
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Combined remission was defined as closure of all treated external openings at clinical
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examination and absence of collections >2 cm at MRI. A study extension including 40
patients was prospectively conducted through week 104.102 Clinical remission was reported
in 14/25 [56%] patients in the darvadstrocel group and 6/15 [40%] patients in the control
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group, which was not statistically significant [95% CI: -15.5 to 47.5]. No serious AEs were
reported at week 52 or week 104. Due to the high cost of darvadstrocel, the costs and
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potential benefits should be considered on a case-by-case basis of the clinical situation.
A meta-analysis published in 2018 that included three studies suggested that MSC of
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different origin significantly improved healing of perianal fistulae when compared with control
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at 6 to 24 weeks (odds ratio [OR]: 3.06; 95% CI: 1.05–8.90; p = 0.04) and numerically at 24
to 52 weeks [OR: 2.37; 95% CI: 0.90–6.25; p = 0.08].103 No significant increases in AEs [OR:
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1.07; 95% CI: 0.61–1.89; p = 0.81] were observed in treated patients. Limitations of the
available studies on MSC in perianal CD include heterogeneity in protocols [allogenic or
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autologous MSC, bone-marrow or adipose tissue-derived MSC], low number of patients,

varying definitions of fistula healing, and lack of consensus on definition of perianal fistula
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healing in MRI. Further studies based on robust well-defined radiological targets are needed
to evaluate the role of MSC on the natural history of perianal fistulizing CD. Results from the
phase 3 RCT ADMIRE-CD II will provide additional information.104 Although the results of the
ADMIRE-CD II were not yet published at the time of writing the present guidelines, the
sponsor announced in a press release dated 17 October 2023 that the primary endpoint of
combined remission at 24 weeks in complex perianal CD fistulae treated with darvadstrocel
was not met. These inconclusive results were also presented at ECCO 2024 on 23 February
2024. The safety profile for darvadstrocel was consistent with prior studies and no new
safety signals were identified. The final results of ADMIRE-CD II will help position this
treatment in the management of complex perianal fistulae in CD.

We suggest autologous adipose-derived stem cells may be used as a treatment

option in complex perianal CD [EL4]
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There is insufficient evidence to recommend use of platelet-derived factors or stromal
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vascular fraction in complex perianal CD [EL5]
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Autologous stem cells [ASC] have the advantage of originating from the patient undergoing
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treatment, as opposed to donor-based therapy, thus making ASC readily available and less
costly. ASC may be injected in a similar manner as allogenic MSC, mixed with fibrin glue, or
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loaded onto a fistula plug.
The most recent systematic review summarizing results of four RCTs demonstrated
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increased clinical healing rates of ASCs when compared with control patients treated with
fibrin glue alone [OR: 3.19; 95% CI: 1.05–9.65; p = 0.04].105 Unfortunately, it is difficult to
e
draw firm conclusion for patients with CD, as only 20 patients with CD were included in these
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studies and most patients had a short follow-up of only 8 weeks. There are no studies that
directly compared autologous to allogeneic stem cells for perianal CD fistulae.
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The best evidence on the use of ASCs for perianal CD fistulae comes from various
prospective case series including a total of 110 patients.106-111 Although treatment protocols
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varied substantially, most involved curettage of the fistula tract, suturing of the internal
opening [with or without an advancement flap], and filling of the fistula tract with ASCs. Most
studies allowed a second injection of ASCs in patients with incomplete closure. Clinical
healing rates, defined as no suppuration from the external orifices, ranged from 33–91%.
However, most of these series lacked an adequate follow-up [range 2–12 months] with
recurrence rates rarely described. The largest study included 30 patients and showed a
closure rate of 83.3% with a recurrence rate of 33%.110
Despite the additional requirement of harvesting cells via liposuction to obtain ASC, the
procedure appeared safe. The most common AEs were postoperative pain, abscess, or
bleeding.105 There were no significant differences in AEs when compared with the control
group [OR: 1.06; 95% CI: 0.71–1.59; p = 0.77].
There are also some studies that investigated the effects of injecting freshly collected

microfragmented autologous adipose tissue, platelet-derived growth factors, or stromal
vascular fraction into perianal CD fistulae.109,111,112 Feasibility was demonstrated in most
patients and results appeared comparable to ASCs, with clinical healing ranging from 38–
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67%. Harvesting, preparation, and administration of these tissues are described as easy,
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inexpensive procedures with minimal AEs. Again, these series suffer from small patient
numbers and brief follow-up and lack description of recurrence rates. Further studies are
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required to define the true potential of these approaches.
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an
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We suggest medical treatment in anogenital and rectogenital CD fistulae and

counselling for surgical closure in selected patients with CD [EL5]
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Anogenital and rectogenital fistula are complex and disabling conditions that are better
managed by an experienced multidisciplinary team. No RCTs or prospective studies were
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found that compared anti-TNF agents alone versus anti-TNF agents and surgery combined
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to treat these fistulae.
A post hoc analysis of the ACCENT II study identified 25 women with ano- or rectovaginal
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fistulae.113 This study demonstrated that infliximab is more effective than placebo in
prolonged closure [defined as non-draining fistula at week 14]; 13/29 [44.8%] fistulae
responded to induction regimen with infliximab and were closed. From weeks 14 to 46,
among responders in the infliximab maintenance group, the proportion of rectovaginal
fistulae that closed ranged from 54.5–90.0% compared with 28.6– 42.9% in the placebo
group.
A French retrospective multicentric observational study including 131 consecutive patients

treated with anti‐TNF agents for 1 year found that 37% of patients had complete clinical
fistula closure, 22% had partial response, and 41% had no response.114 Complementary
surgery was allowed, including advancement flap [rectal, vaginal, or Martius flap], fibrin glue,
collagen plug, or gracilis muscle interposition and performed during the first year in 10
patients [8%], translating into a higher closure rate in multivariate analysis [adjusted RR:
2.02; 95% CI 1.25–3.26; p = 0.004]. A retrospective study of 166 patients who underwent
operations for anogenital fistulae revealed an overall fistula healing rate of 71.7% [n = 119]
with a median follow-up of 5.5 [1.2–9.8] years.115 Nearly one-third of patients [33.1%]

achieved complete healing after first surgery, 51.8% [n =86] after the second, and 62.1% [n
= 103] after the third operation.
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A recent systematic review found nine studies that reported healing, success, or closure
ip
[range 14–81%] across multiple surgical procedures; seven studies reported success rates
ranging from 50–75%.116 However, those studies were of low quality and had limited sample
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sizes, various concomitant medical therapies, heterogenous fistula and patient
characteristics, outcomes considered, and definition of outcomes.
us
an
M
We suggest faecal diversion with a defunctioning ileostomy or colostomy for

treatment of refractory, complex perianal CD [EL4]
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Patients with treatment-refractory perianal CD may benefit from faecal diversion [FD] with a
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diverting ileostomy or colostomy. Indeed, FD is associated with a high early clinical response
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rate and an improved quality of life, although FD often becomes permanent. A systematic
review of 16 retrospective studies with 556 patients with perianal CD found that FD is
associated with early clinical response in 63.8% [95% CI: 54.1–72.5%].117 However, stomas
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were often permanent and only 16.6% [95% CI: 11.8–22.2%] of patients ultimately had
successful ostomy reversal. The rate of proctectomy after failure of temporary diversion was
41.6% [95% CI: 32.6– 51.2%]. Proctitis was associated with increased risk of permanent
diversion.
One study compared FD plus local procedures for perianal CD [n = 13] to local procedure
without FD [n = 26].118 Complete resolution of perianal CD was observed in 11 [85%]
patients with FD versus 5 [19%] patients without FD. Of the FD patients, 6 [46%] had stoma
reversal, of whom 3 [50%] remained disease free, 1 [17%] required successful additional
local procedures, and 2 [33%, 15% overall] required re-diversion. Thus only 4/13 [31%] of
FD patients ultimately had stoma reversal. Another study of 21 patients showed that
although some patients may achieve complete healing, many do not; initial improvement
was followed by plateau in 7 [33%], temporary improvement in 6 [29%], no effect in 4 [19%],
and healing in 4 [19%] patients.119 In this study, 11 [52%] patients subsequently had
proctocolectomy, 6 [28.6%] had their stoma in situ, and 4 [19%] had stoma reversal. In a

