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Adler J, Gadepalli S, Rahman M, Kim S. Early tumour necrosis factor antagonist treatment prevents perianal fistula development in children with Crohn's disease: post hoc analysis of the RISK study. Gut 2025; 74:539-546. [PMID: 39667905 DOI: 10.1136/gutjnl-2024-333280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 11/24/2024] [Indexed: 12/14/2024]
Abstract
BACKGROUND One in three children with Crohn's disease develop perianal fistula complications (PFCs), among the most disturbing and difficult-to-treat disease-related complications. Retrospective evidence suggests PFCs may be preventable. OBJECTIVE We aimed to determine if early antitumour necrosis factor-alpha (anti-TNF⍺) therapy prevents PFC development in a well-characterised prospective cohort of paediatric patients with Crohn's disease who were free from PFC at enrolment. DESIGN RISK was a multicentre inception cohort of children newly diagnosed with Crohn's disease. We included all patients who had never experienced PFCs 30 days after study enrolment. We conducted nearest-neighbour propensity score-matched triad analyses. Matching was performed to balance patient characteristics across three mutually exclusive treatment groups based on therapy prior to either PFC development or the end of the observation period. RESULTS Among 873 patients without perianal fistula, 447 matched patients were included (149 per treatment group). The presence of non-penetrating perianal lesions (large skin tags, ulcers and/or fissures) was significantly associated with PFC development, with 4-fold greater odds of PFC (OR 4.08, 95% CI (95% CI) 1.70 to 9.78; p=0.0016). Early anti-TNF⍺ therapy was associated with an 82% decrease in the odds of PFC (OR 0.18, 95% CI 0.05 to 0.66; p=0.01). Among those with perianal lesions, anti-TNF⍺ therapy was associated with 94% reduced odds of PFC development (OR 0.055, 95% CI 0.006 to 0.50; p=0.010). No other treatment group was associated with reduced risk of PFC. CONCLUSION Early anti-TNF therapy prevents perianal fistula development, especially among patients at increased risk.
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Affiliation(s)
- Jeremy Adler
- Pediatric Gastroenterology, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA
- Susan B. Meister Child Health Evaluation and Research Center, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Samir Gadepalli
- Susan B. Meister Child Health Evaluation and Research Center, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA
- Pediatric Surgery, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Moshiur Rahman
- Susan B. Meister Child Health Evaluation and Research Center, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Sandra Kim
- Pediatric Gastroenterology, Cleveland Clinic, Cleveland, Ohio, USA
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Takano S, Nakamura Y, Tamaoka K, Yoshimoto T, Irei Y, Tsuji Y. Management of Anal Fistula with Crohn's Disease. J Anus Rectum Colon 2025; 9:10-19. [PMID: 39882221 PMCID: PMC11772789 DOI: 10.23922/jarc.2024-067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 07/31/2024] [Indexed: 01/31/2025] Open
Abstract
Crohn's disease (CD) causes gastrointestinal symptoms (i.e., diarrhea and abdominal pain), systemic symptoms (i.e., fatigue, anemia, weight loss, and fever), and perianal fistulas that produce anal pain. Because of the frequent occurrence of diarrhea and ulcers in the rectum, CD is often exacerbated by perianal abscesses and/or fistulas. Perianal fistulizing CD (PFCD) has an unknown etiology and recurring symptoms such as pain and discharge, which seriously affects the patient's quality of life (QOL). In the past, radical surgery was performed for PFCD, but due to the risk of anal sphincter impairment, conservative therapy using antibiotics and immunosuppressive medications is currently the first treatment option. PFCD management has greatly improved with the use of biologics such as the antitumor necrosis factor alpha (TNF-α) antibodies infliximab and adalimumab. In this review, the results of the administration of anti-TNF-α (certolizumab pegol), anti-interleukin-12/23 (ustekinumab), and anti-α4β7 integrin antibodies (vedolizumab) were evaluated. Our investigation showed that these medications may be effective for maintenance therapy to prevent the recurrence of anal fistulas. In addition to biologics, molecular target drugs and even regenerative medicine using mesenchymal stem cells have been introduced to further expand the treatment options for consideration by medical personnel. We herein discuss the management of PFCD by focusing on studies conducted in the United States and Europe where researchers used recommended guidelines and consensus statements to evaluate the efficacy of each medication and published their findings in peer-reviewed journals.
