Tu1315 Loss of Response in IBD Patients on Infliximab Treatment: Assay of Infliximab Trough Levels and Total Antibodies to Infliximab

Abstract

Optimization of infliximab therapy in inflammatory bowel disease (IBD) patients who lose the clinical response is currently performed empirically. The assay of antibodies to infliximab (ATI) and infliximab trough levels (TL) could be helpful in the clinical decision. We collected sera from 102 IBD patients who were in maintenance treatment with infliximab. Fifty-five patients had experienced a loss of response (LOR) and most of them (45/55) had their infliximab dose already been optimized at 7.5 to 10 mg/kg. As a control group we studied 47 patients in stable clinical response. Blood was drawn for ATI, TL and C-reactive protein (CRP) assay immediately before the next infliximab infusion. We assayed ATI and TL by an ELISA kit (Immundiagnostik AG, Bensheim, FRG) that measures both free and bound antibodies even in the presence of circulating in fliximab. ATI results were expressed as arbitrary units (AU)/ml. TL were expressed as ug/ml. The subsequent clinical decisions were made blinded to ATI and TL levels. Clinical activity and CRP were also assessed after 12 months. Fifty-one patients had Crohn's disease and 51 had ulcerative colitis. Twenty-three were on concomitant immune modulators. In the whole patient population, median ATI were 24,5 AU/ml (IQR 7,4 to115,8) while median TL were 2,3 ug/ml (IQR 0 to 5,6). ATI and TL were negatively correlated (Spearman's rho -0,579, p 2,08 ug/ml for predicting clinical response at 12 months with 56,4% sensitivity and 70,8% specificity (AUC 0,628, 95% CI 0,527 to 0,722, p= 0,038). Among patients with LOR, 62% had ATI > 26,3 AU/ml, as compared to 32% of those maintaining the response (p=0,003 by Fisher's exact test). A significant correlation was detected between ATI and CRP levels both at baseline (Spearman's rho 0,218, p= 0,0287) and after 12 months (rho 0,284, p= 0,0043). Prospective studies will determine the utility of these cut off values in the management of LOR to infliximab in IBD.