large series of 138 patients who had initial FD, a total of 63 [45%] underwent subsequent
total proctocolectomy, 45 [33%] had their stoma without proctectomy, and 30 [22%] had
stoma reversal.120 Independent predictors of lack of stoma reversal included proctitis [OR:
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7.5; 95% CI: 2.4–33.4], 1–2 seton placements [OR: 3.3; 95% CI: 1.4–8.8], and >2 seton
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placements [OR: 6.9; 95% CI: 1.2–132.5]. Biologics were not associated with stoma closure
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[p = 0.25].
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Few studies examined quality of life before and after FD in perianal CD. In a series of 34
patients with FD, compared with similar patients without FD, patients with FD had fewer
perianal CD symptoms [44% vs 79%; p < 0.05], higher Gastrointestinal Quality of Life index
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scores [68 vs 62 points; p < 0.001], and higher GI symptoms sub-scores [81 vs 67; p <
0.0001] compared with non-diverted patients.121 The most recent meta-analysis evaluating
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1578 patients managed in the biologic era similarly concluded that FD improved symptoms
and quality of life, while bowel continuity could be successfully restored in a quarter of the
patients.122
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We suggest proctectomy for treatment of refractory, complex perianal CD despite

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defunctioning stoma [EL4]
Proctectomy may be recommended in many patients with perianal CD. However,

proctectomy is associated with a substantial risk of a non-healing perineal wound in the
short-term and a risk of colonic or small-bowel recurrence in the long-term. In a series of 127
patients with perianal CD, proctectomy was required in 32 [25.2%] patients.123 Several
studies discussed independent risk factors for proctectomy, including age at first perianal
fistula [p < 0.02], perianal fistula at the time of CD diagnosis [p < 0.04], >3 fistulae during
follow-up [p < 0.01], and proctitis [p < 0.0001].124 Other studies also reported malignancy in
the setting of perianal CD as an indication for an oncologic proctectomy.124-126
Proctectomy for perianal CD is typically performed as an abdominoperineal resection [APR]

with a colostomy or as a total proctocolectomy with end-ileostomy in case of extensive
colonic involvement.123-128 In terms of extent of bowel resection in the setting of perianal CD,

a single study examined APR with colostomy and reported a clinical recurrence rate of
colonic CD of 22% for an endoscopic colonic recurrence rate of 29%; overall 5% of patients
required completion total colectomy.128 It is important to note that proctocolectomy does not
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cure CD; a multicentre retrospective study of total proctocolectomy with end-ileostomy
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including 193 patients with refractory perianal CD reported a 23% small-bowel recurrence
within 2 years.127 Independent risk factors for recurrence included CD diagnosis at age <18
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years [HR: 2.56; 95% CI: 1.40–4.71] and previous small-bowel resection [HR: 2.61; 95% CI:
1.42–4.81].
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Proctectomy for IBD is often performed as an inter-sphincteric dissection, limiting the size of
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the perineal incision.123-128 The inter-sphincteric groove may not be identifiable due to
scarring in up to 78% of patients with perianal CD, limiting the ability to perform an inter-
sphincteric dissection and impacting wound healing.126 Indeed, delayed perineal wound
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healing is often observed after proctectomy in perianal CD.125,129-132 When wounds are left
open to heal by secondary intention, an uncommon practice nowadays, only 58% of perineal
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wounds of patients with IBD were healed after 6 months of dressing changes.130 Wound
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irrigation has also been explored in the 1980s and half of perineal CD wounds were healed
at 30 days compared with 87% after APR for cancer in the absence of radiotherapy.132 Male
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gender was a risk factor for delayed healing, especially when the drain exited through the
wound instead of laterally. Higher success rates were observed when myocutaneous flaps
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were used, although patients are still at risk for subsequent fistulization [20% in a small
study].131 In a large series of 126 patients, 72 [53%] wounds were healed at 12 weeks, while
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delayed healing was observed in 35 [26%] and non-healing in 29 [21%] patients.125

Preoperative perianal sepsis was an independent predictor of a delayed- or non-healing
wound [p = 0.001], suggesting FD prior to proctectomy.129 For non-healing perineal wounds
with metastatic CD, hyperbaric oxygen therapy may be an option.133
Practice Points
Fistula treatment should start with insertion of a seton followed by medical treatment
[preferably anti-TNF]. In the absence of proctitis, patients should be counselled for surgical
closure.

Perianal fistulae in CD can have a substantial detrimental impact on patient quality of life.
Current biological understanding of perianal fistulizing CD remains inadequate and previous
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classification systems have not provided clear guidance on therapy in clinical practice. A
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new classification presented in Figure 1 identifies four groups of patients.134 Key elements
include stratification according to disease severity and desired outcome. This classification
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can guide patients and clinicians in decision making on a ‘treat to patient goal basis’ by a
combined medical and surgical approach.
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All treatment should start with insertion of a seton to control sepsis and create a patent tract,
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followed by medical treatment [preferably anti-TNF with high trough level]. After good
response to anti-TNF therapy, seton removal can be considered within 2–8 weeks to aim for
closure with medication only.135 Although clinical closure can be achieved in up to 60% by
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medication, it should be noted that MRI closure is rare [<10%] with high risk of recurrence
and surgical reintervention.98 MRI closure is more frequently seen after surgical closure
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under anti-TNF therapy [up to 40%], with no recurrences after long-term follow-up in case of
a completely fibrotic tract on MRI.99 Therefore, in absence of proctitis, amenable patients
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should be counselled for surgical closure. For patients with an inter-sphincteric or low trans-
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sphincteric single fistula tract, fistulotomy can be considered as this procedure will have the
highest success rate.
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In case of complex perianal fistulae, AF or LIFT can be offered, depending on fistula

characteristics. Stem cells can be an alternative, especially in patients with multiple internal
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openings or pre-existing complaints of incontinence.
In case of anti-TNF failure and surgically refractory fistulae, more experimental approaches
[such as hyperbaric oxygen therapy or new medical approaches] can be attempted, ideally in
the context of a prospective clinical trial. An algorithm to guide the management of perianal
CD is illustrated in Figure 2.
4. Surgical management of abdominal Crohn’s disease
4.1 Preoperative optimization

We recommend elective bowel resection over emergency surgery in patients with CD
[EL2]
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A meta-analysis of cohort series including 75’971 CD patients from 15 countries reported a
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significantly lower mortality among patients who underwent elective [0.6%; 95% CI: 0.2%-
1.7%] vs emergent surgery [3.6%; 95% CI: 1.8%-6.9%], highlighting the importance of
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perioperative optimization and avoidance whenever possible of emergent surgeries136.
Statement 4.2 ECCO CD Treatment GL [2024] us

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Pre-operative optimization should be initiated, followed by re-assessment of the
patient for surgical intervention [EL3]
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A recent meta-analysis showed that emergency bowel resection is associated with a higher
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risk of overall postoperative complications and abdominal septic complications.137 This is

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consistent with a European Society of Coloproctology prospective snapshot audit in which

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emergency surgical intervention was associated with unfavourable postoperative

outcome.138 Another recent multicentre international observational study concluded that
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emergency intervention in patients with an abdominal abscess increased the risk of

postoperative complications and abscess recurrence.139 Moreover, patients undergoing
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emergency surgery for CD have a higher rate of stoma formation.140,141 Lastly, laparoscopic
surgery in the emergency setting has a higher conversion rate and involves resection of
longer segments of small bowel, which is a concern in CD due to a lifetime risk of short
bowel.140
The drivers behind these unfavourable outcomes may be patient status and the environment
of care typical of an emergency situation. Emergency resection [within 48 hours of
admission] is performed on tissue characterized by profuse oedema and acute inflammation
in a patient often in an unstable condition by a team that may not be specialized in IBD or
even colorectal surgery. Patients with CD who undergo emergency operation typically have
a severe form of disease, are malnourished, and are often on steroids, immunomodulators,
biologicals, or combinations thereof with a higher likelihood of undrained abscesses, fistulae,
or both at time of emergency surgery. Drainage of an abscess and relieving obstruction
together with preoperative optimization should be initiated immediately on admission, as
described in recent prospective cohort series142,143 and advised in ECCO topical
reviews.144,145

