Pediatr Res. 2023 May;93(6):1659-1666. doi: 10.1038/s41390-022-02270-x. Epub 2022 Aug 25.

Tereza Lerchova ^# 1, Ondrej Hradsky ^# 2, Michal Kulich ³, Gabor Veres ⁴, Jorge Amil Dias ⁵, Malgorzata Sladek ⁶, Sanja Kolacek ⁷, Stephanie Van Biervliet ⁸, Jan Melek ⁹, Daniela E Serban ¹⁰, Katrine Winther ¹¹, Tim de Meij ¹², Jan Schwarz ¹³, Kaija-Leena Kolho ¹⁴, Johanna C Escher ¹⁵, Jiri Bronsky ²

Author information

• ¹Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. terezadrskova@gmail.com.
• ²Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
• ³Department of Probability and Mathematical Statistics, Faculty of Mathematics and Physics, Charles University, Prague, Czech Republic.
• ⁴Pediatric Institute-Clinic, University of Debrecen, Debrecen, Hungary.
• ⁵Hospital S. Joao do Porto, Porto, Portugal.
• ⁶Polish-American Children's Hospital, Jagiellonian University, Cracow, Poland.
• ⁷Children's Hospital Zagreb Faculty of Medicine, Zagreb, Croatia.
• ⁸Ghent University Hospital, Ghent, Belgium.
• ⁹Department of Pediatrics, University Hospital, Charles University, Hradec Kralove, Czech Republic.
• ¹⁰2nd Clinic of Pediatrics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Emergency Clinical Hospital for Children, Cluj-Napoca, Romania.
• ¹¹Hvidovre Hospital, Copenhagen, Denmark.
• ¹²Amsterdam UMC, location VUMC, Amsterdam, Netherlands.
• ¹³Department of Pediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
• ¹⁴Children's Hospital, University of Helsinki, Helsinki, Finland.
• ¹⁵Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands.

^#Contributed equally.

Abstract

Background: Maintaining of remission early in the disease course of Crohn's disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy.

Methods: This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse.

Results: Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59-2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031).

Conclusions: Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision.

Impact: The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed.