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P326 Audit and review of infliximab therapeutic drug monitoring and prescribing practices in paediatric inflammatory bowel disease (IBD) patients

C. Lang*1

1Our Lady's Children's Hospital Crumlin, Pharmacy, Dublin, Ireland

Background

Infliximab (IFX) is a monoclonal antibody against TNF-α which is implicated in the inflammatory response of IBD. Despite its success a large proportion of patients experience loss of response (LOR). This is a big concern, especially in children where treatment options are more limited. Therapeutic drug monitoring (TDM) has been proposed as a way of identifying patients at risk of LOR, as it is associated with sub-therapeutic IFX levels and the presence of antibodies to IFX (ATIs). IFX TDM was introduced to optimise IBD outcomes.

The objectives of this study were to audit whether all IBD patients on IFX had proactive TDM at the end of IFX induction (ie, fourth infusion), evaluate the IFX TDM results and examine how these influenced prescribing.

Methods

Sixty-three IBD patients were initiated on IFX in 2016 and 2017. Forty-five patients were included. Excluded were patient’s still undergoing induction or had a delay, dose increase or discontinued IFX during induction. Recorded were IFX levels, ATI levels, IBD disease type, IFX induction regimen and changes to therapy in response to TDM.

Results

IFX TDM was performed in 39/45 (86%) patients at the fourth IFX infusion.

The majority of patients 31/45 (69%) had standard induction (5 mg/kg at Weeks 0,2,6,14), 9/45 (20%) had escalated induction (5 mg/kg at Weeks 0, 2, 6, 12) and 5/45 (11%) had rapid induction (5 mg/kg at weeks 0,1,4,8/12). The review demonstrated that 30/39 (77%) patients had suboptimal IFX levels (<4 mg/l), 5/39 (13%) patients achieved therapeutic IFX levels (4–8 mg/l), and 4/39 (10%) patients had high IFX levels (>8 mg/l). Patients were more likely to achieve therapeutic IFX levels with escalated induction compared with standard induction, 37% compared with 8%. ATI’s were detected in 10/39 (26%) patients. All of these patients also had low or undetectable IFX levels suggesting that low IFX levels are a primary driving factor for the development of ATIs. In response to TDM results 32/39 (82%) patients required a change in therapy. Of these 29/32 (90%) required IFX optimisation which is defined as an increase in dose to 10 mg/kg (44%), decrease in dosage interval to 6 weekly (38%) or both (8%). Two patients switched therapy (6%) and 1 discontinued IFX and had a colectomy (3%).

Conclusion

Our results demonstrate that TDM is helping to identify patients at risk of LOR. A high proportion of patients have sub-therapeutic IFX levels and the presence of ATI’s after IFX induction. These results strongly suggest that standard induction is unsuitable for paediatric IBD patients. Further work is needed to explore an optimum induction regimen.

Clinicians are optimising IFX therapy in response to TDM. Further work is necessary to explore the impact of IFX dose optimisation on disease outcomes.