Non-Invasive Targeted Crohn’s Disease Management by Combining Endoscopic Healing Index and Therapeutic Drug Monitoring

Abstract

Abstract Background & Aims Therapeutic drug monitoring (TDM) with measurement of serum drug and anti-drug antibody concentrations is used to optimize tumor necrosis factor antagonists (anti-TNF). The endoscopic healing index (EHI) is a validated serum-based assay to measure mucosal inflammation in adults with Crohn’s disease (CD). Our objectives were to evaluate the relationship between EHI and TDM results, and to determine the anti-TNF concentration range associated with EHI<20 (consistent with endoscopic remission) Methods Adult and pediatric patients with CD (N=1,731) were selected retrospectively from a clinical laboratory cohort. Patients were selected if they had an ICD-10 code for CD and if results for EHI and TDM were available within 30 days of each other. The relationship between EHI and TDM results was examined and the anti-TNF concentration range associated with EHI<20 vs. >50 was evaluated Results Median anti-TNF concentration was higher in patients with EHI<20 vs. >50 for infliximab (N=796): 11.1 vs. 3.4 µg/ml and for adalimumab (N=935): 9.2 vs. 5.0 µg/ml (p<0.0001 both drugs). Patients with antibodies to infliximab (12.8%) or adalimumab (14.9%) had lower anti-TNF concentrations (p<0.001 both drugs) and higher EHI (p<0.01 both drugs). The concentration range for infliximab: 5-15 µg/ml (5-9 µg/ml in pediatric patients) and for adalimumab: 5-10 µg/ml (8 µg/ml in pediatric patients) best discriminated EHI<20 vs. >50 Conclusion We report the anti-TNF concentration range associated with EHI<20. Combined testing of EHI and TDM is proposed as a non-invasive approach for treat-to-target management which could improve the ability to monitor disease and optimize anti-TNF therapy.