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  • First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn’s disease: an open-label multicentre randomised controlled trial

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Inflammatory bowel disease
Original research
First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn’s disease: an open-label multicentre randomised controlled trial
  1. Maria M E Jongsma1,
  2. Martine A Aardoom1,
  3. Martinus A Cozijnsen1,
  4. Merel van Pieterson1,
  5. Tim de Meij2,
  6. Michael Groeneweg3,
  7. Obbe F Norbruis4,
  8. Victorien M Wolters5,
  9. Herbert M van Wering6,
  10. Iva Hojsak7,8,
  11. Kaija-Leena Kolho9,10,
  12. Thalia Hummel11,
  13. Janneke Stapelbroek12,
  14. Cathelijne van der Feen13,
  15. Patrick F van Rheenen14,
  16. Michiel P van Wijk2,
  17. Sarah T A Teklenburg-Roord4,
  18. Marco W J Schreurs15,
  19. Dimitris Rizopoulos16,
  20. Michail Doukas17,
  21. Johanna C Escher1,
  22. Janneke N Samsom18,
  23. Lissy de Ridder1
  1. 1 Paediatric Gastroenterology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
  2. 2 Paediatric Gastroenterology, University Medical Center Amsterdam—Location VUmc, Amsterdam, The Netherlands
  3. 3 Paediatrics, Maasstad Hospital, Rotterdam, The Netherlands
  4. 4 Paediatrics, Isala Hospital, Zwolle, The Netherlands
  5. 5 Paediatric Gastroenterology, Utrecht Medical Center/Wilhelmina Children's Hospital, Utrecht, The The Netherlands
  6. 6 Paediatrics, Amphia Hospital, Breda, The Netherlands
  7. 7 Referral centre for Paediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Zagreb, Croatia
  8. 8 University JJ Strossmayer, School of Medicine Osijek, Osijek, Croatia
  9. 9 Paediatric Gastroenterology, Children's Hospital, University of Tampere, Helsinki, Finland
  10. 10 Tampere University, Tampere, Finland
  11. 11 Paediatrics, Medical Spectrum Twente, Enschede, The Netherlands
  12. 12 Paediatrics, Catharina Hospital, Eindhoven, The Netherlands
  13. 13 Paediatrics, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
  14. 14 Paediatric Gastroenterology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
  15. 15 Immunology, Erasmus MC, Rotterdam, The Netherlands
  16. 16 Biostatistics, Erasmus MC, Rotterdam, The Netherlands
  17. 17 Pathology, Erasmus MC, Rotterdam, The Netherlands
  18. 18 Laboratory of Pediatrics, Division of Gastroenterology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
  1. Correspondence to Dr Lissy de Ridder, Pediatric Gastroenterology Department, Erasmus MC Sophia Children Hospital, 3000 CA Rotterdam, The Netherlands; l.deridder{at}erasmusmc.nl

Abstract

Objective In newly diagnosed paediatric patients with moderate-to-severe Crohn’s disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment.

Design In this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3–17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI <12.5 at week 52, without need for treatment escalation, using intention-to-treat analysis.

Results 100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was not significantly different (p=0.421). However, 19/46 (41%) patients in the FL-IFX group were in clinical remission on azathioprine monotherapy without need for treatment escalation vs 7/48 (15%) in the conventional group (p=0.004).

Conclusions FL-IFX was superior to conventional treatment in achieving short-term clinical and endoscopic remission, and had greater likelihood of maintaining clinical remission at week 52 on azathioprine monotherapy.

Trial registration number ClinicalTrials.gov Registry (NCT02517684).

  • inflammatory bowel disease
  • paediatric gastroenterology
  • IBD clinical
  • infliximab

Data availability statement

No data are available. The data that support the findings of this study are available from the corresponding author, upon reasonable request.

https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/gutjnl-2020-322339

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    Data availability statement

    No data are available. The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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    Footnotes

    • Twitter @PFvRheenen, @LissydeRidder

    • Contributors LdR, JS and MAC contributed to the study concept and design. LdR and MMEJ had full access to the data in the trial and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to acquisition, analysis or interpretation of the data. MMEJ, MAA, JNS, JCE and LdR contributed to drafting of the manuscript. All authors contributed to critical revision of the manuscript and provided important intellectual content. DR and MMEJ contributed to the statistical analysis. LdR supervised the study. All authors approved the final version of this manuscript.

    • Funding This trial was supported by ZonMw (The Netherlands Organisation for Health Research and Development) under project number 113202001, Crocokids (a Dutch fundraising organisation to support research on IBD in children) and an Investigator-Sponsored Research Award from Pfizer (Study ID WI213008).

    • Disclaimer The funders of the study had no role in the study design, data collection, statistical analysis, interpretation or writing of the report. The corresponding author had full access to the study data and had final responsibility for the content of the manuscript and decision to submit for publication.

    • Competing interests LdR reports grants from ZonMW, ECCO, Crocokids and Pfizer and consultancy fees from Abbvie, during the conduct of the study. MAA received a consultant fee from Abbvie, outside the submitted work. MAC reports grants from ZonMw and Crocokids, and grants and non-financial support from Pfizer during the conduct of the study. IH received a payment/honorarium for lectures from BioGaia, Nutricia, Oktal pharma, Nestle, Biocodex and AbelaPharm. K-LK received consultant fees from Abbvie, Biocodex, Ferring, MSD and Tillotts Pharma, and research grants from the Pediatric Research Foundation (Finland) and the Helsinki University Research Fund, outside the submitted work. TH received a consultant fee from Pfizer, outside the submitted work. JS reports personal fees from Nutricia, outside the submitted work. MPvW reports personal fees from Danone and Laborie, outside the submitted work. STAT-R received a consultant fee from Pfizer, outside the submitted work. JCE received consultant fees from Abbvie and Janssen, as well as research support from MSD and Nutricia.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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