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Affiliation(s)
- Shota Takano
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Yasushi Nakamura
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Kohei Tamaoka
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Takafumi Yoshimoto
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Yasue Irei
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Yoriyuki Tsuji
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
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McNamara J, Wilson W, Pipicella JL, Ghaly S, Begun J, Lawrance IC, Gearry R, Andrews JM, Connor SJ. Epidemiology and Treatment Patterns of Fistulizing Crohn's Disease in a Large, Real-World Australasian Cohort. GASTRO HEP ADVANCES 2024; 4:100594. [PMID: 39996242 PMCID: PMC11849075 DOI: 10.1016/j.gastha.2024.100594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 11/23/2024] [Indexed: 02/26/2025]
Abstract
Background and Aims Fistulizing Crohn's Disease (fCD) affects up to 50% of people with Crohn's Disease over their lifetime. Despite this high prevalence, the burden of disease, treatment and natural history in the current biologic era are poorly described. This study explores demographic, disease and treatment factors in a real-world Australasian cohort. Methods A large real-world cohort of people with inflammatory bowel disease under routine care was interrogated in August 2023. Current fCD was defined as fistula(e) on most recent clinical, radiologic or endoscopic investigation; prior fCD was defined as the resolution of fistula(e) on most recent documentation. Results Of 3075 people with Crohn's Disease, 7.4% had current and 10.1% prior fCD (n = 224 & 311). Most patients were in Australia (77%), where 19.3% had current or previous fCD compared to 11% in New Zealand (P < .001). Patients with current or previous fCD were younger compared to those without (P = .003 & P < .001). Males were more commonly affected (P = .021). Current or prior fCD were more likely to be on biologic therapy (P < .001), with anti-tumor necrosis factor agents most frequently utilized. Conversely, those without fCD were more likely on Ustekinumab or Vedolizumab compared to current and prior fCD groups. People with fistulizing disease had higher hospitalization rates, while the prior fCD cohort had longer hospital admissions and more frequently required surgical intervention. Conclusion People with fCD used more health-care resources, making this an important area for further research into care gaps to improve outcomes and optimal treatment approaches.
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Affiliation(s)
- Jack McNamara
- Liverpool Hospital Department of Gastroenterology & Hepatology, Sydney, NSW, Australia
- Ingham Institute for Applied Medical Research, Gastroenterology, Hepatology and Inflammatory Bowel Disease Research Group, Liverpool, NSW, Australia
| | | | - Joseph L. Pipicella
- Ingham Institute for Applied Medical Research, Gastroenterology, Hepatology and Inflammatory Bowel Disease Research Group, Liverpool, NSW, Australia
- Crohn’s Colitis Cure, Sydney, NSW, Australia
- Medicine & Health (South Western Sydney Clinical School), University of New South Wales, Sydney, NSW, Australia
| | - Simon Ghaly
- Department of Gastroenterology, St Vincent’s Hospital, Sydney, NSW, Australia
- St Vincent’s Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Jakob Begun
- Department of Gastroenterology, Mater Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, St Lucia, QLD, Australia
| | - Ian C. Lawrance
- Crohn’s Colitis Cure, Sydney, NSW, Australia
- School of Medicine, University of Western Australia, Crawley, WA, Australia
| | - Richard Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Jane M. Andrews
- Crohn’s Colitis Cure, Sydney, NSW, Australia
- Central Adelaide Local Health Network, Adelaide, SA, Australia
- University of Adelaide Faculty of Health Sciences, Adelaide, SA, Australia
| | - Susan J. Connor
- Liverpool Hospital Department of Gastroenterology & Hepatology, Sydney, NSW, Australia
- Ingham Institute for Applied Medical Research, Gastroenterology, Hepatology and Inflammatory Bowel Disease Research Group, Liverpool, NSW, Australia
- Crohn’s Colitis Cure, Sydney, NSW, Australia
- Medicine & Health (South Western Sydney Clinical School), University of New South Wales, Sydney, NSW, Australia
