Response to treatment is more important than disease severity at diagnosis for prediction of early relapse in new-onset paediatric Crohn’s disease

Tomer Ziv-Baran, Séamus Hussey, Malgorzata Sladek, Jorge Amil Dias, Javier Martin de Carpi, Erasmo Miele, G. Veres, Paolo Lionetti, Sibylle Koletzko, Federica Nuti, Anders Paerregaard, Kaija Leena Kolho, Richard K. Russell, Ron Shaoul, Dror Weiner, Rotem Sigall Boneh, Johanna Escher, Lenne Finnby, Dan Turner, Arie Levine

Research output: Contribution to journalArticle

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Abstract

Background: Paediatric Crohn's disease is characteried by frequently relapsing disease which may lead to hospitalisations and complications. Aim: To develop predictive models for early relapse following first remission. Methods: The GROWTH CD prospective inception cohort was designed to predict risk for early disease relapse and poor outcomes. Newly diagnosed children underwent endoscopies and imaging. They were phenotyped and followed at scheduled visits through 78 weeks for relapses. Twenty-eight dichotomous and continuous variables were assessed at baseline and week 12, including phenotype, inflammatory markers, disease activity (PCDAI) and other markers. Clinical relapses defined as PCDAI >10 after remission were recorded using a relapse form. Logistic regression & risk modelling was performed. Results: We enrolled 282 eligible patients of whom 178 (63.6%) patients achieved steroid free remission by week 12. Disease complications developed in 22/76(29%) of patients with relapse compared to 20/206 (9.7%) without relapse (P = 0.01). Multivariable analysis demonstrated that while variables from age/gender at diagnosis were not predictive, week 12 variables including PCDAI >5 (P = 0.02), CRP >20 mg/L (P = 0.02), and faecal calprotectin >400 µg/g (P = 0.03) as optimal cut-offs were associated with increased risk of relapse. A prediction model for patients in remission including gender, age, week 12 PCDAI, calprotectin and CRP had sensitivity 43%, specificity 92%, PPV 78%, NPV 71% for relapse. Conclusions: Early relapses were associated with a higher risk for disease complications at followup. Relapse prediction based on week 12 disease activity or inflammation is superior to prediction using data from diagnosis.

Original languageEnglish
Pages (from-to)1242-1250
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume48
Issue number11-12
DOIs
Publication statusPublished - Dec 1 2018

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Recurrence
Therapeutics
Leukocyte L1 Antigen Complex
Pediatric Crohn's disease
Endoscopy
Hospitalization
Logistic Models
Steroids
Inflammation
Phenotype
Sensitivity and Specificity

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

Response to treatment is more important than disease severity at diagnosis for prediction of early relapse in new-onset paediatric Crohn’s disease. / Ziv-Baran, Tomer; Hussey, Séamus; Sladek, Malgorzata; Amil Dias, Jorge; Martin de Carpi, Javier; Miele, Erasmo; Veres, G.; Lionetti, Paolo; Koletzko, Sibylle; Nuti, Federica; Paerregaard, Anders; Kolho, Kaija Leena; Russell, Richard K.; Shaoul, Ron; Weiner, Dror; Sigall Boneh, Rotem; Escher, Johanna; Finnby, Lenne; Turner, Dan; Levine, Arie.

In: Alimentary Pharmacology and Therapeutics, Vol. 48, No. 11-12, 01.12.2018, p. 1242-1250.

Research output: Contribution to journalArticle

Ziv-Baran, T, Hussey, S, Sladek, M, Amil Dias, J, Martin de Carpi, J, Miele, E, Veres, G, Lionetti, P, Koletzko, S, Nuti, F, Paerregaard, A, Kolho, KL, Russell, RK, Shaoul, R, Weiner, D, Sigall Boneh, R, Escher, J, Finnby, L, Turner, D & Levine, A 2018, 'Response to treatment is more important than disease severity at diagnosis for prediction of early relapse in new-onset paediatric Crohn’s disease', Alimentary Pharmacology and Therapeutics, vol. 48, no. 11-12, pp. 1242-1250. https://doi.org/10.1111/apt.15016
Ziv-Baran, Tomer ; Hussey, Séamus ; Sladek, Malgorzata ; Amil Dias, Jorge ; Martin de Carpi, Javier ; Miele, Erasmo ; Veres, G. ; Lionetti, Paolo ; Koletzko, Sibylle ; Nuti, Federica ; Paerregaard, Anders ; Kolho, Kaija Leena ; Russell, Richard K. ; Shaoul, Ron ; Weiner, Dror ; Sigall Boneh, Rotem ; Escher, Johanna ; Finnby, Lenne ; Turner, Dan ; Levine, Arie. / Response to treatment is more important than disease severity at diagnosis for prediction of early relapse in new-onset paediatric Crohn’s disease. In: Alimentary Pharmacology and Therapeutics. 2018 ; Vol. 48, No. 11-12. pp. 1242-1250.
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T1 - Response to treatment is more important than disease severity at diagnosis for prediction of early relapse in new-onset paediatric Crohn’s disease

