Intestinal Research

Original Articles

Comparative effectiveness of ustekinumab versus infliximab in the management of perianal fistulizing Crohn's disease: a retrospective study in China: Mengqi Chen, Zihan Chen, Jianming Lin, Linxin Liu, Tong Tu, Xiaoling Li, Baili Chen, Yao He, Minhu Chen, Zhirong Zeng, Xiaojun Zhuang; Received October 16, 2024 Accepted April 23, 2025 Published online June 11, 2025; DOI: https://doi.org/10.5217/ir.2024.00168 [Epub ahead of print]

Abstract PDF: Background/Aims
Ustekinumab (UST) and infliximab (IFX) are both effective in the treatment of perianal fistulizing Crohn’s disease (CD), but limited research has focused on comparing the efficacy of UST versus IFX in this field. This study aimed to compare the effectiveness of UST or IFX in treating perianal fistula of CD patients naive to biological agents in a real-world setting.
Methods
A retrospective cohort study included patients with perianal fistulizing CD treated with UST or IFX was conducted to evaluate the rates of luminal and perianal fistula response and remission at 6 months after treatment.
Results
Ninety-seven patients (49 UST and 48 IFX) were enrolled. Compared to IFX, UST exhibited significantly higher rates of treatment success (89.8% vs. 50.0%, P< 0.001) and intestinal clinical response (85.7% vs. 68.8%, P= 0.048), but no significant differences in fistula remission, fistula response, fistula closure, intestinal clinical remission, endoscopic remission and endoscopic response was observed. Furthermore, multivariate analyses demonstrated complexity of fistula was conversely associated with fistula remission between the UST and IFX groups. Finally, the rates of disease relapse and operation in the IFX group were higher as compared to the UST group during follow-up.
Conclusions
UST may serve as a promising alternative to IFX for the treatment of perianal fistulizing CD.

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IBD

The prevalence of pouch fistulas in ulcerative colitis following restorative proctocolectomy: a systematic review and meta-analysis: Sheng Wei Lo, Ishaan Dharia, Danujan Sriranganathan, Maia Kayal, Edward L. Barnes, Jonathan P. Segal; Intest Res 2025;23(1):56-64. Published online August 9, 2024; DOI: https://doi.org/10.5217/ir.2024.00009

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
One complication of restorative proctocolectomy with ileo-anal pouch anastomosis is fistula formation in the pouch. Fistulas can be associated with significant morbidity and pouch failure. We conducted a systematic review with meta- analysis to try and understand the prevalence of pouch fistulas in patients with ulcerative colitis following restorative proctocolectomy.
Methods
The Embase, Embase Classic, and PubMed databases were searched between January 1979 and April 2022. Studies were included if there were cross-sectional, case-controlled, population-based or cohort studies reporting on prevalence of pouch fistulas in ulcerative colitis. Studies had to report the number of patients with pouch fistulas using either clinical, endoscopic, or radiological diagnosis in an adult population.
Results
Thirty-three studies screened met the inclusion criteria. The pooled prevalence of developing at least 1 fistula was 0.05 (95% confidence interval [CI], 0.04–0.07). The pooled prevalence of pouch failure in patients with pouch fistula was found to be 0.24 (95% CI, 0.19–0.30). The pooled prevalence of developing a pouch fistula at 3 years, 5 years and more than 5 years was 0.04 (95% CI, 0.02–0.07), 0.05 (95% CI, 0.02–0.07), and 0.05 (95% CI, 0.02–0.10), respectively.
Conclusions
This is the first systematic review and meta-analysis to report the prevalence of pouch fistula. It also provides a pooled prevalence of pouch failure in these patients. These results can help to shape future guidelines, power future studies, and help counsel patients.

Citations

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Minimally Invasive Rectal Surgery: Current Status and Future Perspectives in the Era of Digital Surgery
Marta Goglia, Matteo Pavone, Vito D’Andrea, Veronica De Simone, Gaetano Gallo
Journal of Clinical Medicine.2025; 14(4): 1234. CrossRef

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IBD

Perianal fistulizing lesions of Crohn’s disease are associated with long-term behavior and its transition: a Chinese cohort study: Wei Zhan, Xiaoyin Bai, Hong Yang, Jiaming Qian; Intest Res 2024;22(4):484-495. Published online July 15, 2024; DOI: https://doi.org/10.5217/ir.2024.00021