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Singh JP, Aleissa M, Drelichman ER, Mittal VK, Bhullar JS. Navigating the complexities of perianal Crohn's disease: Diagnostic strategies, treatment approaches, and future perspectives. World J Gastroenterol 2024; 30:4745-4753. [PMID: 39610776 PMCID: PMC11580605 DOI: 10.3748/wjg.v30.i44.4745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/25/2024] [Accepted: 10/24/2024] [Indexed: 11/12/2024] Open
Abstract
This article discusses the literature review article by Pacheco et al published in July 2024; the authors provided good reviews of perianal Crohn's disease (CD), and challenges faced by clinicians in the management. CD, characterized by its chronic and relapsing nature, is an idiopathic condition that can involve any segment of the gastrointestinal tract. Perianal disease impacts up to 40% of patients with CD, with perianal fistulas constituting up to 80% of perianal lesions. Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients. The management focuses on controlling the perianal sepsis and treating luminal CD. Biologics are crucial to the treatment approach, and results have been encouraging. The surgery focuses on controlling the sepsis, with more definitive treatments being fistula surgery, fecal diversion, and proctectomy as the last resort. This manuscript briefly describes the burden of CD, the challenges posed by perianal CD, and the role of different treatment modalities from colorectal surgeon's perspective.
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Affiliation(s)
- Jai P Singh
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Southfield, MI 48075, United States
| | - Maryam Aleissa
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Ernesto R Drelichman
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Vijay K Mittal
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Jasneet S Bhullar
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
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Colombel JF, Lacerda AP, Irving PM, Panaccione R, Reinisch W, Rieder F, Steinlauf A, Schwartz D, Feng T, Dubcenco E, Anyanwu SI, Laroux FS, Cunneen C, Powell N. Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn's Disease: A Post Hoc Analysis of 3 Phase 3 Trials. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00860-7. [PMID: 39326583 DOI: 10.1016/j.cgh.2024.08.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/06/2024] [Accepted: 08/09/2024] [Indexed: 09/28/2024]
Abstract
BACKGROUND & AIMS Efficacy of upadacitinib, an oral Janus kinase inhibitor, for moderate-to-severe Crohn's disease was demonstrated in phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials; this post hoc analysis evaluated upadacitinib outcomes in patients with fistulizing disease in these studies. METHODS Patients were randomized (2:1) to once daily upadacitinib 45 mg or placebo for 12 weeks. Upadacitinib 45 mg clinical responders were rerandomized (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks. In patients with fistulas (any and perianal), resolution of drainage, closure of external openings, clinical remission, endoscopic response, and safety were assessed. RESULTS Of 1021 patients in U-EXCEL and U-EXCEED, 143 (14.0%) had any fistulas at baseline (66 draining); of these, most (n = 128) had perianal fistulas (56 draining). Greater proportions of patients receiving upadacitinib vs placebo achieved resolution of drainage of perianal fistulas at the end of induction (placebo: 5.6%, n/n = 1/18; upadacitinib 45 mg: 44.7%, n/n = 17/38; P = .003) and maintenance (placebo: 0%, n/n = 0/11; upadacitinib 15 mg: 28.6%, n/n = 4/14; P = .105; upadacitinib 30 mg: 23.1%, n/n = 3/13; P = .223) and closure of perianal fistula external openings (for induction, placebo: 4.8%, n/n = 2/42; upadacitinib 45 mg: 22.1%, n/n = 19/86; P = .013; for maintenance, placebo: 0%, n/n = 0/30; upadacitinib 15 mg: 18.8%, n/n = 6/32; P = .024; upadacitinib 30 mg: 16.0%, n/n = 4/25; P = .037). CONCLUSION Patients with fistulizing disease (primarily perianal) treated with upadacitinib achieved higher rates of resolution of drainage, closure of external openings, clinical remission, and endoscopic response vs placebo. CLINICALTRIALS gov, Numbers: NCT03345849 (U-EXCEL), NCT03345836 (U-EXCEED), NCT03345823 (U-ENDURE).
