Systematic Reviews
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2018; 24(42): 4821-4834
Published online Nov 14, 2018. doi: 10.3748/wjg.v24.i42.4821
Burden and outcomes for complex perianal fistulas in Crohn’s disease: Systematic review
Julian Panes, Walter Reinisch, Ewa Rupniewska, Shahnaz Khan, Joan Forns, Javaria Mona Khalid, Daniela Bojic, Haridarshan Patel
Julian Panes, Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona 08036, Spain
Walter Reinisch, Medical University of Vienna, Vienna 1090, Austria
Ewa Rupniewska, RTI Health Solutions, Manchester M20 2LS, United Kingdom
Shahnaz Khan, RTI Health Solutions, Research Triangle Park, NC 27709, United States
Joan Forns, RTI Health Solutions, Barcelona 08028, Spain
Javaria Mona Khalid, Daniela Bojic, Haridarshan Patel, Takeda, Deerfield, IL 60015, United States
Author contributions: Patel H and Khalid JM initiated the study and secured the funding; Rupniewska E and Khan S led the literature searches; Rupniewska E, Khan S, and Forns J abstracted and analysed the data, with input from Patel H, Khalid JM, Bojic D, Panes J, and Reinisch W; Panes J, Patel H, Rupniewska E, Khan S, Forns J, Bojic D, Khalid JM, and Reinisch W interpreted the data, participated in developing the manuscript, and approved the final version of the article.
Conflict-of-interest statement: This study was conducted under a research contract between RTI Health Solutions and Takeda and was funded by Takeda. The preparation of this paper was funded by Takeda. Shahnaz Khan and Joan Forns are salaried employees of RTI Health Solutions. Ewa Rupniewska was a salaried employee of RTI Health Solutions when this research was conducted. Haridarshan Patel, Javaria Mona Khalid, Daniela Bojic are salaried employees of Takeda. Julian Panes and Walter Reinisch are consultants for Takeda.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Shahnaz Khan, MSc, RTI Health Solutions, 200 Park Offices Drive, Research Triangle Park, NC 27709, United States.
Telephone: +1-919-4852796 Fax: +1-919-5417222
Received: July 26, 2018
Peer-review started: July 26, 2018
First decision: August 27, 2018
Revised: September 24, 2018
Accepted: October 21, 2018
Article in press: October 21, 2018
Published online: November 14, 2018

To systematically review the literature on epidemiology, disease burden, and treatment outcomes for Crohn’s disease (CD) patients with complex perianal fistulas.


PubMed, Embase, and Cochrane were searched for relevant articles (published 2000-November 2016) and congress abstracts (published 2011-November 2016).


Of 535 records reviewed, 62 relevant sources were identified (mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14% (follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment (failure and relapse rates, respectively: medical, 12%-73% and 0%-41%; surgical: 0%-100% and 11%-20%; combined medical/surgical: 0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies (1 of infliximab; 3 of surgical interventions) have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.


Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to anti-tumour necrosis factor-α agents, as evidenced by high failure and relapse rates.

Keywords: Burden, Complex perianal fistulas, Crohn’s disease, Epidemiology, Outcomes, Systematic literature review, Treatment

Core tip: Complex perianal fistulas in Crohn’s disease (CD) impose considerable burden. Rates of failure and relapse are generally high with currently available treatments. Effective treatment options for complex perianal fistulas in patients with CD, especially those who are refractory to anti-tumour necrosis factor-α agents, are needed.