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

Maria M.E. Jongsma, Martine A. Aardoom, Martinus A. Cozijnsen, Merel Van Pieterson, Tim De Meij, Michael Groeneweg, Obbe F. Norbruis, Victorien M. Wolters, Herbert M. Van Wering, Iva Hojsak, Kaija Leena Kolho, Thalia Hummel, Janneke Stapelbroek, Cathelijne Van Der Feen, Patrick F. Van Rheenen, Michiel P. Van Wijk, Sarah T.A. Teklenburg-Roord, Marco W.J. Schreurs, Dimitris Rizopoulos, Michail DoukasJohanna C. Escher, Janneke N. Samsom, Lissy De Ridder

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Abstract

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).

Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalGut
Volume71
Issue number1
DOIs
Publication statusPublished - 1 Jan 2022

Bibliographical note

Funding Information:
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.

Funding Information:
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).

Publisher Copyright:
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

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