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Affiliation(s)
- Jean-Frédéric Colombel
- Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
| | | | - Peter M Irving
- IBD Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Remo Panaccione
- Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Walter Reinisch
- Department of Internal Medicine, Medical University of Vienna, Vienna, Austria
| | - Florian Rieder
- Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, Ohio
| | - Adam Steinlauf
- Department of Gastroenterology, Mount Sinai Hospital, New York, New York
| | - David Schwartz
- Department of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Tian Feng
- AbbVie Inc., North Chicago, Illinois
| | | | | | | | | | - Nick Powell
- Division of Digestive Diseases, Imperial College London, London, United Kingdom
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Gadepalli SK, Adler J. Perianal disease: Updates and controversies in closing the gaps. Semin Pediatr Surg 2024; 33:151402. [PMID: 38603820 DOI: 10.1016/j.sempedsurg.2024.151402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/13/2024]
Abstract
Perianal complications are common and morbid in children with Crohn's disease. In this review, we describe the epidemiology, the presentation and diagnosis, evaluation and management. We focus on updates such as the increasing frequency of biologic medications and MRI for evaluation. We also highlight controversies on the timing and approaches to surgical techniques. Finally, perianal disease requires the coordination of multidisciplinary care with nursing, radiology, gastroenterology, and surgery to optimize outcomes - both medical and patient-centered.
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Affiliation(s)
- Samir K Gadepalli
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, United States; Susan G. Meister CHEAR Center, University of Michigan, Ann Arbor, MI, United States.
| | - Jeremy Adler
- Susan G. Meister CHEAR Center, University of Michigan, Ann Arbor, MI, United States; Division of Pediatric Gastroenterology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
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Irani M, Abraham B. Choosing Therapy for Moderate to Severe Crohn's Disease. J Can Assoc Gastroenterol 2024; 7:1-8. [PMID: 38314180 PMCID: PMC10836982 DOI: 10.1093/jcag/gwad023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2024] Open
Abstract
The availability of approved therapies for Crohn's disease has significantly increased over the past decade. To choose the appropriate therapy for the patient, ideally head to head studies, and data on positioning could help the provider individualize the decision. Due to the paucity of head-to-head trial data, we turn to network meta-analysis and real-world studies to help guide our treatment choices. Ultimately, the best approach is to consider each patient on an individual basis, taking into consideration the characteristics of their disease, individual risk factors, extra-intestinal manifestations, co-morbid conditions, patient age, cost, and personal preferences. In this review, we summarize the evidence comparing biologic as well as small molecule therapies for the treatment of moderate-to-severe Crohn's disease. We have summarized the evidence in relation to factors such as efficacy, fistulizing disease, pregnancy, infection risk, and co-existing conditions.
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Affiliation(s)
- Malcolm Irani
- Division of Gastroenterology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, 6550 Fannin Street, Smith 1201, Houston, TX 77030, USA
| | - Bincy Abraham
- Division of Gastroenterology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, 6550 Fannin Street, Smith 1201, Houston, TX 77030, USA
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Rosevics L, Savio MC, Lima Júnior E, Ramos Júnior O. FISTULIZING PERIANAL CROHN'S DISEASE: IS THE PATIENT'S SEX A BURDEN? A SYSTEMATIC REVIEW. ARQUIVOS DE GASTROENTEROLOGIA 2023; 60:490-524. [PMID: 38018554 DOI: 10.1590/s0004-2803.230402023-28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/31/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome. OBJECTIVE Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients. METHODS This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. RESULTS Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men. CONCLUSION This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.