Preoperative optimization of an emergency CD patient and transfer of care from the acute to
the specialized/elective setting is key to improving short- and long-term postoperative
outcomes. On the other hand, free bowel perforation is one of the few situations where
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urgent surgery may be mandatory as bowel perforation is a very rare but serious and
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potentially life-threatening complication in CD. The literature is characterized by low-quality,
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heterogenous studies based on historical data. A study from Korea estimated the incidence
to be 2.15% in the Korean CD population.
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There are two important points to consider when CD leads to bowel perforation.
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1. Bowel-wall thickness: Bowel-wall thickening in CD occurs due to chronic inflammation
and scarring and differs from ischaemic bowel perforation, which occurs when there is a
decreased blood supply to the bowel, potentially resulting in a perforation. Symptoms,
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diagnostic approach, and treatment may also differ between these conditions.
2. Size of perforation: Bowel perforation in CD can vary in size and presentation. While
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some cases may involve small or microscopic perforations, others can present as larger
perforations. Timely diagnosis and appropriate treatment can prevent further
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complications and improve outcomes.

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A small-bowel perforation can, in very selected situations and under supervision of an

experienced colorectal surgeon, be managed conservatively. This mandates a very close
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clinical follow-up and the capacity to operate immediately should the patient deteriorate.
The early involvement of a multidisciplinary team consisting of an IBD gastroenterologist, an
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IBD surgeon, a radiologist, and a dietician is mandatory in emergency presentation of CD

due to the complexity of the disease and management.
We recommend control of sepsis prior to abdominal surgery for CD [EL3]

We suggest use of intravenous antibiotics and percutaneous image-guided drainage

as the first-line treatment for intra-abdominal abscesses related to CD [EL3]

We suggest conservative treatment following successful percutaneous image-guided

drainage of an intra-abdominal abscess in carefully selected cases. A low threshold
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for surgery is recommended in the event of medically refractory cases [EL4].
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Penetrating CD complicated by intra-abdominal abscesses [IASC] represents a complex
condition requiring involvement of interventional radiologists, gastroenterologists, and
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surgeons. An [elective] operative approach appears indicated in most patients, as
conservative management leads to complete abscess resolution in less than 30% of
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selected cases, while delayed elective surgery is associated with improved postoperative
outcomes, avoidance of a stoma, and abscess recurrence.146,147 148
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Observational studies indicate that failure to control IASC preoperatively increases the risk of
postoperative complications, anastomotic leaks, postoperative sepsis, and stoma formation,
resulting in an increased length of hospital stay.139,149-151 Percutaneous drainage [PD] under
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ultrasonographic or CT guidance may be the primary approach for treatment of well-defined

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abscesses. Successful drainage rates of 74–100%, allowing avoidance of emergency

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surgery in 14–85% of patients, were reported.18 PD with antibiotics to control IASC resulted
in better quality of life than surgery alone, provided abscesses were completely
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drained.139,149,152 PD and antibiotic therapy should be combined with perioperative

optimization, including nutritional support and stopping or decreasing corticosteroids.
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Despite PD, these patients still present with higher morbidity than those without preoperative
IASC.140
It is worth noting that when performed by specialized high-volume IBD surgeons, early
laparoscopic surgery [<1 week after admission] was safe, feasible, and associated with
similar morbidity rates when compared with delayed surgery [within 3 weeks after initial
admission, including PD in 28% of patients].153 However, steroid treatment before PD and
short waiting interval [<2 weeks] were associated with a higher risk of abscess recurrence,
while anaemia and long waiting interval [>4 weeks] increased the risk of stoma
construction.153 Overall, performing surgery 2–4 weeks after successful PD was associated
with the lowest risk of postoperative IASC.139 Identifying patients who may be treated without
surgery is challenging and currently relies on clinical judgment rather than on evidence. In
general, medically refractory disease, presence of stenosis, or an enterocutaneous fistula
represent clear indications for surgery.152

We recommend endoscopic balloon dilatation as a treatment option for small-bowel
strictures <5 cm in length when technical expertise is available [EL2]
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In a review of 1463 patients with CD who underwent 3213 endoscopic balloon dilatation
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[EBD] procedures, a stricture length <5 cm was mostly amenable to EBD and associated
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with a surgery-free outcome; every additional centimetre in stricture length increased the
need for surgery by 8% [p = 0.008].154 This is consistent with other reviews.155-157
Inflammation, disease activity, type of stricture, balloon diameter, and duration of inflation did
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not affect outcomes.154,156
While therapeutic success can be achieved after a single dilation, several dilations may be
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necessary to resolve obstructive symptoms; however, repeat dilation may reduce quality of
life.158,159 Although accessory endoscopic techniques, including local steroid injection, cutting
procedures [e.g. Argon beaming], and stent implantation have been proposed to improve
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resolution,154 the evidence is weak. Some retrospective cohort studies suggested that
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combined therapy with anti-TNF and EBD may prevent intestinal stricture recurrence and
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surgery in hospitalized patients with CD.160,161

An unresolved controversy is the dilation efficacy of primary versus anastomotic strictures.
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Identification of predictive factors for the long-term success of EBD may assist clinical
decision making and an individualized treatment approach in stricturing CD.162
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In conclusion, short-term therapeutic success of EBD is high in a selected group of patients

when technical expertise is available. However, the impact on long-term quality of life, need
for repeat dilations, and strictureplasty or bowel resection is less clear.
Practice point
Whenever possible, elective surgery is preferable to an emergency procedure in both

fistulizing and obstructive CD. The control of IASC is multidisciplinary and draws from
interventional radiology, infectious disease, gastroenterology, and surgery. Imaging
[sonography, CT, MRI], swift drainage, antibiotics, intensified perioperative therapy, and
specialist care are the mainstays of treatment. PD is mostly a bridge intervention rather than
a definitive solution; elective surgery performed 2-4 weeks thereafter minimizes
postoperative complications and need for a stoma.
Primary conservative management of bowel obstruction includes rehydration, nasogastric

decompression, imaging, and consideration of high-dose steroid therapy. Frequent
monitoring and surgical consultation are critical. Surgery can be deferred in most cases but

should be considered during follow-up. Definitive non-surgical management may be
successful but must be carefully balanced and discussed with the individual patient.
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We recommend preoperative nutritional assessment and identification of nutritional
risk by IBD-dedicated dietitians for patients with CD who need surgery [EL2]
us
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When feasible, enteral nutrition should be the strategy of choice for preoperative
optimization in patients with CD [EL3]
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Malnutrition is common in patients with CD requiring surgery and is a risk factor for adverse
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postoperative outcomes and complications. Systematic nutritional risk screening [body mass
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index, unintentional weight loss, reduced dietary intake,

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illness severity] together with perioperative nutritional support may mitigate the perioperative
risks associated with malnutrition. An ECCO consensus and topical review on perioperative
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dietary therapy in CD concluded than exclusive enteral nutrition [EEN] represented a valid
preoperative optimization strategy for reducing complications and improving nutritional status
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in patients with CD, likely by modulating inflammatory status and improving microbial
composition.145,163-165
The benefits of preoperative EEN have been consistently reported, leading to a marked
reduction of postoperative morbidity [21.9% vs 73.2%; OR: 0.09; 95% CI: 0.06–0.13; p <
0.01], although data on biochemical optimization are still debatable.166-168 Conversely, the
role of parenteral nutrition [PN] in the preoperative optimization strategy is more debated. 169
Importantly, EEN requires dedicated nutritional support and high patient compliance to be
successful.
The use of PN in the perioperative period should be reserved for patients unable to tolerate
EEN, do not meet their nutritional requirements with EEN, or in which EEN is
contraindicated.170 In a recent prospective multicentric cohort study, preoperative EEN
reduced morbidity for infection and temporary stoma requirement in malnourished patients
with CD 164 . In another recent cohort study, patients receiving preoperative PN had
significantly lower rates of non-infectious complications [OR: 0.07; 95% CI: 0.01–0.80; p =

