Improved clinical outcomes with early anti-tumour necrosis factor alpha therapy in children with newly diagnosed Crohn's disease: real world data from the international prospective PIBD-SETQuality inception cohort study

Renz C W Klomberg; Hella C van der Wal; Martine A Aardoom; Polychronis Kemos; Dimitris Rizopoulos; Frank M Ruemmele; Mohammed Charrout; J C Escher; Nicholas M Croft; Lissy de Ridder; PIBD-SETQuality collaborative group; Ivan D Milovanovich; James J Ashton; Paul Henderson; Oren Ledder; Tim G J de Meij; Richard Hansen; Thalia Z Hummel; Katsuhiro Arai; Astor Rodrigues; Fiona Cameron; Sibylle Koletzko; Rafeeq Muhammed; Natalia Nedelkopoulou

doi:10.1093/ecco-jcc/jjad197

Improved clinical outcomes with early anti-tumour necrosis factor alpha therapy in children with newly diagnosed Crohn's disease: real world data from the international prospective PIBD-SETQuality inception cohort study

J Crohns Colitis. 2023 Nov 27:jjad197. doi: 10.1093/ecco-jcc/jjad197. Online ahead of print.

Authors

Renz C W Klomberg¹, Hella C van der Wal¹, Martine A Aardoom¹, Polychronis Kemos², Dimitris Rizopoulos³, Frank M Ruemmele⁴, Mohammed Charrout⁵, J C Escher¹, Nicholas M Croft², Lissy de Ridder¹; PIBD-SETQuality collaborative group; Ivan D Milovanovich⁶, James J Ashton⁷, Paul Henderson⁸, Oren Ledder⁹, Tim G J de Meij¹⁰, Richard Hansen¹¹, Thalia Z Hummel¹², Katsuhiro Arai¹³, Astor Rodrigues¹⁴, Fiona Cameron¹⁵, Sibylle Koletzko¹⁶, Rafeeq Muhammed¹⁷, Natalia Nedelkopoulou¹⁸

Affiliations

¹ Department of Pediatric Gastroenterology, Sophia Children's Hospital, Rotterdam, The Netherlands.
² Pediatric Gastroenterology, Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
³ Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
⁴ Department of Pediatric Gastroenterology, Université Paris Descartes, Sorbonne Paris Cité, APHP, Hôpital Necker Enfants Malades, Paris, France.
⁵ Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands.
⁶ Department of Gastroenterology, Hepatology, and Endoscopy, University Children's Hospital, Belgrade, Serbia.
⁷ Department of Paediatric Gastroenterology, Southampton Children's Hospital, Southampton, United Kingdom, Human Genetics and Genomic Medicine, University of Southampton, Southampton, United Kingdom.
⁸ Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, United Kingdom, Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom.
⁹ Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
¹⁰ Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, the Netherlands.
¹¹ Clinical Reader in Child Health, Department of Child Health, Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, Scotland, Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, Scotland.
¹² Department of Paediatric Gastroenterology, Medisch Spectrum Twente, Enschede, the Netherlands.
¹³ Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan.
¹⁴ Department of Paediatric Gastroenterology, Oxford Children's Hospital, Oxford, United Kingdom.
¹⁵ Department of Pediatric Gastroenterology, Hepatology and Nutrition, Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
¹⁶ Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany, Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.
¹⁷ Department of Paediatric Gastroenterology, Birmingham Children's Hospital, Birmingham, United Kingdom.
¹⁸ Department of Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, United Kingdom.

PMID: 38011797
DOI: 10.1093/ecco-jcc/jjad197

Abstract

Background & aims: Treatment guidelines for paediatric Crohn's disease (CD) suggest early use of anti-tumour necrosis factor alpha (anti-TNF) in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort.

Methods: Children with newly-diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF (<90 days after diagnosis) and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission (SSFR) without treatment intensification (specified as SSFR*) and sustained steroid-free mild/inactive disease without treatment intensification (specified as SSFMI*). Penalised logistic regression model-based standardisation was applied to estimate the relative risks (RR) of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients based on presence of predictors of poor outcome (POPOs) and disease activity at diagnosis.

Results: In total, 331 children (median age 13.9 years [IQR 12.2 - 15.3]) were enrolled, with 135 (41%) receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* (30% vs. 14%, p<0.001) and SSFMI* (69% vs. 33%, p<0.001), with RRs of 2.95 (95%CI 1.63-5.36) and 4.67 (95%CI 2.46-8.87) respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared to mild/inactive disease at diagnosis (5.50 [95%CI 2.51-12.05]) vs. 2.91 [95%CI 0.92-9.11]), and those with any POPO compared to no POPO (5.05 [95%CI 2.45-10.43] vs. 3.41 [95%CI 0.54-21.7]).

Conclusion: In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients.

Keywords: biologics; early treatment; inflammatory bowel disease; risk-stratification.