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Crohn’s disease (CD) has a progressive nature and commonly perianal involvement. The aim of this study is to assess the prevalence, surgical treatment, and outcome of perianal fistulizing CD with associated risk factors in a large Chinese cohort.
Methods
Hospitalized patients diagnosed with CD in our center were consecutively enrolled between January 2000 and December 2018. Transition of disease behavior was classified according to the presence or absence of penetrating behavior (B3 in the Montreal classification) at diagnosis and at a median follow-up of 102 months.
Results
A total of 504 patients were included, of whom 207 (41.1%) were classified as B3 and 348 (69.0%) as L2/3 at follow-up. Transition of behavior to B3 was observed in 86 patients (17.1%). The incidence of perianal fistulizing lesions was 10.9% at 10 years with a final prevalence of 27.0% (n = 136) at the end of follow-up. Multivariate Cox regression identified independent risks of perianal fistulizing lesions for persistent B3 (hazard ratio, 4.72; 95% confidence interval, 1.91–11.66) and behavior transition of progressed to B3 (hazard ratio, 9.90; 95% confidence interval, 4.60–21.33). Perianal surgical treatments were performed in 104 patients (20.6%). Thirty-six cases (7.1%) were refractory, and it is independently associated with behavior of persistent B3 (P= 0.011).
Conclusions
Perianal fistulizing lesions occurred frequently in Chinese CD patients. Its incidence and refractory outcome were closely associated with the penetrating CD behavior. An additional risk of perianal fistulizing lesions was indicated for CD patients with behavior of progressing to B3, suggesting further attention.

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IBD

Vedolizumab for perianal fistulizing Crohn’s disease: systematic review and meta-analysis: Fares Ayoub, Matthew Odenwald, Dejan Micic, Sushila R. Dalal, Joel Pekow, Russell D. Cohen, David T. Rubin, Atsushi Sakuraba; Intest Res 2022;20(2):240-250. Published online February 8, 2022; DOI: https://doi.org/10.5217/ir.2021.00091

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Perianal fistulas are a debilitating manifestation of Crohn’s disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management of fistulizing CD continues to be challenged by unmet needs. We conducted a systematic review and meta-analysis of the effectiveness of vedolizumab for the management of perianal fistulizing CD.
Methods
A search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model.
Results
A total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%–37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%–47.7%) with high heterogeneity (I2=67.1%).
Conclusions
In a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.

Citations

Citations to this article as recorded by

How to Approach the Difficult Perineum in Crohn's Disease
Emily Rinebold, Alex L. Huang, Sue J. Hahn
Clinics in Colon and Rectal Surgery.2025; 38(02): 148. CrossRef
Fistula in Crohn’s disease: classification, pathogenesis, and treatment options
Kimia Basiji, Nesa Kazemifard, Maryam Farmani, Kasra Jahankhani, Shaghayegh Baradaran Ghavami, Amir Fallahnia, Hesameddin Eghlimi, Adil Mir
Tissue Barriers.2025;[Epub] CrossRef
Perianal Crohn's disease: the experience of taking a multiprofessional approach in a tertiary centre setting
Eathar Shakweh, Johncy Baby, Lisa Younge, Phil Tozer, Ailsa Hart
British Journal of Nursing.2025; 34(8): 406. CrossRef
ACG Clinical Guideline: Management of Crohn's Disease in Adults
Gary R. Lichtenstein, Edward V. Loftus, Anita Afzali, Millie D. Long, Edward L. Barnes, Kim L. Isaacs, Christina Y. Ha
American Journal of Gastroenterology.2025; 120(6): 1225. CrossRef
Management of Perianal Fistulizing Crohn’s Disease
Arshdeep Singh, Vandana Midha, Gursimran Singh Kochhar, Bo Shen, Ajit Sood
Inflammatory Bowel Diseases.2024; 30(9): 1579. CrossRef
Choosing Therapy for Moderate to Severe Crohn’s Disease
Malcolm Irani, Bincy Abraham
Journal of the Canadian Association of Gastroenterology.2024; 7(1): 1. CrossRef
Perianal fistulizing Crohn’s disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies
Jalpa Devi, David H. Ballard, Tina Aswani-Omprakash, Alyssa M. Parian, Parakkal Deepak
Indian Journal of Gastroenterology.2024; 43(1): 48. CrossRef
Clinical use of biologics for Crohn’s disease in adults: lessons learned from real-world studies
Antonio Tursi, Giammarco Mocci, Angelo Del Gaudio, Alfredo Papa
Expert Opinion on Biological Therapy.2024; 24(3): 171. CrossRef
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Manish Manrai, Atul Abhishek Jha, Saurabh Dawra, Aditya Vikram Pachisia
Future Pharmacology.2024; 4(1): 279. CrossRef
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Mohammad Shehab, Davide De Marco, Peter L. Lakatos, Talat Bessissow
Expert Opinion on Biological Therapy.2024; 24(8): 733. CrossRef
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Klaudia Farkas, Hajnal Székely, Péter Bacsur, Balázs Bánky, Zsuzsa Bianka Élthes, László Harsányi, Katalin Edit Müllner, Ágnes Milassin, Károly Palatka, Patrícia Sarlós, Tamás Szamosi, Tamás Molnár, Pál Miheller
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The Optimal Management of Fistulizing Crohn’s Disease: Evidence beyond Randomized Clinical Trials
Panu Wetwittayakhlang, Alex Al Khoury, Gustavo Drügg Hahn, Peter Laszlo Lakatos
Journal of Clinical Medicine.2022; 11(11): 3045. CrossRef
Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease
Jan Marsal, Manuel Barreiro-de Acosta, Irina Blumenstein, Maria Cappello, Thomas Bazin, Shaji Sebastian
Frontiers in Medicine.2022;[Epub] CrossRef
Management of inflammatory bowel disease beyond tumor necrosis factor inhibitors: novel biologics and small-molecule drugs
Soo-Young Na, You Sun Kim
The Korean Journal of Internal Medicine.2022; 37(5): 906. CrossRef

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Reviews

IBD

Correlation of serum levels of anti-tumor necrosis factor agents with perianal fistula healing in Crohn’s disease: a narrative review: Eron Fabio Miranda, Rodrigo Bremer Nones, Paulo Gustavo Kotze; Intest Res 2021;19(3):255-264. Published online November 6, 2020; DOI: https://doi.org/10.5217/ir.2020.00029

Abstract PDF PubReader ePub

With the overspread use of measurement of serum levels of anti-tumor necrosis factor (TNF) agents (therapeutic drug monitoring, TDM), new therapeutic strategies have been used in the management of Crohn’s disease (CD). Different targets are correlated with increased levels of circulating drugs. Recent evidence demonstrated that higher serum levels of anti-TNF agents may be associated to better outcomes in perianal fistulizing CD (PFCD). Overall, patients with healed fistulas had higher serum levels of infliximab and adalimumab as compared to those with active drainage. This was demonstrated in some cohort studies, in induction and maintenance, in adults and children with PFCD. In this narrative review, authors summarize current evidence on the use of serum level measurement of anti-TNF agents and its correlation with perianal fistula healing in CD patients. Data on the use of TDM in PFCD is discussed in detail. The retrospective design of the studies and the lack of objective parameters to measure fistula healing are the main limitations of published data. Prospective studies, with central reading of objective radiological parameters, such as pelvic magnetic resonance imaging scores, can improve the level of evidence on the possible advantages of TDM in perianal fistula in CD and are warranted.

Citations

Citations to this article as recorded by

Management of Perianal Fistulizing Crohn’s Disease
Arshdeep Singh, Vandana Midha, Gursimran Singh Kochhar, Bo Shen, Ajit Sood
Inflammatory Bowel Diseases.2024; 30(9): 1579. CrossRef
Evaluating the Efficacy of Infliximab in Inflammatory Bowel Disease: A Systematic Review of the Literature
Maria P Vallejo, Arturo P Jaramillo, Carlos Luis Guanín Cabrera, Maria G Cueva, Mario Navarro Grijalva, Xavier Grandes
Cureus.2024;[Epub] CrossRef
Comparison of the Pharmacokinetics of CT-P13 Between Crohn’s Disease and Ulcerative Colitis
Eun Soo Kim, Sung Kook Kim, Dong Il Park, Hyo Jong Kim, Yoo Jin Lee, Ja Seol Koo, Eun Sun Kim, Hyuk Yoon, Ji Hyun Lee, Ji Won Kim, Sung Jae Shin, Hyung Wook Kim, Hyun-Soo Kim, Young Sook Park, You Sun Kim, Tae Oh Kim, Jun Lee, Chang Hwan Choi, Dong Soo Ha
Journal of Clinical Gastroenterology.2023; 57(6): 601. CrossRef
Early Infliximab Trough Levels Predict the Long-term Efficacy of Infliximab in a Randomized Controlled Trial in Patients with Active Crohn’s Disease Comparing, between CT-P13 and Originator Infliximab
Jihye Park, Jae Hee Cheon, Kang-Moon Lee, Young-Ho Kim, Byong Duk Ye, Chang Soo Eun, Sung Hyun Kim, Sun Hee Lee, Joon Ho Lee, Stefan Schreiber
Gut and Liver.2023; 17(3): 430. CrossRef
Therapeutic Drug Monitoring in Perianal Fistulizing Crohn’s Disease
Mir Zulqarnain, Parakkal Deepak, Andres J. Yarur
Journal of Clinical Medicine.2022; 11(7): 1813. CrossRef
Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease
Jan Marsal, Manuel Barreiro-de Acosta, Irina Blumenstein, Maria Cappello, Thomas Bazin, Shaji Sebastian
Frontiers in Medicine.2022;[Epub] CrossRef
Editorial: higher concentrations of cytokine blockers are needed to obtain small bowel mucosal healing during maintenance therapy in Crohn's disease
Shana Rakowsky, Adam S. Cheifetz, Konstantinos Papamichael
Alimentary Pharmacology & Therapeutics.2021; 54(8): 1085. CrossRef

