Noninvasive Targeted Crohn Disease Management by Combining Endoscopic Healing Index and Therapeutic Drug Monitoring

Background and Aims: Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug 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 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 = 1731) 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 mu g/mL and for adalimumab (N = 935): 9.2 vs 5.0 mu g/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 mu g/mL (5-9 mu g/mL in pediatric patients) and for adalimumab: 5-10 mu g/mL (8 mu g/mL in pediatric patients) best discriminated EHI <20 vs > 50. Conclusions: We report the anti-TNF concentration range associated with EHI <20. Combined testing of EHI and TDM is proposed as a noninvasive approach for treat-to-target management which could improve the ability to monitor disease and optimize anti-TNF therapy. Lay Summary In a large clinical cohort of 1731 adult and pediatric patients with Crohn disease, we evaluated the correlation between serum drug concentrations of biologics infliximab or adalimumab and a serum biomarker for mucosal inflammation and propose a noninvasive approach for treat-to-target management to optimize therapy with biologics.