Program and Abstracts from the Canadian Digestive Diseases Week ™ 2016

Abstract

A247: Concentrations of 6-Thioguanine Nucleotide Correlate with Infliximab and Adalimumab Levels in Patients with Inflammatory Bowel Disease on Combination Therapy A. Trajkovski, 247.1 O. Kelly, 247.1 A. Weizman, 247.1 G. Nguyen, 247.2 H. Steinhart, 247.1 M. Silverberg, 247.1 and K. Croitoru 247.1 Author information Copyright and License information Background. Combining immunomodulators with anti-TNF (tumour necrosis alpha) therapy in Inflammatory Bowel Disease (IBD) is associated with higher drug levels and mucosal healing. Optimal thiopurine dosing remains unclear. Recent data suggest correlation between 6-Thioguanine (6TG) and infliximab (IFX) levels. Aims. We examined if this correlation extended to Adalimumab (ADA) levels and associations with mucosal healing. Methods. A cross-sectional study of IBD patients receiving combination therapy (IFX/ADA + thiopurine) was performed. Patients with simultaneous anti-TNF level/antibody (ADA/IFX; Prometheus assay) and thiopurine metabolite testing (6TG + MMP) were included. Endoscopic remission was defined as Mayo <1 (Ulcerative colitis; UC) and SESCD < 3 (Crohn's disease; CD). Primary outcomes were anti-TNF level and antibody to anti-TNF and were analyzed as continuous and dichotomized variables with calculated IFX/ADA cutoff values best predicting mucosal healing. 6TG levels were examined as continuous and in quartile distribution (1: 0–124; 2: 125–250; 3: 251–400; 4: >400 pmol/8 × 108 RBC). Results. 64 patients on combination were included (34 ADA, 30 IFX). Gender, age, phenotype and treatment duration were not significantly different between groups. ADA group had greater endoscopic activity (70% versus 55%, p = 0.01). Mean 6TG (326, p = 0.84) and MMP levels (1572, p = 0.07) were similar. Mean IFX and ADA levels were higher in combination therapy compared to a monotherapy cohort (12.3 versus 10.2 $μ$g/mL IFX, p = 0.04, 11.4 versus 9.8 $μ$g/mL ADA, p = 0.04). There was a trend toward lower antibodies (2.6 versus 7.9 U/mL IFX, 3.5 versus 6 U/mL ADA) compared to monotherapy (p = 0.26, 0.35). Higher anti-TNF levels were associated with endoscopic remission. Anti-TNF levels inversely correlated with Mayo score (r = −0.69, p = 0.008, AUC 0.6 [0.46–0.83]) and SESCD (r = −0.4, p = 0.039, AUC 0.64 [0.48–0.83]). 6TG levels were associated with higher anti-TNF levels. Based on ROC, using a cutoff IFX >7.6 (sens. 82% spec. 62%), 6TG >125 was associated with attaining clinically adequate IFX levels (p = 0.001, r = 0.49, Fishers exact p = 0.018). Using a cut off of >6.6, (sens. 83%, spec. 54%), 6TG >125 correlated with clinically adequate ADA levels (r = 0.58, p = 0.001, Fishers exact p = 0.009). 6TG values in quartiles(Q)2 and 3 (125–400) were associated with therapeutic anti-TNF levels (p = 0.001) and endoscopic healing (p = 0.001). Antibody presence was associated with endoscopic activity (p = 0.05). 6TG levels in Q2 and 3 had fewer antibodies but did not reach significance. Conclusions. 6TG levels >125 pmol/8 × 108 RBC correlate with therapeutic IFX/ADA levels and endoscopic remission. Funding Agencies: CAG, CIHR, Prometheus Laboratories provided Infliximab and Adalimumab level and antibody testing