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IBD

An overview of the role of exclusive enteral nutrition for complicated Crohn’s disease: Mustafa Adamji, Andrew S Day; Intest Res 2019;17(2):171-176. Published online December 3, 2018; DOI: https://doi.org/10.5217/ir.2018.00079

Abstract PDF PubReader ePub

The role and efficacy of exclusive enteral nutrition (EEN) in the treatment of luminal Crohn’s disease (CD) has been well established over the last 2 decades. Consequently, in many centers nutritional therapy is now considered first line therapy in the induction of remission of active CD. However, the use of nutritional therapy in complicated CD has yet to be fully determined. This article aimed to review case reports and clinical trials published in the last decade that have considered and evaluated nutritional therapy in the setting of complicated CD in children and adults. Published literature focusing upon the use of nutritional therapy as part of medical therapy in the management of complicated CD were identified and reviewed. Although there continue to be various interventions utilized for complicated CD, the currently available literature demonstrates that nutritional therapies, especially EEN, have important roles in the management of these complex scenarios. Further assessments, involving large numbers of patients managed with consistent approaches, are required to further substantiate these roles.

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Original Articles

IBD

Intraoperative inspection alone is a reliable guide to the choice of surgical procedure for enteroenteric fistulas in Crohn's disease: Zhen Guo, Xingchen Cai, Ruiqing Liu, Jianfeng Gong, Yi Li, Lei Cao, Weiming Zhu; Intest Res 2018;16(2):282-287. Published online April 30, 2018; DOI: https://doi.org/10.5217/ir.2018.16.2.282

Abstract PDF PubReader ePub

Background/Aims

Resection of the diseased segment and suture of the victim segment is recommended for enteroenteric fistula in Crohn's disease (CD). The main difficulty in this procedure remains reliable diagnosis of the victim segment, especially for fistulas found intraoperatively and inaccessible on endoscopic examination. We aimed to explore whether intraoperative inspection alone is reliable.

Methods

Patients undergoing conservative surgery between 2011 and 2016 for enteroenteric fistulas complicating CD were identified from a prospectively maintained database. Patients were divided according to whether the victim segment was evaluated by preoperative endoscopy + intraoperative inspection (PI group) or by intraoperative inspection alone (I group). Outcomes were compared.

Results

Of 65 patients eligible for the study, 37 were in in the PI group and 28 were in the I group. The baseline characteristics were similar between the groups, except for the rate of emergency surgery (0/37 in PI group vs. 5/28 in I group, P=0.012). Fistulas involved more small intestines (4/37 in PI group vs. 15/28 in I group, P<0.001) and fewer sigmoid colons (17/37 in PI group vs. 4/28 in I group, P=0.008) in I group due to accessibility with endoscopy. No difference was found in postoperative complications, stoma rates, postoperative recurrence, or disease at the repair site between the 2 groups (P>0.05).

Conclusions

For fistulas found intraoperatively and inaccessible on endoscopic examination, intraoperative inspection was a reliable guide when choosing between en bloc resection and a conservative procedure.

Citations

Citations to this article as recorded by

Diagnosis and Classification of Fistula from Inflammatory Bowel Disease and Inflammatory Bowel Disease-Related Surgery
Sarah Householder, Joseph A. Picoraro
Gastrointestinal Endoscopy Clinics of North America.2022; 32(4): 631. CrossRef

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Clinical efficacy of adalimumab versus infliximab and the factors associated with recurrence or aggravation during treatment of anal fistulas in Crohn's disease: Cheng-Chun Ji, Shota Takano; Intest Res 2017;15(2):182-186. Published online April 27, 2017; DOI: https://doi.org/10.5217/ir.2017.15.2.182

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Background/Aims

Infliximab has proven to be effective in the treatment of perianal fistulas in Crohn's disease (CD) but the efficacy of adalimumab is still unclear. The aim of this study is to assess the clinical efficacy of adalimumab and compare the results with those for infliximab.

