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Learning Longitudinal Patterns and Subtypes of Pediatric Crohn Disease Treated With Infliximab via Trajectory Cluster
Andrew Chen1, Ronen Stein2,3, Robert N Baldassano2,3
1Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania.
Insights
This study identified three patient subgroups in pediatric Crohn disease (CD) with varying infliximab responses. Patients with the best response showed fewer complications and lower surgery risk, highlighting EHR data
Area of Science:
- Pediatric gastroenterology
- Immunology
- Biomarker analysis
Background:
- Pediatric Crohn disease (CD) management requires understanding individual treatment responses.
- Infliximab is a key biologic therapy for pediatric CD.
- Identifying patient subgroups with differential responses can optimize treatment strategies.
Purpose of the Study:
- To identify subgroups of pediatric CD patients with distinct responses to infliximab treatment.
- To analyze disease activity trajectories using electronic health record (EHR) data.
- To correlate subgroup classification with clinical characteristics and long-term surgical outcomes.
Main Methods:
- Retrospective study of 295 pediatric CD patients treated with infliximab for at least one year.
- Trajectory cluster analysis of longitudinal C-reactive protein (CRP) data to define subgroups.
- Comparison of patient characteristics, biomarkers (CRP, calprotectin), and surgical outcomes across identified subgroups.
- Cox regression models to assess the predictive value of subgroup classification for surgical outcomes.
Main Results:
- Three distinct patient subgroups with differential relapse-and-remission profiles were identified.
- The subgroup with the best infliximab response exhibited significantly lower rates of complicated disease phenotypes, including perianal involvement.
- This optimal response group also showed lower baseline CRP and calprotectin levels and a significantly reduced risk of IBD-related gastrointestinal surgery within 10 years.
Conclusions:
- Longitudinal EHR data can effectively characterize infliximab treatment response in pediatric CD.
- Trajectory cluster analysis reveals distinct patient subgroups with varying prognoses.
- Subgroup identification aids in predicting long-term outcomes and optimizing personalized treatment approaches for pediatric CD.
Background:
The objective of this study is to identify subgroups of pediatric Crohn disease (CD) who had differential responses to the infliximab treatment through trajectory cluster analysis of disease activity using data from electronic health records.
Methods:
We conducted a retrospective study of 295 pediatric patients with CD who had been treated with infliximab for a minimum of one year at the Center for Inflammatory Bowel Disease at The Children's Hospital of Philadelphia between January 2010 and December 2017. The evolution of disease was described, and subgroups of patients were identified using trajectory analysis of longitudinal data of C-reactive protein (CRP). We compared patient characteristics, biomarker for disease activity, and long-term surgical outcomes across subgroups. Cox regression models were used to evaluate the added value of the subgroup classification to baseline phenotype and location in prediction of long-term surgical outcomes.
Results:
We identified three subgroups of patients with differential relapse-and-remission profiles (n = 33, 65 and 197 from subgroup 1 to 3), which represented patients with a higher risk of infliximab non-response, with infliximab response but with occasional disease flares, and patients with long-term response. Patients with the best treatment response had a significantly lower frequency of complicated disease phenotypes (P = 0.01), including perianal involvement (P = 0.05), lower baseline CRP (P < 0.01) and calprotectin (P = 0.01), and lowest risk of IBD-related gastrointestinal surgery within 10 years of starting treatment (P < 0.01).
Conclusions:
Readily available longitudinal data from electronic health records can be leveraged to provide deeper characterization of treatment response in pediatric CD.
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