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
Research background

Perianal fistulas occur in an estimated 26% of patients with Crohn’s disease (CD) in the two decades following diagnosis, and 70% to 80% of these fistulas are complex perianal fistulas (CPF). CPF involve the upper part of the sphincter complex, have multiple external openings (tracts), are associated with pain or fluctuation suggesting a perianal abscess, and/or are associated with a rectovaginal fistula or anorectal stricture. The available evidence, while limited, suggests that CPF can result in significantly diminished health-related quality of life (HRQOL) and considerable disease burden. Understanding disease burden and unmet needs for patients with CPF may inform the development of more effective treatment strategies in this population.

Research motivation

To date, no systematic literature review evaluating the epidemiology, burden, and management of CPF in patients with CD has been conducted.

Research objectives

The objective of this study was to systematically review the literature on epidemiology, disease burden, and treatment outcomes for CD patients with CPF, thus improving understanding of the burden of CPF.

Research methods

A systematic search of electronic medical literature databases and relevant conferences was conducted in November 2016. Combinations of free text and Medical Subject Headings terms were used for the searches. The population of interest was adult (≥ 18 years) patients with CD and/or CPF undergoing medical or surgical therapy. CPF were generally defined as fistulas with intersphincteric, transsphincteric, suprasphincteric, extrasphincteric, or horseshoe tracts, although definitions of CPF varied between studies. Relevant studies reported on the epidemiology, burden, costs, treatment patterns, and/or treatment outcomes. Articles were selected by two independent researchers. Titles and abstracts of identified articles were first reviewed for relevance according to the inclusion and exclusion criteria. Full-text articles selected were then reviewed for relevance using the same criteria. Data were extracted from the included studies.

Research results

A total of 62 relevant studies were identified. Most included studies were small observational studies. The cumulative incidence of CPF in CD from two referral-centre studies was 12%-14%. CPF result in significant impairments in HRQOL. Up to 59% of patients are at risk of faecal incontinence, an outcome with significant effects on HRQOL in inflammatory bowel disease. Treatments for CPF 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 treatments commonly reported in the literature. Failure and relapse rates, respectively, for medical therapies were 12%-73% and 0%-41%; for surgical therapies were 0%-100% and 11%-20%; for combined medical and surgical therapies were 0%-80% and 0%-50%; and for allogenic adipose-derived stem cell therapies were 29%-47% and not reported). Few studies (1 of infliximab; 3 of surgical interventions) have been conducted in treatment-refractory patients, a population with considerable unmet needs.

Research conclusions

CPF in patients with CD are associated with considerable clinical and humanistic burden. Effective treatments are needed, especially for patients refractory to anti- tumour necrosis factor alpha agents, as evidenced by high failure and relapse rates with therapies evaluated in the literature.

Research perspectives

Most studies reviewed were small, observational studies. Based on the available evidence, patients with CPF face significant burden; however future research should more fully characterise the epidemiology and burden of CPF in patients with CD.