0.03]. A subset of frail patients with severe CD who did not tolerate EEN and required PN
presented a similarly high rate of IASC and primary stoma as when upfront surgery was
elected. Hence, the advantage of providing PN to this subgroup of frail patients is
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questionable, as these patients may benefit from an early surgical approach followed by
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nutritional replacement.171 Therefore, early surgery with postoperative optimization may be
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considered in frail, severely ill patients who do not tolerate EEN and accept a diverting
stoma.
us
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We recommend that steroids should be tapered whenever possible before surgery to
reduce the risk of complications [EL2]
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Previous ECCO guidelines have reported that treatment with >20 mg prednisolone daily for
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>6 weeks increases the risk of postoperative septic complications.11,18,172 Whilst there is no
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large RCT confirming this position, one large multicentre cohort study and numerous
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retrospective cohort studies have identified this risk [summarized in 3 meta-analyses].173-175

Indeed, preoperative steroid use was a significant risk factor for major complications,
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including an overall increased risk of postoperative complications [OR: 1.41; 95% CI: 1.07–
1.87] and a specifically increased risk of postoperative IASC [OR: 1.68; 95% CI: 1.24–
2.28].174,176 Patients who received >40 mg perioperative oral steroids had the highest risk of
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overall complications [OR: 2.04; 95% CI: 1.28–3.26]. A meta-analysis confirmed an almost
doubling of total wound infections [OR: 1.70; 95% CI: 1.38–2.09].173 Similar to the results
from the large multicentre cohort study, an increased risk for anastomotic leak was also
observed [OR: 1.51; 95% CI: 1.02–2.25].175
Steroids should be reduced before surgery as part of a preoperative optimization strategy in
combination with nutritional optimization and drainage of sepsis. If this is not possible,
consideration should be given to a staged procedure with a temporary stoma.

We recommend against cessation of biologics prior to surgery as current evidence
suggests that preoperative treatment with anti-TNF therapy [EL3], vedolizumab [EL3],
and ustekinumab [EL4] does not increase the risk of postoperative complications in

patients with CD undergoing abdominal surgery
Anti-TNF therapy
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Use of biologicals in patients with CD undergoing surgery remains controversial. Concern
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exists over the desired modulation of the immune response and the potential to increase
postoperative complications. Several retrospective studies regarding anti-TNF agents have
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been published over the last 20 years. Some suggested an increased incidence of
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complications in patients receiving anti-TNF agents preoperatively and other studies showed
no difference. Several meta-analyses have also reported varying conclusions.177 Several
prospective studies also reached inconsistent conclusions. This variation probably
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represents heterogenous populations, different outcomes, and inconsistent definitions of
outcomes. Most evidence is concentrated on infliximab and adalimumab.177 The PUCCINI
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trial is the largest prospective trial to date and revealed no difference in the rate of any
infection between patients using biological therapy and those not.178 Detectable preoperative
serum concentrations of anti-TNF agents also did not increase the risk of surgical site or
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overall infection rates.178 Hence, anti-TNF therapy can be continued prior to surgery.
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Vedolizumab
Although initial retrospective data suggest that VDZ leads to an increased risk of
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postoperative infection, subsequent studies showed no increased risk. These data were
confirmed by most, but not all, recent meta-analyses.179-182 The latest of these showed no
significant differences in overall complications [OR: 1.04; 95% CI: 0.48–2.24],180 infectious
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complications [OR: 1.00; 95% CI: 0.37–2.69], or surgical site infections [OR: 1.45; 95% CI:
0.33–6.32] for those receiving VDZ preoperatively. Therefore, VDZ can be continued prior to
surgery.
Ustekinumab
Although one meta-analysis focused on ustekinumab and postoperative complications, the
comparator was patients receiving anti-TNF therapy.183 No difference in complications and
infectious complications were identified. The only cohort study comparing ustekinumab with
non-biological therapy revealed that preoperative use of ustekinumab is an independent risk
factor for intra-abdominal sepsis [OR: 2.93; 95% CI: 1.16–7.40; p = 0.02].184 Although further
studies are required to confirm the safety of ustekinumab and surgery, current data suggest
that cessation before surgery may not be necessary.
There is no available evidence of the possible impact of preoperative use of CZP,

rizankizumab, or JAK inhibitors on postoperative morbidity in patients with CD undergoing
abdominal surgery. The safety of continuing newer biological agents prior to surgery remains
unknown.
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Practice points
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Preoperative optimization is a key element in successful management of complex situations
and chronic disease. Many aspects of optimal perioperative care are generic and common to
of CD [venous thromboembolism prophylaxis, us

all abdominal procedures,185 although some aspects are particularly important in the context
nutrition, iron management, drug
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management, minimally invasive approaches, and bowel- and sphincter-sparing
techniques].186,187 While high-dose steroids should be tapered to reduce surgical morbidity,
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current biological therapy can safely be continued perioperatively.

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4.1 Surgical techniques

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We recommend a laparoscopic approach as the first line in abdominal surgery for CD

[EL2]
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A Cochrane review of two randomized trials188,189 showed no difference in complications

between laparoscopic and open surgery for CD. A more recent review190 showed a benefit
for patients operated by laparoscopy, with fewer complications and lower rate of incisional
hernia. This review included both randomized trials and observational studies. While this
may potentially introduce some bias, based on strong evidence for the benefits of
laparoscopy, especially in relation to reduced adhesions, the current evidence
strongly supports recommending laparoscopy as the first-line approach. Laparoscopic
resection for recurrent CD is also feasible but is associated with higher risk for conversion.191
Importantly, in the absence of expertise to perform laparoscopic surgery, emergency
operations should not be delayed.

We recommend laparoscopic resection as an alternative to infliximab [EL2] or

adalimumab [EL4] therapy in patients with limited terminal ileal or ileocecal disease
A randomized, controlled, open-label, multicentre trial assigned 143 patients with non-
t
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stricturing CD of the terminal ileum to receive either laparoscopic ileocecal resection [n = 73]
or infliximab [n = 70]. At 12-month follow-up, quality of life and body-image perception were
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comparable.192 Patients treated with infliximab had fewer days of sick leave from work.
Serious complications related to treatment occurred in 4 resected patients versus 2 in the
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anti-TNF group. Crossover among groups was needed in 37% of patients treated with
infliximab and in 26% of those who underwent surgery. Long-term data from the randomized
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trial revealed no surgical recurrence in the surgery group after 5 years, while 50% in the anti-
TNF group had surgery at 5 years.193 A recent meta-analysis suggests reduced risk of
overall and surgical recurrence and reduced use of postoperative biologic therapy if surgery
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is performed early.194 Based on these data, early surgery has a benefit in patients with
limited terminal ileal CD and represents a reasonable alternative to escalating medical
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therapy. Patients should be advised early about a surgical option.