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Nakase H, Esaki M, Hirai F, Kobayashi T, Matsuoka K, Matsuura M, Naganuma M, Saruta M, Tsuchiya K, Uchino M, Watanabe K, Hisamatsu T. Treatment escalation and de-escalation decisions in Crohn's disease: Delphi consensus recommendations from Japan, 2021. J Gastroenterol 2023; 58:313-345. [PMID: 36773075 PMCID: PMC10050046 DOI: 10.1007/s00535-023-01958-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/08/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn's disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD. METHODS PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021. RESULTS Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD. CONCLUSIONS These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.
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Affiliation(s)
- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-Ku, Sapporo, Hokkaido 060-8543 Japan
| | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611 Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Motoi Uchino
- Division of Inflammatory Bowel Disease, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Hyogo Japan
| | - Kenji Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Hyogo Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611 Japan
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Predictors of Perianal Fistula Healing in Children With Newly Diagnosed Crohn Disease. J Pediatr Gastroenterol Nutr 2022; 75:709-716. [PMID: 36399175 DOI: 10.1097/mpg.0000000000003595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Perianal fistulas are among the most severe complications of Crohn disease, but limited data regarding their outcomes are available in children. Our objective was to determine predictors of perianal fistula healing among pediatric patients newly diagnosed with Crohn disease. METHODS This single-center retrospective study followed patients with perianal fistulas at Crohn disease diagnosis until fistula healing. Time to healing was analyzed using Cox proportional hazard regression models considering relevant covariates including patient demographics, disease characteristics, medical therapies [no anti-tumor necrosis factor (TNF)α therapy, anti-TNFα therapy ±therapeutic drug monitoring], and perianal surgical procedures including fistulotomy, fistulectomy, removal of perianal lesions, seton placement, and incision and drainage. RESULTS Of 485 patients identified, 107 (22%) had a perianal fistula at Crohn disease diagnosis. Multivariate analysis identified that perianal fistulotomy, fistulectomy, and lesion removal [hazard ratio (HR) 0.46; P = 0.028], non-White race (HR 0.30, P < 0.01), and male sex (HR 0.42; P = 0.02) were associated with delayed fistula healing. Faster fistula healing was associated with treatment with anti-TNFα with therapeutic drug monitoring (HR 1.78, P = 0.009). There were no other differences in healing by treatment. CONCLUSIONS Fistulotomy, fistulectomy, and perianal lesion removal as well as non-White race were associated with delayed fistula healing. Anti-TNFα therapy was associated with faster fistula healing when combined with therapeutic drug monitoring, compared to all other medical treatment groups, including anti-TNFα therapy without therapeutic drug monitoring.
