Complicated Disease and Response to Initial Therapy Predicts Early Surgery in Paediatric Crohn’s Disease: Results From the Porto Group GROWTH Study

Author:

Levine Arie1,Chanchlani Neil2ORCID,Hussey Seamus3,Ziv-Baran Tomer4,Escher Johanna C5,Amil Dias Jorge6,Veres Gabor7,Koletzko Sibylle8,Turner Dan9,Kolho Kaija-Leena10,Paerregaard Anders11,Staiano Annamaria12,Lionetti Paolo13,Nuti Federica1415,Sladek Malgorata16,Shaoul Ron17,Lazowska-Prezeorek Isabella18,Martin de Carpi Javier19,Sigall Boneh Rotem1,Pfeffer Gik Tamar1,Cohen-Dolev Noa1,Russell Richard K20

Affiliation:

1. Paediatric Gastroenterology and Nutrition Unit, Tel Aviv University, Edith Wolfson Medical Center, Holon, Israel

2. Exeter IBD Pharmacogenetics, RILD building, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK

3. National Children’s Research Centre, Crumlin; Department of Paediatrics, UCD and RCSI, Dublin, Ireland

4. School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel

5. Erasmus MC-Sophia Children’s Hospital, Pediatric Gastroenterology, Rotterdam, Netherlands

6. Pediatric Gastroenterology Unit, Centro Hospitalar de São João, Porto, Portugal

7. Pediatric Institute, University of Debrecen, Hungary

8. Ludwig Maximilians-Universität München, Dr. von Hauner Children’s Hospital, Munich, Germany

9. Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel

10. University of Tampere, Tampere, Finland and Children’s Hospital, Helsinki, Finland

11. Department of Paediatrics 460, Hvidovre University Hospital, Denmark

12. Department of Translational Medical Science, Section of Pediatrics, University of Naples ‘Federico II’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

13. University of Florence-Meyer Hospital, Florence, Italy

14. Intermediate Pediatric Care Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy

15. Pediatric Gastroenterology and Hepatology Unit, Sapienza University Rome, Italy

16. Jagiellonian University Medical College, Krakow, Poland

17. Rambam Medical Center, Haifa, Israel

18. Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Poland

19. Department of Pediatric Gastroenterology, Hepatology and Nutritiom, Hospital Sant Joan de Déu, Barcelona, Spain

20. Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, UK

Abstract

Abstract Introduction The ability to predict risk for poor outcomes in Crohn’s disease [CD] would enable early treatment intensification. We aimed to identify children with CD with complications at baseline and throughout the study period who are at risk for surgery 2 years from diagnosis. Methods Newly diagnosed children with CD were enrolled into a prospective, multicentre inception cohort. Disease characteristics and serological markers were obtained at baseline and week 12 thereafter. Outcome data including disease activity, therapies, complications and need for surgery were collected until the end of 104 weeks. A chi-square automatic interaction detection [CHAID] algorithm was used to develop a prediction model for early surgery. Results Of 285 children enrolled, 31 [10.9%] required surgery within 2 years. Multivariate analysis identified stricturing disease at baseline (odds ratio [OR] 5.26, 95% confidence interval [CI] 2.02–13.67 [p = 0.001]), and Paediatric Crohn’s Disease Activity Index [PCDAI] >10 at week 12 (OR 1.06, 95% CI 1.02–1.10 [p = 0.005]) as key predictors for early surgery. CHAID demonstrated that absence of strictures at diagnosis [7.6%], corticosteroid-free remission at week 12 [4.1%] and early immunomodulator therapy [0.8%] were associated with the lowest risk of surgery, while stricturing disease at diagnosis [27.1%, p < 0.001] or elevated PCDAI at week 12 [16.7%, p = 0.014] had an increased risk of surgery at follow-up. Anti-OmpC status further stratified high-risk patients. Discussion A risk algorithm using clinical and serological variables at diagnosis and week 12 can categorize patients into high- and low-risk groups from diagnosis.

Funder

A.L. Thrasher foundation

ESPGHAN

Catherine McEwan foundation

NHS senior research fellowship

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

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