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We suggest stapled side-to-side anastomoses in small-bowel or ileocolic resections
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for CD [EL3]
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Surgeons place great importance on the technical aspects of their work, which can be
influenced by various factors, including their training, personal experience, available
resources, and the clinical scenario. The choice of the optimal anastomosis technique in
small-bowel and ileocolic resections has been a subject of controversy. In recent years,
there has been a growing body of evidence supporting the use of side-to-side anastomosis,
and this support has been consistent over time.
A significant meta-analysis on 661 patients operated for cancer and CD revealed a
significantly higher anastomotic leak rate in end-to-end anastomoses compared with side-to-
side anastomoses [OR: 4.37; p = 0.02]. This was also observed in the subgroup of ileocolic
anastomoses [OR: 3.8; p = 0.05].195 Furthermore, overall postoperative complications [OR:
2.64; p <0.001] and hospital stay length were higher [by 2.81 days; p = 0.007] when an end-
to-end anastomosis was performed. A subsequent meta-analysis confirmed the superiority
of side-to-side anastomosis in overall postoperative complications [OR 0.6; p = 0.01].
However, there were no statistically significant differences in leak rates, endoscopic and
symptomatic recurrence, or reoperation for recurrence.196

A meta-analysis compared 396 stapled side-to-side anastomoses with 425 hand-sewn end-
to-end anastomoses and found that stapled side-to-side anastomoses outperformed in all
endpoints, namely overall postoperative complications [OR: 0.54; 95% CI: 0.32–0.93],
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anastomotic leak [OR: 0.45; 95% CI: 0.20–1.00], recurrence [OR: 0.20; 95% CI: 0.07–0.55],
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and reoperation for recurrence [OR: 0.18; 95% CI: 0.07–0.45].197
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A network meta-analysis of 11 trials and 1113 patients further substantiated the superiority
of stapled side-to-side anastomosis regarding overall complications, clinical recurrence, and
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reoperation for recurrence. However, the choice of anastomosis technique did not seem to
affect leak rates, surgical-site infections, mortality, or length of hospital stay.198 A more
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recent systematic review suggested that stapled side-to-side anastomoses may lower the
risk of surgical recurrence in CD, potentially reducing rates of reoperations compared with
hand-sewn end-to-end anastomoses [OR: 0.22; 95% CI: 0.05–0.95].199 In case of
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emergency bowel resection, a retrospective study involving 92 bowel resections

recommended use of stapled side-to-side anastomoses, which was associated with fewer
endoscopic recurrences than hand-sewn end-to-end anastomoses [OR: 38.12; p = 0.01].200
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This was corroborated by another retrospective study.201 However, a recent multicentre,

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retrospective, observational study examining 427 intestinal anastomoses in CD found no

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significant difference in postoperative complications.202

Overall, the quality of the studies included in systematic reviews and meta-analyses was
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notably limited, with only a minority of patients participating in RCTs and heterogenous
populations studied. Despite this limitation, the prevailing consensus leans toward a
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preference for stapled side-to-side anastomosis, which is associated with lower rates of
postoperative complications and allows for an intracorporeal anastomosis. Furthermore, it
was suggested that the diameter of the anastomosis may be a significant risk factor for
recurrence, as a wider anastomosis is thought to be associated with a reduced likelihood of
clinical and surgical recurrences. Importantly, the width of the anastomosis is determined by
its inlet, more than by the length of a staple line or a suture line. Endoscopic appraisal of an
early recurrence should consider the type of anastomosis healing. Indeed, stapled [everted
mucosa] and hand-sewn [inverted mucosa] have a different healing pattern and healing time,
which should neither be confused endoscopically with an early recurrence, nor lead to
overtreatment.

We suggest that the Kono-S anastomosis can be an alternative surgical approach to

other types of anastomoses after ileocecal resection [EL3]
Kono-S anastomosis was first described in 2011 as a new hand-sewn anti-mesenteric
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functional end-to-end anastomosis designed with the aim to reduce anastomotic CD
recurrence after ileocecal resection.
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In the first retrospective study,203 Kono-S anastomosis was associated with a reduction in
both median endoscopic recurrence score [Rutgeerts’ score] and surgical recurrence rate at
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5 years with no safety issues. These findings were then confirmed by a larger international
multicentre retrospective study including 187 patients, reporting a 10-year surgical
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recurrence-free rate of 98.6%.204
Performing a Kono-S anastomosis was associated with longer operative time, similar short-
term outcomes, and likely lower endoscopic recurrence rate than side-to-side
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anastomosis.205 In another two retrospective cohort studies following patients for up to 5

years, Kono-S anastomosis was associated with a lower leak rate than end-to-end
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anastomosis206 or stapled anastomosis207, which in the authors’ opinion could explain the
lower surgical recurrence rate observed in the long term.
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More recently, early results from the first RCT208 comparing Kono-S and side-to-side
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anastomoses demonstrated a significant reduction in the 6-month endoscopic recurrence

rate and mean Rutgeerts’ score, comparable postoperative outcomes, and a trend toward a
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reduced surgical recurrence rate, although this was not statistically significant. This and
other trials are still ongoing with definitive results expected in the near future.
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Several meta-analyses, including the aforementioned RCT and observational studies,

concluded that Kono-S anastomosis was associated with a reduced endoscopic recurrence
rate and comparable short-term outcomes.199,209,210 More limited evidence suggested a
reduction in surgical recurrence and leak rate in Kono-S anastomosis than with conventional
anastomoses. However, the most recent prospective study on Kono-S did not confirm a
reduction in endoscopic recurrence rates and reported similar Rutgeerts’ scores and clinical
recurrence rates between conventional anastomosis and Kono-S.211 Therefore, a definitive
conclusion on the benefit of a Kono-S anastomosis cannot yet be made. Multicentre RCTs
are currently ongoing across the US and Europe and will probably provide definitive answers
on the role of Kono-S anastomosis.212-214

There is insufficient evidence to recommend extensive mesenteric excision in
surgery for ileocecal CD [EL4]
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Extensive mesenteric excision may reduce the incidence of recurrence after resection by
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possibly removing a ‘sump’ of pro-inflammatory substances from the vicinity of the
anastomosis. The current evidence for this is weak. Two systematic reviews addressed
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extensive mesenteric excision199,209 but both only included one small historical case-control
study.215 This single case-control study compared 30 patients undergoing extensive
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mesenteric excision with a surgical recurrence rate of 2.9% at 5 years to a historical control
group of 34 patients who had a 5-year recurrence rate of 40%.215 Several ongoing trials
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address the possible benefit of a wide mesenteric excision in the context of CD. Such an
excision cannot currently be recommended in routine care.
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We suggest a temporary stoma formation in patients with CD if they are not

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sufficiently optimized for surgery [EL4]

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The decision to create a stoma [primary anastomosis and protective stoma or no

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anastomosis and split stoma] in the context of steroid intake relies mostly on clinical grounds
and experience. There are limited data comparing strategies between primary anastomosis
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or secondary anastomosis in patients with CD treated with steroids.216 However, prolonged

[>6 weeks] and high-dose [≥20 mg prednisolone equivalent] steroid use are associated with
postoperative infectious complications, including anastomotic leakage.149,174,217,218

We recommend strictureplasty as an alternative treatment option to resection in
small-bowel CD [EL2]
Location of CD in the ileum, use of biologics before surgery, and non-conventional
strictureplasty [SP] predict early site-specific recurrence after SP.219,220 However, procedure-
specific recurrence rates are available only for some SP techniques.221 The wide range of
recurrence rates after SP [3–25%] reflects the variability of the population case mix and most
importantly of the follow-up length.220 An extended follow-up time [>5 years] is mandatory to
appraise the true outcome of SP.220 Morbidity and postoperative hospital length of stay were

similar for bowel resection and SP.221-223 Overall, the results of SP compare well with the
recurrence rate after bowel resection, while preserving bowel length.
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We suggest segmental colectomy in selected cases of colonic CD [EL4]
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When a single colonic segment is affected, a segmental colectomy may be the
recommended course of action. On the other hand, the involvement of multiple colon
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segments generally indicates [sub]total colectomy. A meta-analysis compared 223 cases of
subtotal or total colectomies with ileorectal anastomosis and 265 cases of segmental
colectomies in CD.224 In this analysis, there were no significant differences in recurrence
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rates, complications, or need for a permanent stoma. However, it is worth noting that
recurrence occurred on average 4.4 years later in patients who underwent a subtotal or total
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colectomy [p < 0.001].

