P765 Tolerating infliximab therapeutic drug monitoring without anti-drug antibodies – an argument for drug intolerant assays?
Carlson, S.(1);Evgeniou, V.(1)*;Kok, K.(1);
(1)Royal London Hospital- Barts Health NHS Trust, Gastroenterology, London, United Kingdom;
Background
Therapeutic drug monitoring (TDM) helps guide clinical decision making in IBD patients on infliximab (IFX). There are two types of IFX TDM assays, drug tolerant and intolerant, where drug tolerant assays allow the detection of anti-drug antibodies (ADA) in the presence of drug and the latter does not. Our immunology laboratory is in the process of changing from a drug tolerant to a drug intolerant IFX assay for cost reasons. We aimed to determine whether this switch would affect the management of IBD patients with therapeutic IFX levels and detectable antibodies.
Methods
This was a retrospective cross-sectional study in a central London tertiary hospital. Patients were included if they had a diagnosis of Crohn’s Disease (CD), Ulcerative Colitis (UC), or Indeterminate colitis, and had therapeutic IFX levels (>3mg/ml) with detectable anti-drug antibodies (ADA) (>10 AU/ml) between January 2017 to March 2022. Electronic health records were reviewed to determine clinical actions within 4 months of drug measurement. Actions were categorized into three groups by two gastroenterology physicians: no change to management, ADA dependent or independent actions. ADA dependent decisions were immunomodulator (IMM) addition or discontinuation. ADA independent decisions included switching biologic, stopping IFX, or escalation/de-escalation in IFX dosing.
Results
A total of 2675 IFX TDM tests were performed for IBD patients in the defined period. Of these, 237 patients had 477 TDM results with therapeutic IFX levels and detectable ADA. Baseline characteristics were 36.8% (n=87) female, mean age (y) of 30 (SD ±13), and 66.2% (n=157) had CD. At the time of measurement, 76.1% (n=363/477) of patients were on combination therapy with an IMM and 23.1% (n=110) had active disease on physicians’ global assessment. Changes to management were made in 23.5% (112/477) of clinics following TDM, but only 2.5% (12/477) of actions were ADA dependent. There was no difference in high titer ADA group (>40 AU/ml) compared to low. Variables that significantly affected clinical decisions were IFX dose (p<0.001), IFX interval (p=0.004), and clinical disease activity (p<0.001).
Conclusion
1 in 40 clinical decisions made in patients with therapeutic drug levels and detectable ADAs rely on knowing the ADA level. A cost analysis, with an appropriate IFX drug level threshold under which ADAs would be performed, assessing the proposed switch to a drug intolerant TDM assay would help determine whether cost savings outweigh missed decision-making opportunities.