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P446 Dose escalation with originator infliximab is more common than standard dosing in paediatric IBD: the DEVELOP experience

J. Escher*1, M. Dubinsky2, J. Izanec3, C. Busse3, Y. Wang4, A. Griffiths5

1Erasmus Mc-Sophia Children's Hospital, Rotterdam, The Netherlands, 2Icahn School of Medicine, Mount Sinai, New York, USA, 3Janssen Scientific Affairs, LLC, Horsham, USA, 4Janssen Research and Development, LLC, Spring House, USA, 5The Hospital for Sick Children, University of Toronto, Toronto, Canada

Background

DEVELOP is a multi-centre, prospective, observational registry of the long-term safety and clinical status of 6070 paediatric patients with inflammatory bowel disease (IBD; Crohn’s disease [CD]: 4122, ulcerative colitis [UC]: 1643, and IBD-unclassified[IBD-U]: 305; median age at enrolment 13.0 years) treated with originator infliximab (REM) and/or other medical therapies for IBD as part of routine clinical care. DEVELOP has sites in the US, Canada and the EU and enrolled patients from 2007 to 2017. The labelled maintenance dose and interval of REM for treatment of paediatric CD or UC is 5 mg/kg IV every 8 weeks. Our aim was to assess how frequently providers needed to escalate this dose.

Methods

Enrolment was targeted such that half of the enrolled patients had been exposed to REM at baseline. The treating physicians then continue to prescribe IBD treatments based on their usual clinical practice and standards of care. Patients are categorised into cohorts according to their prevalent or incident IBD medication exposure, including patients receiving therapy prior to enrolment and patients receiving therapy during registry follow-up. The last data cut available (30 June 2018) assessed 33586 patient-years (PY) of follow-up.

Results

Among all patients (Table 1), the median average maintenance dose of REM thus far during the registry period is 6.5 mg/kg (CD: 6.1 mg/kg, UC: 7.5 mg/kg and IBD-U: 8.0 mg/kg). In the most recent 12-month follow-up period, the median maintenance dosing frequency was 8 weeks for CD patients, 7 weeks for UC patients and 6 weeks for IBD-U patients. The median total number of REM infusions was 17.0, with a median duration of REM exposure of 32.3 months and a mean duration of 38.9 months. During the entire registry follow-up period, 27% of patients who had been receiving REM discontinued the drug. The median interval between first dose and discontinuation was 20.9 months and the most common reasons for discontinuation were loss of efficacy (47% of discontinuations), adverse events (17%) and administration reactions (13%).

Conclusion

In the international DEVELOP paediatric IBD registry, standard dosing of REM is the exception rather than the rule. The median maintenance doses used in CD, UC and IBD-U are all higher than the labelled dose of 5 mg/kg. In UC and IBD-U, the median maintenance interval is also shorter than the labelled interval of q8 weeks. Further analysis will examine clinical measures before and after dose escalation.

Table 1. Remicade exposure during registry participation: all IBD patients