A recent meta-analysis included patients who underwent segmental colectomy [n = 500],
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subtotal colectomy [n = 510], or total proctocolectomy [n = 426]. Complications were more

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frequent after segmental colectomy compared with subtotal colectomy [OR: 2.84; 95% CI:
1.16–6.96] and after proctocolectomy compared with subtotal colectomy [OR: 0.19; 95% CI:
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0.09–0.38].225 This indicates that subtotal colectomy is generally considered a safer

procedure, although segmental colectomy resulted in fewer patients requiring permanent
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stoma [OR: 0.52; 95% CI: 0.35–0.77]. Subtotal colectomy had higher rates of CD recurrence
[OR: 3.53; 95% CI: 2.45–5.10] and need for repeat surgery [OR: 3.52; 95% CI: 2.27–5.44]
than total proctocolectomy. However, no significant difference in recurrence was observed
between segmental and subtotal colectomy. In rare situations where two distinct colon
segments are affected, it may be worth considering two segmental resections as an
alternative to subtotal colectomy, particularly for patients who have extensive small-bowel
loss. 11
A recent retrospective analysis that included 55 [sub]total colectomies and 30 segmental
colonic resections indicated a trend towards increased postoperative complications after
segmental colectomy [Clavien-Dindo grade ≥ III] of 13.3% versus 7.3% after [sub]total
colectomy. Additionally, there was a trend toward higher rates of hospital readmissions
[13.3% vs 1.8%] and reinterventions [13.3% vs 3.6%] after segmental resection compared
with [sub]total colectomy.226 Another recent multicentre retrospective study including 687
patients concluded that segmental resection was a safe option compared with total
colectomy with the additional benefit of reducing ostomy formation without increasing the risk

of surgical recurrence, particularly in the era of biologics.227 However, the heterogeneity of
the included patients was a limitation of this analysis.
A further retrospective, single-centre study included 200 patients who underwent segmental
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colectomy. A surgical recurrence rate of 31% was observed. Risk factors of recurrence and
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subsequent [sub]total colectomy in multivariate analysis were the presence of three or more
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affected sites [HR: 2.47; 95% CI: 1.22–5.00; p = 0.018] and presence of perianal disease
[HR: 3.23; 95% CI: 1.29–8.07; p = 0.006].228
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In summary, the extent of colonic resection is determined by the clinical presentation
[elective vs emergency surgery] and by the number of colonic segments involved
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[unisegmental vs pancolitis]. Segmental colectomy is generally favoured whenever feasible
as this does not increase the risk of recurrence, particularly in the modern era of biologics
and when other risk factors for recurrence [such as number of affected locations and
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presence of perianal disease] are absent.

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We suggest proctocolectomy as a treatment for CD-associated colorectal cancer or

high-grade dysplasia and segmental colectomy followed by endoscopic surveillance
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in selected cases [EL3]
Patients with chronic inflammation of the large bowel are at an increased risk of
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development of colorectal cancer [CRC], as described in an European Evidence-based

Consensus: IBD and Malignancies.229 Two meta-analyses of cohort studies have clarified the
increased risk of CRC in patients with IBD.230,231 The pooled standardized incidence ratio
[SIR] for CRC was 1.7 [95% CI: 1.2–2.2] in all patients with IBD and 1.9 in CD [95% CI: 1.4–
2.5]. However, the HR of CRC increased in all age groups [HR: 1.40; 95% CI: 1.27–1.53],
consistent with a recent Scandinavian cohort study.231 There was higher risk with extensive
colitis and younger IBD diagnosis [age <30 years], with a SIR of 6.4 [95% CI: 2.4–17.5] and
7.2 [95% CI: 2.9–17.8], respectively. Cumulative risks of cancer were 1%, 2%, and 5% after
10, 20, and >20 years disease duration, respectively.
These reports indicate that the risk of CRC is increased in patients with IBD, but not to the
extent previously reported and not in all patients.
In a Danish cohort,232 CRC patients with CD had a lower frequency of Duke’s A- and B-stage
tumours [36% vs 42%] and a higher frequency of Duke’s C- [31% vs 27%] and D-stage

tumours [23% vs 21%], whereas the frequency of unknown-stage tumours [10%] resembled
that of non IBD-related CRC. The 5-year adjusted mortality rate ratios for patients with
ulcerative colitis [UC] or CD were increased by 1.14 [95% CI: 1.03–1.27] and 1.26 [95% CI:
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1.07–1.49], respectively, compared with patients without IBD. In contrast, in an Irish
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population-based study, patients with IBD-related CRC were about 7 years younger at
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cancer diagnosis than patients with non-IBD CRC but survived about 3 years longer. Older
age, male sex, smoking, and advanced CRC grade and stage were independently
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associated with shorter survival times. When propensity score matching was used to
analyse outcomes, the survival times of CRC patients with and without IBD were not
significantly different.233 Taken together, these results reveal that patients with IBD tend to
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develop CRC at younger ages than patients without IBD. However, no effect of IBD on
patient survival has been consistently demonstrated.
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The risk of CRC in CD increases with longer disease duration, extent of colitis, a familial
history of CRC, coexistent primary sclerosing cholangitis, and the degree and duration of
inflammation. CRC in CD tends to have higher histological grade and more often
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mucinous/signet-ring histological characteristics.11,229,234-236

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The previous ECCO-ESCP Consensus on Surgery for CD11 recommended proctocolectomy

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in fit patients with preoperative diagnosis of cancer or high-grade dysplasia due to the
multifocal nature of dysplasia in CD colitis and the reported high rate of metachronous colon
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cancer after segmental surgical resection.237,238 However, caution is required when

comparing cancer incidence between patients with CD undergoing regular colonoscopies
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and the general population offered cancer screening; lead time bias may overestimate a
possible causal association. Furthermore, the onset of CD is often unclear, while many
cancers are diagnosed concomitantly or immediately after a diagnosis of CD and thus have
a debatable association with CD. Indeed, the incidence of metachronous CRC after
segmental resection is much lower than initially thought239-241 and the prior reported high rate
of metachronous cancer may be attributed to inadequate surgery or even underestimation of
synchronous tumours. Furthermore, most of the available data originate from the early
1970s, when both endoscopic and therapeutic interventions were very different from current
standards.
Therefore, segmental resections and endoscopic surveillance may be proposed in selected
patients after proper consent or in patients who are at high risk for surgery.
Importantly, patients with CRC in CD should be operated according to the principles of
oncological surgery, including adequate lymphadenectomy.242,243 The same principles of
oncological surgery should be considered in the presence of a colonic stenosis and long-
lasting extensive CD colitis can easily be missed upon endoscopic biopsy. Strictureplasty is

not recommended in this context.11,237
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We suggest a defunctioning stoma for non-acute refractory CD colitis to delay or
avoid the need for colectomy [EL5]
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The following two options may be discussed in the presence of refractory CD colitis: a
[sub]total colectomy, particularly as a potentially life-saving procedure in fulminant colitis,
and a defunctioning ileostomy to divert the faecal stream and allow for remission, together
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with intensified medical therapy 244. A diverting ileostomy may delay further procedures,
facilitate perioperative optimization, and allow for a limited resection if required at a later
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stage [i.e. segmental colectomy]. The clinical scenario in which a diverting stoma is
performed to aid the management of extensive perineal disease is covered elsewhere and is
not the focus of the present statement.
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The literature preceding the biologic era reported initial remission rates of up to 90%245-248
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following creation of a defunctioning stoma, which is more than the 50–80% reported in more
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recent series.249,250 Lasting restoration of bowel continuity/stoma reversal was effective in up

to two-thirds of patients but was much lower when perianal disease was also present [i.e.
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29–42%.]6,7 Surgical complications of defunctioning stoma creation were in the expected

range of 3–10% for stoma prolapse/hernia and <5% for renal failure due to high-output
stoma.250 Further bowel resection was reported in up to half of the patients in recent
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series.249,250 Risk factors for proctocolectomy were severe refractory perianal disease,
requirement for combined medical therapy, and a history of more than one biologic drug. For
these patients, early colectomy and end ileostomy [as opposed to a defunctioning ileostomy]
may be discussed.
The following factors should be taken into account when a proctocolectomy is required and
ileal pouch anal anastomosis is considered. In general, more patients have postoperative
pelvic sepsis and a higher pouch failure rate when compared with patients with IPAA for UC.
Patients also have more bowel movements and daytime incontinence when compared with
patients with IPAA for UC. It is worth noting that in selected patients with isolated CD colitis
without small-bowel or perianal involvement, outcomes similar to patients with IPAA for UC
can be obtained [no difference in pelvic sepsis, stool frequency, incontinence, score on
quality-of-life surveys, or pouch failure].251-256

We recommend CD surgery is performed in high-volume IBD centres [EL3]
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The data and appreciation of the benefit of centralization of IBD surgery in high-volume
centres is controversial. Nationwide studies suggested lower mortality in high-volume
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centres, although patients who are frailer and sicker are over-represented in these
centres.257,258 The definition of a high-volume, expert centre and of referral criteria are
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particularly controversial. ECCO has defined quality-of-care criteria and standards for the
care of IBD patients, including patient volume, in a position paper.259
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Practice points
When surgery becomes necessary, it is important to thoroughly assess the bowel, ideally
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preoperatively with MRI enterography. MRI enterography may reveal a distinction between
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inflammatory strictures [amenable to intensified medical therapy] and fibrotic strictures.

