Epidemiology, treatment patterns, and associated risk factors in perianal fistulizing Crohn's disease: A systematic literature review

Abstract

Background: Data regarding complex Crohn's perianal fistulas (CPF) epidemiology are limited, and optimal treatment strategies are elusive. An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development, treatment failure, and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies, reduce treatment burden, and improve outcomes in patients with CPF.

Aim: To describe the epidemiology, treatments, outcomes, and associated risk/protective factors for complex CPF.

Methods: Electronic databases (MEDLINE, EMBASE, EBM Reviews, EconLit) were searched. Two reviewers independently used populations, interventions, comparators, outcomes, study designs, and time criteria to identify relevant studies. Observational studies published in English from January 1, 2015 to February 17, 2022 with > 50 patients were included, even if complex CPF was not defined. Items of interest included complex CPF definitions, epidemiology, treatment patterns, morbidity, mortality, and risk factors associated with complex CPF development, treatment failure, and undergoing multiple surgeries. Data were reported using descriptive statistics.

Results: Overall, 140 studies were included. Complex CPF definitions were heterogeneous and rarely reported (24 studies). Hence, data mostly related to CPF in general. CPF prevalence was variable (range: 1.5%-81.0%). Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn's disease diagnosis (range: 3.5%-50.1%). Overall healing and failure rates after treatment were in the range of 10.5%-80.2% and 3.6%-83.0%, respectively. Abscesses were the most frequently reported morbidity (n = 18). No CPF-related deaths were reported. No consistent risk or protective factors were identified.

Conclusion: Epidemiology, treatment patterns, and risk factors for CPF vary, likely due to inconsistent CPF and clinical outcome definitions. Standardization would facilitate comparability, which may inform optimal complex CPF treatment strategies.

Keywords: Complex perianal fistula; Crohn’s disease; Epidemiology; Morbidity; Risk factors; Treatment patterns.

Figure 1

Crohn’s perianal fistula prevalence in adult, pediatric, and mixed populations across study types and geographical location. Data are presented as range (interquartile range) for study type and median [range (interquartile range)] for geographical region. Only studies reporting relevant data are included.

Figure 2

Proportions of patients with Crohn’s perianal fistulas receiving one of the top five most frequently reported interventions used as first, second, or third treatment within a study. Numbers in the key represent the number of studies reporting the intervention as the first, second, and/or third treatment in a study; some studies reported an intervention in more than one line of treatment. Numbers above the bars are median (interquartile range) proportion of patients; number of studies. Loose seton was not reported as a third treatment in any studies. IQR: Interquartile range.

Figure 3

Treatment algorithms showing the first, second, third, and fourth treatments among studies showing sequential treatments (n = 15). The first treatment in a study is presented on the left of the figure with the number of corresponding treatment algorithms. The lines then flow to the next treatment mentioned in the studies; line thickness corresponds to the number of treatment lines. Of note one study may report more than one treatment per line; for example, one study by Graf et al[49] reported that patients underwent loose seton placement as a first treatment followed by fistulectomy/-otomy, advancement flap, or plug, representing three different treatments as a second treatment in this study.