Methods

Forty-seven CD patients treated for perianal fistulas with infliximab from September 2005 to December 2010 (n=31), or with adalimumab from November 2010 to May 2012 (n=16), were enrolled in this retrospective study. The following patient characteristics were analyzed; intestinal lesion site, fistula classification, seton placement, index of inflammatory bowel disease, C-reactive protein level, follow-up period, and the cumulative rate of nonrecurrence or aggravation of fistula.

Results

There were no significant differences in the intestinal lesion site, fistula classification, inflammatory bowel disease index, C-reactive protein level, and the frequency of injection between the infliximab group and the adalimumab group. The cumulative rate of nonrecurrence or aggravation of fistula was 62.5% in the adalimumab group and 83.9% in the infliximab group at 24 months after treatment (P=0.09). The risk factors for recurrence or aggravation may be related to seton placement (P=0.02), gender (P=0.06), and fistula classification (P=0.07).

Conclusions

There was no significant difference in the clinical efficacy of adalimumab and infliximab in the treatment of perianal fistulas in CD. However, fistula classification may be an important risk factor for recurrence or aggravation. The preliminary findings in this study show that further research is warranted.

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Case Reports

Two Cases of Gastrocolocutaneous Fistula with a Long Asymptomatic Period after Percutaneous Endoscopic Gastrostomy: Hyo Sun Kim, Chang Seok Bang, Yeon Soo Kim, Oh Kyung Kwon, Min Sun Park, Jeong Ho Eom, Gwang Ho Baik, Dong Joon Kim; Intest Res 2014;12(3):251-255. Published online July 25, 2014; DOI: https://doi.org/10.5217/ir.2014.12.3.251

Abstract PDF PubReader ePub

Gastrocolocutaneous fistula is a rare complication of the percutaneous endoscopic gastrostomy (PEG) procedure. Typical symptoms usually occur in the first few months. We recently encountered 2 patients with 8- and 33-month asymptomatic periods. A 74-year-old man presented with watery diarrhea for 1 month. He had undergone PEG 9 months earlier. During workup, an upper endoscopy and abdominal CT scan revealed the migration of the feeding tube into the transverse colon. He was discharged with a nasogastric tube after treatment. A 77-year-old man presented with sudden loosening of his PEG tube with a duration over 3 days. He had undergone PEG procedure three times until that time. During workup, a gastrocolocutaneous fistula was diagnosed. However, when previous studies were reviewed, an abdominal CT scan, which was done 6 months ago before the third PEG, showed the fistula already existed at that time, suggesting that it was created about 33 months earlier when he underwent the second PEG procedure. The patient died of pneumonia aggravation despite conservative treatment. Both a high index of suspicion and the careful inspection of the upper endoscopy are very important for early diagnosis regardless of symptoms.

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Shutaro Gunji, Hokahiro Katayama, Shigehiro Morikawa, Aaron Tan
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Arsalan Rafiq, Naeem Abbas, Hassan Tariq, Suresh Kumar Nayudu
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Successful Treatment of Postoperative Fistula with Infliximab in a Patient with Crohn's Disease: Seong Yeon Jeong, Jeong Seop Moon, Kyu Joo Park, You Sun Kim; Intest Res 2014;12(1):74-77. Published online January 28, 2014; DOI: https://doi.org/10.5217/ir.2014.12.1.74

Abstract PDF PubReader

Nearly 80% of patients with Crohn's disease (CD) require surgical treatment for complications or failure of medical management. We managed a 31-year-old man with CD who presented with a post-operative fistula. The patient had undergone surgery due to multiple strictures and a fistula. However, a new fistula developed that connected to the intraperitoneal abscess. Intravenous antibiotics were started and multiple percutaneous drainage tubes were inserted to treat the abdominal abscess. However, the amount of drainage was consistently high, even one month after the operation. To treat the postoperative fistula, 5 mg/kg of infliximab was started, and the amount of drainage decreased dramatically to less than 10 cc a day. Some studies have reported that infliximab decreases the recurrence of CD after surgery. The effect of infliximab on post-operative fistulas in patients with CD has not been sufficiently studied. Our results indicated that the use of infliximab to treat post-operative fistula should be explored further in future clinical studies.

Citations

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Treatment of abdominal fistulas in Crohn�s disease and monitoring with abdominal ultrasonography
Nadia Moreno Sánchez, José María Paredes, Tomas Ripollés, Javier Sanz de la Vega, Patricia Latorre, María Jesús Martínez, José Richart, José Vizuete, Eduardo Moreno-Osset
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BMC Gastroenterology.2015;[Epub] CrossRef

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