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Bouchard D, Pigot F, de Parades V, Staumont G, Abramowitz L, Siproudhis L, Bouchard D, Pigot F, de Parades V, Staumont G, Abramowitz L, Siproudhis L, Tracanelli L, Fathallah N, Babin-Pigot E, Ferry M, Bouguen G, Laharie D, Cotte E, Panis Y, Peyrin-Biroulet L, Roblin X, Zerbib P. Management of perianal fistulas in Crohn’s disease: a 2021 update of the French National Society of Coloproctology consensus. Tech Coloproctol 2022; 26:805-811. [DOI: 10.1007/s10151-022-02678-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 07/29/2022] [Indexed: 11/28/2022]
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Wetwittayakhlang P, Al Khoury A, Hahn GD, Lakatos PL. The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials. J Clin Med 2022; 11:3045. [PMID: 35683433 PMCID: PMC9181669 DOI: 10.3390/jcm11113045] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/21/2022] [Accepted: 05/25/2022] [Indexed: 02/04/2023] Open
Abstract
Fistulizing Crohn's disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30-50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Alex Al Khoury
- Division of Gastroenterology, University of Florida, Jacksonville, FL 32209, USA;
| | - Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Graduate Course Sciences in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- First Department of Medicine, Semmelweis University, 1085 Budapest, Hungary
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Hahn GD, Golovics PA, Wetwittayakhlang P, Al Khoury A, Bessissow T, Lakatos PL. Is There a Best First Line Biological/Small Molecule in IBD: Are We Ready for Sequencing? Biomedicines 2022; 10:749. [PMID: 35453498 PMCID: PMC9026422 DOI: 10.3390/biomedicines10040749] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/19/2022] [Accepted: 03/21/2022] [Indexed: 11/17/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, life-long inflammatory condition of the gastrointestinal tract. Treatment strategy depends on the severity of the disease course. IBD physicians need to be aware of the life-long treatment options available. The goal is not only to achieve clinical remission but to halt or stabilize the chronic inflammation in the intestines to prevent further structural damage. Therefore, the use of early biologic therapy is recommended in moderate-to-severe IBD patients. However, in the last decade, use of therapeutic drug monitoring has increased considerably, opening an opportunity for sequencing. This review summarizes the available evidence on biologic and small molecules therapy in Crohn's disease (CD) and ulcerative colitis (UC) in different clinical scenarios, including perianal CD, the elderly, extra intestinal manifestations, and pregnancy.
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Affiliation(s)
- Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (P.A.G.); (P.W.); (T.B.)
- School of Medicine, Graduate Course Sciences in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil
| | - Petra Anna Golovics
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (P.A.G.); (P.W.); (T.B.)
- Department of Gastroenterology, Hungarian Defence Forces, Medical Centre, H-1062 Budapest, Hungary
| | - Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (P.A.G.); (P.W.); (T.B.)
- Unit of Gastroenterology and Hepatology, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Alex Al Khoury
- Division of Gastroenterology, University of Florida Jacksonville, Jacksonville, FL 32209, USA;
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (P.A.G.); (P.W.); (T.B.)
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada; (P.A.G.); (P.W.); (T.B.)
- 1st Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary
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Deng F, Xia P, Wu Z, Zhou H, Wang X. Perianal and Luminal Relapse Following Perianal Surgical Intervention in Crohn's Disease. Int J Gen Med 2021; 14:3387-3396. [PMID: 34285563 PMCID: PMC8286149 DOI: 10.2147/ijgm.s315505] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/07/2021] [Indexed: 12/02/2022] Open
Abstract
Background and Aims Fistula relapse occurs in 20–30% of patients with perianal Crohn’s disease (PCD) despite optimal medico-surgical management. We aimed in this study to assess the rate of perianal and luminal relapse after surgically induced remission and to determine factors associated with fistula relapse. Methods Consecutive perianal CD patients who achieved clinical remission after surgery for fistulising PCD from January 2013 to January 2019 were included. The cumulative probabilities of relapse-free survival were estimated using the Kaplan–Meier method. Results A total of 130 patients were included. Sixty-six of 130 patients received infliximab (IFX) therapy after perianal surgery. After a median follow-up of 62 months (interquartile range [IQR]: 28–117 months), perianal relapse occurred in 30 of 64 (46.9%) nonbiological medication-treated cases and in 14 of 66 (21.1%) cases in the IFX therapy group. The cumulative probabilities of perianal relapse-free survival in patients with nonbiological treatment were 77.1% at 1 year, 54.6% at 3 years, and 30% at 5 years. The rates of survival without perianal fistula relapse in the IFX-treated group were 91.6%, 69.2%, and 59.3% at 1, 3 and 5 years, respectively. In patients treated with IFX after perianal surgery, discontinuation of IFX therapy (odds ratio [OR]=2.43, p=0.036), a penetrating CD phenotype (OR=4.324, p=0.019), and a complex perianal fistula (OR=3.392, p=0.026) were independently associated with perianal relapse in multivariate analysis. Conclusion Infliximab therapy reduced the risk of perianal relapse after surgical remission in PCD patients compared with nonbiological treatment. However, approximately 40% of patients using infliximab experienced perianal relapse at 5 years, and patients who discontinued use of IFX or experienced a penetrating phenotype or a complex perianal fistula were associated with increased relapse rate.
