The Safety and Effectiveness of anti-TNF therapy in Internally Penetrating Crohn’s Disease

Project start date and end date: 2022 - 2023

Background:

Internally penetrating Crohn’s disease (IPCD) complications, including abscesses and phlegmon, are a significant source of morbidity among pediatric Crohn’s Disease (CD) patients. Management strategies are notably heterogeneous, stemming from a lack of adequately powered studies. Anti-tumor-necrosis-factor- (anti-TNF) biologics are the mainstay of penetrating CD therapy and are most effective early in the disease course. However, use among patients with IPCD complications is limited by hesitancy over infectious complications, limiting the feasibility of prospective studies addressing this research topic. Evidence describing the safety and effectiveness of anti-TNF therapy in the presence of IPCD complications is limited by insufficiently powered studies and lack of adequate risk adjustment.

Objective:

The project’s objective is to determine the safety and effectiveness of early anti-TNF therapy in the setting of internally penetrating Crohn’s Disease (IPCD) complications (abscesses and phlegmon) and identify clinical predictors that may aid in personalizing therapy using a multicenter cohort study design based on retrospective data collection.

Research Topics & Methods:

This multicenter retrospective cohort study is led by Principal Investigator Dr. Brad Constant from Children’s Hospital of Philadelphia, and the University of Michigan is one of 12 participating sites (U-M Site PI: Dr. Jeremy Adler). In this study we plan to: 

1) form a multi-institutional network of tertiary pediatric centers to provide adequate power, and 

2) implement sophisticated causal inference methodologies capable of adequate risk adjustment to isolate and measure the effect of anti-TNF initiation timing on infectious and CD-related serious adverse events (SAEs) in patients with IPCD complications. 

We hypothesize that anti-TNF therapy following IPCD complication diagnosis and prior to IPCD complication resolution, in the setting of antibiotics, is safe and effective in most pediatric patients with IPCD complications. Objective risk factors, including disease-phenotype and severity, medication history, and IPCD-related factors, may identify patients at an elevated risk of infectious SAEs in whom a more conservative approach should be taken.

Implications:

Through the creation of a risk stratification model optimizing safety, combined with state-of-the-art causal inference methodologies, we will pragmatically inform the treatment paradigm of IPCD complication management by determining the safety and effectiveness of pre-IPCD-resolution anti-TNF initiation. Our results will shed light on a clinical conundrum plagued by a lack of adequately powered research leading to wide practice variation, and will directly improve both short- and long-term outcomes in patients suffering from IPCD complications. This study will represent the largest cohort to address this research question. 

Funder:

Crohn’s and Colitis Foundation

For more information, please contact:
Clinical Professor, Department of Pediatrics, Division of Pediatric Gastroenterology
1500 E. Medical Center Drive
MPB D5200, Box SPC5718
Ann Arbor, MI 48109-5718
Phone
734-615-3139
Email
jeradler@umich.edu