Systematically assessing the bowel during surgery may identify further strictures. To
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maximize bowel preservation, the IBD surgeon should be familiar with the different kinds of
strictureplasties, including non-conventional strictureplasties. Nonetheless, strictureplasty of
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the colon is not recommended.260

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The anastomotic technique of choice is not firmly established, although a stapled side-to-
side anastomosis is suggested in small-bowel or ileocolic resections. While segmental
colectomy is advisable when a single colon segment is involved, an oncologic
proctocolectomy is recommended when colonic dysplasia or a neoplasia is identified.
4.2 Postoperative management

We recommend endoscopic surveillance within 6–12 months after surgical resection
in CD [EL2]

A systematic review that included one unblinded RCT and four retrospective cohort studies
revealed a lower recurrence rate in the endoscopy-based management group than in the
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control group.261 Similarly, another systematic review concluded that mucosal changes can
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be observed in up to 73% of cases within 1 year after surgical resection when patients
undergo endoscopic monitoring.262
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In a study that randomized 174 patients in a 2:1 ratio, some underwent colonoscopy at 6
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months with active therapy while others did not undergo colonoscopy and received standard
care. At the 18-month timepoint, clinical recurrence was lower [37.7% vs 46.1%; RR 0.82;
95% CI: 0.56–1.18] in the colonoscopy group and endoscopic recurrence was higher in the
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group that received standard care compared with those under active surveillance [67% vs
49%; p = 0.03].263
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Another systematic review that included 26 prospective studies reported the presence of
mucosal lesions in up to 70% of cases with a median endoscopic follow-up of 12 months.
Notably, more than 50% of these lesions were located at the anastomotic site. Interestingly,
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despite receiving medical treatment, 41% of patients exhibited significant lesions.264 These
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findings are consistent with similar results presented by other studies.265,266 Endoscopic
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monitoring within 6–12 months following surgical resection allows for identification of patients
who may experience disease recurrence, even with ongoing medical therapy, enabling
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proactive intervention.
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We suggest postoperative prophylactic medical therapy after ileocolic resection in
patients with CD at high risk of recurrence [EL3]
Prophylaxis for postoperative recurrence is recommended in patients at high risk for

recurrence. Thiopurines appear to be more effective than placebo in preventing
postoperative recurrence according to different studies.267 Infliximab was more effective than
placebo in preventing endoscopic, but not clinical, recurrence in the prospective PREVENT
268
trial. Overall, anti-TNF agents are the most effective therapy in preventing postoperative
endoscopic recurrence.269 More recent evidence from observational studies described the
efficacy of biologics with different mechanisms of action [ustekinumab and VDZ] in
prevention of recurrence.270 A prospective study presented in abstract form demonstrated
that VDZ was more efficacious than placebo in preventing endoscopic recurrence. Patients
treated with VDZ had a 77.8% chance of having a lower Rutgeerts’ score than patients with

placebo 6 months after an ileocolic resection [p < 0.0001].271 A retrospective multicentre
study from Spain analysed postoperative recurrence rates in 40 patients treated with
ustekinumab and 25 treated with VDZ [all had previous exposure to anti-TNF]. The
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cumulative probability of clinical postoperative recurrence at 12 months after surgery was
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32% and 30% for ustekinumab and VDZ, respectively. The rate of endoscopic recurrence
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was 42% for ustekinumab and 40% for VDZ.272 High-risk patients include those that smoke,
have penetrating disease, or present with an IASC, fistula, or both.273,274
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We recommend extended thromboembolism prophylaxis following hospital discharge
after CD surgery [EL2]
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Although thromboprophylaxis is well documented in patients who have surgery after CRC,
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there is limited evidence in IBD. A recent systematic review suggested that postoperative
DVT risk was similar in IBD to that of patients with advanced CRC. The risk was highest in
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those who had a subtotal colectomy or a proctectomy. The dosage of low molecular weight
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heparin was also assessed in a single-centre study, suggesting that a dose of 4000 IU/day
of low molecular weight heparin was insufficient for IBD patients.275 A minimal duration of
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thromboprophylaxis of 2 weeks postoperatively was suggested.276

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5. Conclusion
There are many options and crossroads in decision making for surgery in CD. Some
approaches have been tested over time and were described in these surgical guidelines.
Although sufficient training, technical expertise, and an adequate caseload to achieve and
maintain subspecialization in IBD surgery are important, the key to success in managing CD
is a multidisciplinary team, as no specialist alone can solve the CD equation. The present
guidelines have been written with this interdisciplinary approach in mind and summarize the
currently available knowledge. The degree of certainty in some aspects of surgery for CD is
closer to eminence than evidence, thus paving the way for further research and better
answers. Consideration of patient lifestyle preference is integral to shared decision making
and key to achieve best standard of care. Revealing gaps in evidence is the first step, as
research focused on clinical needs and gaps in the current evidence will inform guideline

updates. Meanwhile, dynamic integration of gains in knowledge into the ECCO e-Guide will
allow for rapid dissemination. Guidelines provide guidance to the clinician, who adapt expert
knowledge, generic evidence and patient lifestyle preference to individualize care. It is hoped
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that the present work will contribute to optimizing care for patients with CD.
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Funding
This project was initiated, funded, and supported by the ECCO.
Acknowledgements

We gratefully thank Dr Paul Freudenberger for the literature search and full-text retrieval;
Torsten Karge for support on informatics and on the web Guidelines platform; and the ECCO
Office for logistical and coordination support.
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We gratefully thank the EFCCA patient representatives Bastien Corsat, Xavier Donnet,
Evelyn Gross, Antonio Valdivia, Janek Kapper, and Lucie Lastikova who proactively
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collaborated in the development of these Guidelines.
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We thank Ibrahim Ethem Gecim for his work in the abstract screening process.
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We would like to thank and acknowledge the ECCO National Representatives and additional
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reviewers, who acted as external reviewers and provided suggestions on the

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recommendations and supporting text to this document: Pascal Juillerat, Allesandra Soriano,
Mark Samaan, Tiago Cúrdia Gonçalves, Edoardo Savarino, Federica Furfaro, Davide
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Giuseppe Ribaldone, Gulustan Babayeva-Sadiqova, Aurelien Amiot, Gianmichele Meucci,

Iago Rodríguez Lago, Mathieu Uzzan, Gerassimos Mantzaris, Beatriz Gros Alcalde, Vito
ce
Annese, Eduard Brunet Mas, Maria Jose Garcia, Eirini Zach, John Marshall, Carla Felice,
Maha Maher, Paul Pollack, Andreas Blesl, Negreanu Lucian, Ferdinando D'Amico, Dimitrios
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Karagiannis, Patrick Allen, Oliver Bachmann, Imerio Angriman, Anna Kagramanova,

