Evaluating the Comparative Effectiveness of Medical Therapy for Prevention of Perianal Fistula Development in Pediatric Crohn's Disease

Project start date and end date: 2017 to 2019

Background:
Gastrointestinal fistulas are abnormal connections between the bowel and adjacent structures such as the skin, bladder, vagina, fallopian tubes, or to other loops of bowel, most commonly to the perianal region. Perianal fistulas are a major cause of morbidity among patients with Crohn’s disease and have significant negative impact on their quality of life. Perianal fistulas cause severe infections, fecal incontinence, perianal discharge, negative self-image, and social isolation; they can lead to infertility and the need for numerous surgeries. Perianal fistulas commonly occur among 26-36% of adults with Crohn’s, often causing serious, debilitating complications that are difficult to treat, leading to increased costs. Onset of Crohn’s disease in childhood may be associated with more aggressive fistula development, although very limited data on the incidence and prevalence of pediatric fistulas are available.

It is not known why some children with Crohn’s disease develop perianal fistulas while others do not, nor the extent to which this risk can be modified. There is wide variation in treatment methods for Crohn’s disease, and it is unknown whether any particular Crohn’s treatment, or sequence of treatments, is effective at preventing perianal fistula development. The few population-based studies that have been conducted have been based on samples too small to determine associations with medication usage. To date, large administrative database studies have not been used to address this gap, largely because claims-based methodologies typically employed in prior studies suffer from both poor sensitivity and specificity. We have recently validated a new claims-based methodology to accurately identify Crohn’s perianal fistulas; this development enables larger-scale application. Building on our prior work, this new methodology can be applied using national administrative claims databases to evaluate treatment methods for Crohn’s disease among a broad population of children. Understanding the comparative effectiveness of Crohn’s treatments on subsequent perianal fistula development is vital to advancing new strategies for the prevention of perianal fistulas.

Objectives:

• Aim 1: To determine the relative contribution of factors associated with perianal fistulas among pediatric patients with Crohn’s disease in a national administrative claims database.
• Aim 2: To determine medications associated with prevention or delay in perianal fistula development.

Research Topics & Methods:

• In order to have a sufficiently large sample to determine these associations, we will employ the OptumInsight Clinformatics Data Mart (Optum), a commercial claims database that includes inpatient, outpatient, and procedure claims records for over 12 million pediatric members located in all 50 states. We will conduct a retrospective claims analysis in which we will characterize perianal fistula development among pediatric Crohn’s disease patients in this commercial claims database. We will apply our validated method for identifying patients who develop perianal fistulas. We will then identify the relative contribution of patient and treatment factors toward risk of fistula development.

Implications:
If we can determine the relationship between medication treatment and subsequent risk of perianal fistula development among pediatric patients with Crohn’s disease, then this study will provide critically needed information about the comparative effectiveness of medications for preventing fistula complications of Crohn’s disease.

Funder:
This project is funded by the National Institutes of Health / National Institute of Diabetes and Digestive and Kidney Diseases.

Collaborators:
Chun Chieh Lin; Samir K. Gadepalli; Kevin J. Dombkowski