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P382 Combination therapy with TNF-inhibitors and immunomodulators are associated with shorter duration to first serious infection: the DEVELOP experience

J. Escher*1, B. Gold2, J. Izanec3, C. Busse4, Y. Wang5, S. Cucchiara6

1Erasmus MC-Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands, 2GI Care for Kids and Emory University Hospital, Atlanta, USA, 3Janssen Scientific Affairs, LLC, Horsham, USA, 4Janssen Pharmaceuticals, Horsham, USA, 5Janssen Research and Development, LLC, Spring House, USA, 6Sapienza University of Rome, Rome, Italy

Background

DEVELOP is a multi-centre, international, prospective, observational registry of the long-term safety and clinical status of 6070 paediatric patients with inflammatory bowel disease (IBD) diagnosed prior to 18 years of age who were treated with anti-tumour necrosis factor biologics (aTNF) and/or other medical therapies for IBD. Our aim was to assess the risk factors that lead to first serious infection (SI): an infection requiring hospitalisation and/or IV therapy.

Methods

Physicians participating in the registry prescribe IBD treatments based on their usual clinical practice and standards of care. Patients are categorised into cohorts according to their IBD medication exposure representing prevalent or incident exposure. The registry started enrolment in 2007 and completed enrolment in 2017. After the initial enrolment visit, data are obtained by the registry physician or designee every 6 months. SI data includes infections that occurred within 91 days of exposure to aTNF relative to non-biologics. The most recent available data cut (30 June 2018) includes 33586 patient-years (PY) of follow-up in the registry.

Results

The analysis of the stepwise Cox regression model for time to first SI among aTNF only patients relative to the non-biologics cohort included 3,566 Crohn’s disease (CD) patients and 1063 ulcerative colitis (UC) patients who had at least 1 post-baseline follow-up visit, complete baseline covariate data, and complete disease severity data at event. Results of this analysis are seen in Table 1. In CD patients, combination therapy with aTNF/IMM, monotherapy with aTNF or CS, disease severity (hazard ratio [HR] 3.193), recent hospitalisation, gender, length of diagnosis and geographic region were all significantly associated with shorter duration of time to first SI. In UC patients, monotherapy with aTNF or CS (HR 3.913), combination therapy with aTNF and IMM, disease severity and recent hospitalisation were significantly associated with shorter duration of time to first SI.

Conclusion

In both CD and UC patients, combination therapy with aTNF and IMM was significantly associated with shorter time to first SI, as was monotherapy with CS or aTNF, disease severity and recent hospitalisation. Monotherapy with IMM was not associated with shorter duration in either disease state. Disease severity was the strongest predictor by hazard ratio in the CD cohort while CS use was the strongest predictor in the UC cohort.

Abstract P382 – Table 1. Cox proportional hazards model analysis to evaluate risk factors (including Anti-TNF Biologics, using exposure within 91 days) associated with time to first serious infection