A26 USE OF DRUG-TOLERANT ASSAYS IN INFLAMMATORY BOWEL DISEASE; WHAT DOES IT TELL US?

Therapeutic drug monitoring helps guide decision making in the treatment of IBD with anti-TNF therapies. Unlike older assays, newer drug-tolerant assays (such as the Prometheus assay) enable detection of drug antibodies in the presence of drug. The clinical relevance of drug antibodies detected in the presence of drug however is poorly understood. To assess the clinical relevance of antibodies to infliximab and adalimumab detected in the presence of drug. In particular, to assess the association of such antibodies with drug levels and CRP. The Prometheus assay was used to measure infliximab(IFX)/adalimumab(ADA) drug concentration and antibody levels in IBD patients treated with anti-TNF. Drug level was compared between samples whereby both drug and antibody were detectable (Drug+AB+), vs. samples with detectable drug and negative antibodies (Drug+AB-). Where CRP was assessed contemporaneously, CRP was compared between samples with detectable drug and antibody (Drug+AB+) vs. Drug+AB- samples. CRP was also compared between Drug+AB+ samples and Drug-AB+ samples. Where patients with detectable antibodies (either Drug+AB+ or Drug-AB+) had a subsequent test performed, we compared persistence of drug antibodies; Drug+AB+ vs. Drug-AB+. For each analysis, where patients had >1 relevant sample, only the earliest sample was used for analysis. 913 samples (511 IFX, 402 ADA) from 564 patients were analysed. Median IFX level in Drug+AB+ samples was 3.8μg/mL (IQR 1.7–8.6) vs. median IFX level of 13.2μg/mL (IQR 6.5–23.1) in Drug+AB- samples; p<0.0001. Median ADA level in Drug+AB+ samples was 7.5μg/mL (IQR 3.4–10.5) vs. median ADA level of 14.7μg/mL (IQR 10.1–21.0) in Drug+AB- samples; p<0.0001 (Mann-Whitney U test). CRP results were available for 345 samples. Median CRP for Drug+AB+, Drug+AB-, and Drug-AB+ samples was 3.2mg/L (IQR1.8–14.1), 2.5mg/L (IQR 0.8–8.3), and 4.6mg/L (IQR 2.4- 19.3) respectively. CRP in the Drug+AB+ group did not differ significantly from Drug+AB- or Drug-AB+ groups, p=0.10 and p=0.39 (Mann-Whitney U test). 32 patients who had antibodies detected (22 Drug+AB+ and 10 Drug-AB+) had a subsequent assay. 12(54.5%) Drug+AB+ and 9(90%) Drug-AB+ patients had persistent drug antibodies on their subsequent test; p=0.11 (Fisher’s exact test). IFX and ADA antibodies detected in the presence of drug are associated with lower drug levels, suggesting that such antibodies significantly impact drug pharmacokinetics. Antibodies detected in the presence of drug however are not associated with differences in CRP. Persistence of antibodies over time was evident in a lesser proportion of Drug+AB+ patients vs. Drug-AB+ patients. Whilst this finding failed to reach statistical significance, this may have been due to insufficient patient numbers to adequately power this aspect of our study. Drug assays funded by Prometheus

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