Tu1832 – Association of Vedolizumab Levels with Clinical and Biochemical Markers of Inflammation During Maintenance Therapy in Inflammatory Bowel Disease

Background: Therapeutic drug monitoring helps guide decision making in the treatment of IBD with anti-TNF therapies.Standard ELISA technology is unable to measure antibodies in the presence of drug.Liquid phase assays are also available, and are drug tolerant.The clinical relevance of drug antibodies detected in the presence of drug however is not well characterized.Aims: 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.Methods: A homogeneous mobility shift assay (HMSA) was used to measure infliximab(IFX)/adalimumab(ADA) drug concentration and antibody levels in IBD patients treated with anti-TNF (Prometheus Laboratories).Drug level was compared between samples where 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 Drug+AB+ and Drug+AB-samples.CRP was also compared between Drug+AB+ samples and Drug-AB+ samples.Drug levels and CRP were compared using the Mann-Whitney U test.Where patients had >1 test, duplicate samples were excluded from analyses.Where patients with Drug+AB+ results had subsequent levels performed, we assessed persistence of drug antibodies.Results: 893 samples (501 IFX, 392 ADA) from 572 patients were available for analysis.Following exclusion of duplicates; 46 (8.0%) Drug+AB+, 456 (79.7%)Drug+AB-, 51 (8.9%) Drug-AB+, and 19 Drug-AB-(3.3%).Median IFX level in Drug+AB+ samples was 2.3c ˇg/mL (IQR 1.7-6.7)vs. median IFX level of 13.2cˇg/mL (IQR 6.1-22.3) in Drug+AB-samples (p<0.0001).Median ADA level in Drug+AB+ samples was 6.7cˇg/mL (IQR 3.4-10.2) vs. median ADA level of 14.8c ˇg/mL (IQR 9.9-21.0) in Drug+AB-samples (p<0.0001), Figure 1.CRP results were available for 290 samples.Median CRP for Drug+AB+, Drug+AB-, and Drug-AB+ samples was 5.3mg/L (IQR 1.9-11.8),2.4mg/L (IQR 0.8-8.4), and 3.7mg/L (IQR 2.0-10.9)respectively.CRP in the Drug+AB+ group did not differ significantly from Drug+AB-or Drug-AB+ groups, p= 0.10 and p=0.93.21 patients with Drug+AB+ samples had a subsequent assay.Median interval to most recent follow up assay was 305 days .11(52.4%) had persistent drug antibodies, whilst 10(47.6%)had negative antibodies.Conclusion: IFX and ADA antibodies detected in the presence of drug are associated with significantly lower drug levels, suggesting that such antibodies significantly impact drug pharmacokinetics.Antibodies detected in the presence of drug however are not associated with significant differences in CRP.Almost half of Drug+AB+ patients with subsequent testing showed clearance of antibodies.Thus, it appears that antibodies detected in presence of drug can be overcome.