Dahham Alsoud, Natália Queiroz, Usha Chauhan, Petra Golovics, Chen Sarbagili, Lorenzo
Bertani, Ulf Helwig, Clas-Göran af Björkesten, Ante Bogut, Anthony Buisson, Ignacio
Catalan-Serra, Aslı Çifcibaşı Örmeci, Marco Daperno, Mihai Mircea Diculescu, Dana
Duricová, Piotr Eder, Magdalena Gawron-Kiszka, Ayal Hirsch, Ondrej Hradsky, Hendrik
Laja, Sara Onali, Samuel Raimundo Fernandes, Christian Philipp Selinger, Helena Tavares
de Sousa, Svetlana Turcan, Sophie Vieujean, and Yamile Zabana.
Authors’ contribution
Michel Adamina, Pär Myrelid, Hannah Gordon, and Tim Raine coordinated the project; Silvia
Minozzi provided expert methodology advice, trained the working group members, and
performed the analysis of data; Uri Kopylov, Bram Verstockt, Maria Chaparro, Christianne
Buskens, and Janindra Warusavitarne coordinated the working groups; all the Authors listed

contributed to the identification of relevant data, data interpretation, and drafted and
discussed the final recommendations; all Authors participated in the final Consensus; Michel
Adamina and Pär Myrelid drafted this manuscript.
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Conflict of interests
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ECCO has diligently maintained a disclosure policy of potential conflicts of interest [CoI]. The
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conflict-of-interest declaration is based on a form used by the International Committee of
Medical Journal Editors [ICMJE]. The CoI statement is not only stored at the ECCO Office
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and the editorial office of JCC but is also open to public scrutiny on the ECCO website
[https://www.ecco-ibd.eu/about-ecco/ecco-disclosures.html], providing a comprehensive
overview of potential conflicts of interest of authors.
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Disclaimer
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The ECCO Guidelines are targeted at health care professionals only and are based on an
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international consensus process.

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This process includes intensive literature research as explained in the methodology section
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and may not reflect subsequent scientific developments, if any, until the next Guidelines
update is prepared. Readers of the Guidelines acknowledge that research about medical
and health issues is constantly evolving and diagnoses, treatments, and dose schedules for
medications are being revised continually. Therefore, the European Crohn´s and Colitis
Organisation (ECCO) encourages all readers to also consult the most up-to-date published
product information and data sheets provided by the manufacturers as well as the most
recent codes of conduct and safety regulations.
Any treatment decisions are to be made at the sole discretion and within the exclusive
responsibility of the individual clinician and should not be based exclusively on the content of
the ECCO Guidelines. The European Crohn´s and Colitis Organisation (ECCO) and/or any
of its staff members and/or any consensus contributor may not be held liable for any
information published in good faith in the ECCO Consensus Guidelines. ECCO makes no
representations or warranties, express or implied, as to the accuracy or completeness of the
whole or any part of the Guidelines. ECCO does not accept, and expressly disclaims,
responsibility for any liability, loss or risk that may be claimed or incurred as a consequence

of the use or application of the whole or any part of the Guidelines.
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When the Guidelines mention trade names, commercial products or organizations, this does
not constitute any endorsement by ECCO and/or any consensus contributor.
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t
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e d
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Figures
Figure 1. Classification of perianal fistulising Crohn’s disease
At any moment throughout its disease course, perianal fistulising Crohn’s disease can be

classified into one of four classes134
(reprinted with permission from Elsevier, License Number 5760781248280).
t
ip
cr
Class 2a: repair
us
Symptomatic fistulae suitable
for combined medical and Class 2c-i: early and Class 3: severe disease Class 4a: repair
surgical closure or repair rapidly progressive with exhausted Symptomatic sinuses
(including seton removal) disease perineum and or wounds suitable
and patient goal is fistula Early and rapidly adverse features for combined medical
Class 1: minimal disease
progressive disease Severely symptomatic and
Minimal symptoms and
an
destructive to the disease (despite patient goal
anorectal disease burden,
perineum or to quality defunctioning),
requiring minimal
Class 2: chronic of life (or both), such with irreversible
intervention over time
symptomatic that early intervention perineal
fistulae destruction, or
These patients will align
Perianal fistulising Defunctioni Proctecto Class 4: perineal
M
with one of three groups,

Crohn's disease ng my symptoms after
according to their goals, as
proctectomy
well as their symptoms
and impact on quality of Class 2c-ii: gradually Class 4b: symptom
debilitating disease control Chronic
Gradually debilitating symptoms related to
d
symptomatic fistulae sinuses or wounds that

Class 2b: symptom unsuitable for surgical affect quality of life
control Chronic repair, and that are
e
symptoms related to which cause severe

fistulae (pain and symptoms, limiting or patient goal
discharge) that affect quality of life so is symptom control
pt
quality of life. Fistulae are markedly that

currently unsuitable for
ce
Ac
Figure 2. Treatment algorithm for Class 2A CD fistulae aiming for repair.
Perianal fistula abscess

Seton drainage I&D + antibiotics
t
Start anti-TNF
ip
cr
No proctitis Proctitis
Single internal
opening us
Multiple internal
openings
an
Superficial Transsphincteric
M
[intersphincteric] tract
tract
e d
Fistulotomy Surgical closure Stem cells Seton removal

under anti-TNF under medical
pt
treatment
[AF or LIFT]
ce
Ac
Fistula recurrence
Class 2a [repair]: Class 2b [symptom control]
- Consider approach outside - Medical treatment

guideline *VAAFT/OVESCO+
- Chronic seton
- Experimental therapies

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Manuscript Doi: 10.

Michel Adamina1,2, Silvia Minozzi, Janindra Warusavitarne, Christianne Buskens, Maria

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Medicine, University of Fribourg, Fribourg, Switzerland

Johanna Buskens Netherlands

Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid

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Chair of Internal Medicine, Faculty of Medicine, University of Ljubljana,

João Guedelha Department of Gastroenterology and Hepatology, University Hospitals Leuven,

Javier P. Gisbert Gastroenterology Department. Hospital Universitario de La Princesa, Instituto de

Gionata Fiorino IBD Unit, San Camillo-Forlanini Hospital, Rome, Italy

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Linköping University, Linköping, Sweden

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Keywords: Crohn’s disease; Surgery; Inflammatory bowel disease (IBD)

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A detailed description of the methodology used is presented in the supplementary materials.

3.1. Medical approaches

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We do not recommend use of antibiotics as monotherapy for treatment of complex

Statement 3.2 ECCO CD Treatment GL [2024]

We suggest against using thiopurines as monotherapy [azathioprine, mercaptopurine]

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We suggest use of adalimumab for induction and maintenance of remission in

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maintained response at 12 months [41% remission, 8% partial response].44 Additional data

levels, suggesting the need for personalized dosing in this setting.35,37,40,45

Statement 3.5 ECCO CD Treatment GL [2024]

There is insufficient evidence to recommend use of certolizumab pegol as a treatment

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There is insufficient evidence to recommend use of vedolizumab for the treatment of

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a design specifically evaluating VDZ for fistula closure.

There is insufficient evidence to recommend use of ustekinumab as a treatment for

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responders to induction with ustekinumab who were re-randomized to receive ustekinumab

higher proportion of fistula healing in patients treated with ustekinumab, no significant

Statement 3.8 ECCO CD Treatment GL [2024]

There is insufficient evidence to recommend use of upadacitinib for the treatment of

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including small sample size and inadequate statistical power.

There is lack of evidence to recommend use of risankizumab for the treatment of

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undergoing fistulotomy when compared with sphincter-preserving procedures, seton

of 3–13% up to 1 year post-fistulotomy55,57,58,60 were reported. However, few studies provide

Statement 3.11 ECCO CD Treatment GL [2024]

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postoperative higher incontinence rate of up to 20% following AF. Conversely, one

Statement 3.12 ECCO CD Treatment GL [2024]

We recommend ligation of the intersphincteric fistula tract as a treatment option for

selected patients with CD and complex perianal fistulae [EL3]

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predominantly wound dehiscence. Incontinence rates appeared to be lower when compared

incontinence in 37 patients demonstrated increased incontinence in 16% of patients after

Statement 3.13 ECCO CD Treatment GL [2024]

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perianal CD fistulae (EL4)

A systematic review of 12 observational studies including 84 patients with CD demonstrated

Statement 3.15 ECCO CD Treatment GL [2024]