AU - Ziv-Baran, Tomer

AU - Hussey, Séamus

AU - Sladek, Malgorzata

AU - Amil Dias, Jorge

AU - Martin de Carpi, Javier

AU - Miele, Erasmo

AU - Veres, G.

AU - Lionetti, Paolo

AU - Koletzko, Sibylle

AU - Nuti, Federica

AU - Paerregaard, Anders

AU - Kolho, Kaija Leena

AU - Russell, Richard K.

AU - Shaoul, Ron

AU - Weiner, Dror

AU - Sigall Boneh, Rotem

AU - Escher, Johanna

AU - Finnby, Lenne

AU - Turner, Dan

AU - Levine, Arie

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Background: Paediatric Crohn's disease is characteried by frequently relapsing disease which may lead to hospitalisations and complications. Aim: To develop predictive models for early relapse following first remission. Methods: The GROWTH CD prospective inception cohort was designed to predict risk for early disease relapse and poor outcomes. Newly diagnosed children underwent endoscopies and imaging. They were phenotyped and followed at scheduled visits through 78 weeks for relapses. Twenty-eight dichotomous and continuous variables were assessed at baseline and week 12, including phenotype, inflammatory markers, disease activity (PCDAI) and other markers. Clinical relapses defined as PCDAI >10 after remission were recorded using a relapse form. Logistic regression & risk modelling was performed. Results: We enrolled 282 eligible patients of whom 178 (63.6%) patients achieved steroid free remission by week 12. Disease complications developed in 22/76(29%) of patients with relapse compared to 20/206 (9.7%) without relapse (P = 0.01). Multivariable analysis demonstrated that while variables from age/gender at diagnosis were not predictive, week 12 variables including PCDAI >5 (P = 0.02), CRP >20 mg/L (P = 0.02), and faecal calprotectin >400 µg/g (P = 0.03) as optimal cut-offs were associated with increased risk of relapse. A prediction model for patients in remission including gender, age, week 12 PCDAI, calprotectin and CRP had sensitivity 43%, specificity 92%, PPV 78%, NPV 71% for relapse. Conclusions: Early relapses were associated with a higher risk for disease complications at followup. Relapse prediction based on week 12 disease activity or inflammation is superior to prediction using data from diagnosis.

AB - Background: Paediatric Crohn's disease is characteried by frequently relapsing disease which may lead to hospitalisations and complications. Aim: To develop predictive models for early relapse following first remission. Methods: The GROWTH CD prospective inception cohort was designed to predict risk for early disease relapse and poor outcomes. Newly diagnosed children underwent endoscopies and imaging. They were phenotyped and followed at scheduled visits through 78 weeks for relapses. Twenty-eight dichotomous and continuous variables were assessed at baseline and week 12, including phenotype, inflammatory markers, disease activity (PCDAI) and other markers. Clinical relapses defined as PCDAI >10 after remission were recorded using a relapse form. Logistic regression & risk modelling was performed. Results: We enrolled 282 eligible patients of whom 178 (63.6%) patients achieved steroid free remission by week 12. Disease complications developed in 22/76(29%) of patients with relapse compared to 20/206 (9.7%) without relapse (P = 0.01). Multivariable analysis demonstrated that while variables from age/gender at diagnosis were not predictive, week 12 variables including PCDAI >5 (P = 0.02), CRP >20 mg/L (P = 0.02), and faecal calprotectin >400 µg/g (P = 0.03) as optimal cut-offs were associated with increased risk of relapse. A prediction model for patients in remission including gender, age, week 12 PCDAI, calprotectin and CRP had sensitivity 43%, specificity 92%, PPV 78%, NPV 71% for relapse. Conclusions: Early relapses were associated with a higher risk for disease complications at followup. Relapse prediction based on week 12 disease activity or inflammation is superior to prediction using data from diagnosis.

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