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Oral presentations: Scientific Session 11: What have we got outside our box of drugs? (2020)

OP38 Top-down infliximab superior to step-up in children with Moderate-to-Severe Crohn’s disease: A multicentre randomised controlled trial

M. Jongsma MSc1, M. Aardoom1, M. Cozijnsen1, M. van Pieterson1, T. de Meij2, O. Norbruis3, M. Groeneweg4, V. Wolters5, H. van Wering6, I. Hojsak7, K.L. Kolho8, T. Hummel9, J. Stapelbroek10, C. van der Feen11, P. Rheenen12, M. van Wijk2, S. Teklenburg-Roord3, J. Escher1, J. Samsom13, L. Ridder1

1Department of Pediatric Gastroenterology, Erasmus MC - Sophia Children’s Hospital, Rotterdam, The Netherlands, 2Department of Paediatric Gastroenterology, Amsterdam UMC/Emma Children’s Hospital, Amsterdam, The Netherlands, 3Department of Paediatric Gastroenterology, Isala Hospital, Zwolle, The Netherlands, 4Department of Paediatrics, Maasstad Hospital, Rotterdam, The Netherlands, 5Department of Paediatric Gastroenterology, Utrecht UMC/Wilhelmina Children’s Hospital, Utrecht, The Netherlands, 6Department of Paediatric Gastroenterology, Amphia Hospital, Breda, The Netherlands, 7Department of Paediatric Gastroenterology, Zagreb Children’s Hospital, Zagreb, The Netherlands, 8Department of Paediatric Gastroenterology, Tampere University Hospital and University of Tampere, Helsinki, Finland, 9Department of Paediatric Gastroenterology, Medical Spectrum Twente, Enschede, The Netherlands, 10Department of Paediatric Gastroenterology, Catharina Hospital, Eindhoven, The Netherlands, 11Department of Paediatric Gastroenterology, Jeroen Bosch Hospital, Den Bosch, The Netherlands, 12Department of Paediatric Gastroenterology, UMCG, Groningen, The Netherlands, 13Laboratory of Paediatrics, Erasmus MC - Sophia Children’s Hospital, Rotterdam, The Netherlands

Background

In newly diagnosed paediatric Crohn’s disease (CD) patients current guidelines instruct to start exclusive enteral nutrition (EEN) or oral prednisolone in combination with immunomodulators to achieve remission. Infliximab (IFX) is proven to be highly effective in paediatric CD patients, but mostly used once patients are refractory, the so-called step-up (SU) treatment strategy. However, evidence is emerging IFX is more effective if initiated earlier in the disease course. We investigated whether initiation of IFX directly after diagnosis of moderate-to-severe CD, i.e. top-down (TD) treatment, results in a higher long-term remission rate compared with SU treatment.

Methods

For this international randomised controlled trial (RCT) patients aged 3–17 years, with new-onset, untreated CD with weighted paediatric CD activity index (wPCDAI) >40 were included. TD treatment consisted of 5 IFX (CT-P13) infusions of 5 mg/kg (0, 2, 6, 14, 22 weeks) combined with azathioprine (AZA). After 5 infusions, IFX was stopped while continuing AZA. SU treatment consisted of induction therapy with EEN or oral prednisolone combined with AZA as a maintenance treatment. In both groups, IFX could be (re)started on predefined conditions. The primary endpoint of this study was sustained clinical remission (wPCDAI <12.5) at week 52 without the need for additional therapy or surgery. Secondary endpoints included patient rate using IFX at week 52, mucosal healing (SES-CD <3) and low faecal calprotectin levels (<250 μg/g) at week 10.

Results

100 patients were included in 12 centres. Three out of 100 patients did not start with the study after randomisation (n = 97; 49 TD vs. 48 SU). At 52 weeks, 21/48 (44%) of TD patients were in clinical remission without a need for treatment intensification or surgery, while in the SU group this number was significantly lower (8/48, p = 0.004). After induction therapy, IFX was (re)started in 19/49 (39%) TD patients compared with 30/48 (62%) SU patients within 52 weeks (p = 0.019). At week 10, significantly more TD (27/44, 61%) than SU treated patients (17/44, 39%) were in clinical remission (p = 0.033). Fifty-seven of 97 consented to endoscopy at week 10. Endoscopic remission rates were higher in TD (16/27 [59%], median SES-CD 1 [IQR 0–5]) than SU treated patients (5/30 [17%], median SES-CD 6 [IQR 3–16], p = 0.001). Similarly, low faecal calprotectin levels were more frequent in the TD group (n = 75; TD 21/40 [53%] vs. SU 9/35 [26%], p = 0.027).

Conclusion

We are the first to compare TD IFX to SU treatment in an RCT of paediatric CD patients. TD treatment was superior to SU in achieving sustained clinical remission. Therefore, we advise to start IFX directly after diagnosis in moderate-to-severe paediatric Crohn’s disease patients.