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Affiliation(s)
- Feihong Deng
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
| | - Pianpian Xia
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
| | - Zengrong Wu
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
| | - Hejun Zhou
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
| | - Xuehong Wang
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.,Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People's Republic of China
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Vasudevan A, Bruining DH, Loftus EV, Faubion W, Ehman EC, Raffals L. Approach to medical therapy in perianal Crohn's disease. World J Gastroenterol 2021; 27:3693-3704. [PMID: 34321838 PMCID: PMC8291021 DOI: 10.3748/wjg.v27.i25.3693] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/13/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Perianal Crohn's disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn's disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn's disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn's disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn's disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.
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Affiliation(s)
- Abhinav Vasudevan
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Edward V Loftus Jr
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - William Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Eric C Ehman
- Department of Radiology, Mayo Clinic, Rochester, MN 55905, United States
| | - Laura Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
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16
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Nam K, Jung WB, Lee SB, Soh JS, Yang SS, Jung SW. Predictors of reoperation for perianal fistula in Crohn's disease. J Dig Dis 2021; 22:334-341. [PMID: 33949127 DOI: 10.1111/1751-2980.12996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 04/29/2021] [Accepted: 05/02/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Treating perianal fistula in cases of Crohn's disease (CD) remains challenging and the postoperative recurrence rate of perianal fistula is 22%-28%. This study aimed to identify the predictive risk factors for reoperation in Korean CD patients with perianal fistula. METHODS Medical records of the patients with clinically and pathologically confirmed CD who underwent surgical treatment for perianal fistulas at four referral centers in Korea between March 2010 and February 2020 were retrospectively reviewed. The rate of reoperation due to perianal fistula recurrence, which was defined as any subsequent surgery for perianal fistula or abscess, and the potential risk factors for reoperation were analyzed. RESULTS Fifty-one patients at a mean age of 22 years were included in the study. During a median follow-up period of 26 months (range 2-89 mo), 21 (41.2%) patients underwent reoperation because of recurrent perianal fistula or abscess. The median interval from the first surgery to reoperation was 13 months. A multivariate Cox regression analysis revealed that drug escalation (from 5-aminosalicylic acid [5-ASA] to thiopurine or from 5-ASA or thiopurine to anti-tumor necrosis factor agents) after the first surgery was associated with a reduced likelihood of reoperation (hazard ratio 0.316, 95% confidence interval 0.117-0.858, P = 0.024). CONCLUSIONS The postoperative recurrence rate was relatively high (41.2%) after the first surgery for perianal fistula in Korean patients with CD. Drug escalation therapy after the first surgery may help reduce the need for reoperation for perianal fistula.
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Affiliation(s)
- Kwangwoo Nam
- Department of Gastroenterology, Dankook University Hospital, Dankook University College of Medicine, Cheonan, South Korea
| | - Won Beom Jung
- Department of Surgery, Haeundae Paik Hospital, College of Medicine, University of Inje, Busan, South Korea
| | - Seung Bum Lee
- Department of Gastroenterology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Jae Seung Soh
- Department of Gastroenterology, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang, South Korea
| | - Song Soo Yang
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Seok Won Jung
- Department of Gastroenterology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
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Lukin DJ. Predictors of Perianal Fistula Relapse in Crohn's Disease. Inflamm Bowel Dis 2020; 26:932-933. [PMID: 31504545 DOI: 10.1093/ibd/izz198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Indexed: 01/02/2023]
Affiliation(s)
- Dana J Lukin
- Jill Roberts Center for Inflammatory Bowel Disease, New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York, USA
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