491 Prediction of Clinical Response and Mucosal Healing At One Year by Faecal Calprotectin Assay After Induction With Anti-TNF Alpha Agents in IBD Patients

Abstract

BACKGROUND: Measurement of antibodies to infliximab (ATI) and the correlation observed between serum drug concentration and disease status have provided both insight into infliximab (IFX) immunogenicity and clinical utility to these markers for managing IBD patients on IFX. For adalimumab, such data are not readily available nor is clinical utility known. The prevalence of antibodies to adalimumab (ATA) in IBD patients is sparsely reported outside of one company sponsored clinical trial (2.6%). Correlation between ATA/ drug concentration and objective markers of inflammation (CRP) as well as clinical symptoms is poorly described. METHODS: An independent investigator-initiated cross-sectional study prospectively recruited 54 IBD patients on ADA (2 with ulcerative colitis) from a tertiary center to determine 1) prevalence of detectable ATA and drug concentration; 2) correlation between ATA /drug concentration and an objective measure of inflammation, C-reactive protein (CRP); and 3) whether stratified category of ATA/ drug concentration correlated with patient's self-described symptoms (remission, response, active flare). Patients were approached based on use of ADA for Crohn's or ulcerative colitis and not clinical status (remission, response, active). Questionnaire of symptoms, IBD history, ADA dosing, weight and CRP measurement were conducted within two weeks of ATA/drug concentration measurement. ATA/drug concentration blood draw was performed at trough, just prior to next ADA dose, and processed by Prometheus Laboratories. Detectable ATA was defined as .= 1U/ml and detectable drug as .=1 mcg/ml. RESULTS: The prevalence of detectable ATA was 22.2% (n=12/54) and detectable ADA concentration was 90.7% (n=49/54). Serum concentration of ,5 mcg/ml of ADA was associated with an elevated CRP (p=0.001). Detectable ATA was positively associated with an elevated CRP, and notably this correlation was independent of drug concentration (p=0.002) (Figure). Stratification of patients based on ATA/drug concentration demonstrated more active disease in patients with low drug concentration (,5 mcg/ml) and/or detectable ATA (p=0.01). CONCLUSION: Antibodies to adalimumab in ADA-treated IBD patients are more prevalent than reported in clinical trials and almost all patients on ADA have a detectable drug concentration. Both detectable ATA and ADA drug concentration ,5 mcg/ml have an important association with increased inflammation. The observation that detectable ATA correlates with elevated CRP independent of drug concentration is a novel finding and suggests preventing ATA may be the more critical of the two variables to address for maximizing clinical efficacy. That detectable ATA/ low drug concentration correlates with active disease suggests there may be clinical utility in obtaining these measurements, however longer-term data are needed.